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Clinical Trial Results:
Trial of Optimal Therapy for Pseudomonas Eradication in Cystic Fibrosis

Summary
EudraCT number	2009-012575-10
Trial protocol	GB SE IT
Global end of trial date	10 Apr 2018

Results information
Results version number	v1(current)
This version publication date	10 Apr 2019
First version publication date	10 Apr 2019
Other versions
Summary report(s)	Protocol Amendments V2.0, V4.0 and V6.0

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

CH/2007/2661

ISRCTN number

ISRCTN02734162

US NCT number

WHO universal trial number (UTN)

Other trial identifiers

Funder reference: HTA 07/51/01

Sponsor organisation name

University Hospitals Bristol NHS Foundation Trust

Sponsor organisation address

Bristol Royal Children's Hospital, Upper Maudlin Street, Bristol, United Kingdom, BS2 8BJ

Public contact

Ashley Jones, Clinical Trials Research Centre, University of Liverpool, +44 151 795 8751, ctrcqa@liverpool.ac.uk

Scientific contact

Ashley Jones, Clinical Trials Research Centre, University of Liverpool, +44 151 795 8751, ctrcqa@liverpool.ac.uk

Sponsor organisation name

University of Liverpool

Sponsor organisation address

Research Support Office, 2nd Floor Block D, Waterhouse Building, 3 Brownlow Street, Liverpool, United Kingdom, L69 3GL

Public contact

Ashley Jones, Clinical Trials Research Centre, University of Liverpool, +44 151 795 8751, ctrcqa@liverpool.ac.uk

Scientific contact

Ashley Jones, Clinical Trials Research Centre, University of Liverpool, +44 151 795 8751, ctrcqa@liverpool.ac.uk

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

27 Sep 2018

Is this the analysis of the primary completion data?

Yes

Primary completion date

10 Apr 2018

Global end of trial reached?

Yes

Global end of trial date

10 Apr 2018

Was the trial ended prematurely?

Main objective of the trial

This trial assessed whether fourteen days intravenous ceftazidime with tobramycin is superior to three months (12 weeks) oral ciprofloxacin. Both treatment regimes were in conjunction with three months (12 weeks) nebulised colistin. Primary outcome: Successful eradication of P. aeruginosa infection at three months (12 weeks) after allocated treatment had started, remaining infection free through to 15 months (60 weeks) after the start of allocated treatment.

Protection of trial subjects

There were no formal accountability measures required for the trial. TORPEDO-CF has put the following measures in place to safeguard the safety of trial participants: - Participant completed treatment diaries to record treatment compliance - Collection of unused trial IMP - Collection of packaging of used IMP - Verbal interview conducted by the PI at the 3 month follow-up visit - Local procedures should be used if a manufacturer issues a recall

Background therapy

Participants recruited into the study were randomised to one of the following treatment arms: Arm A: 14 days* intravenous (IV) antibiotics as follows: - Ceftazidime 150 milligram (mg)/kilogram (kg)/day, in 3 divided doses (maximum of 3 grams (g) three times daily (tds)). Some centres used a once daily continuous infusion (where the maximum daily dose would usually be 6g/day) or twice daily regimen for ceftazidime. These centres continued to use this regimen for the study and followed their local dosing guidelines. - Tobramycin 10mg/kg/day once daily (od) (maximum 660mg /day). Some centres used a twice daily or three times daily regimen for tobramycin. These centres continued to use their current regimen for the study and should follow their local dosing guidelines. Therapeutic drug monitoring should be used to guide tobramycin dosing as per national guidelines (https://www.cysticfibrosis.org.uk/media/82010/CD_Antibiotic_treatment_for_CF_May_09.pdf) and usual clinic procedures. *Recommended treatment duration should be 14 days, minimum treatment duration should be no less than 10 days Arm B: 3 months oral ciprofloxacin twice daily (bd). (Ciprofloxacin dose will be 20 mg/kg twice daily (maximum 750mg twice daily. This is in line with the BNF for children (http://bnfc.org/bnfc/). Some clinicians prefered to use a lower dose of 15mg/kg twice daily for children under 5 years, as used in national CF guidelines (https://www.cysticfibrosis.org.uk/media/82010/CD_Antibiotic_treatment_for_CF_May_09.pdf). Both treatment arms received 3 months#of nebulised colistin in conjunction to the randomised treatment. Colistin dose was as recommended by the UK CF Trust: 1,000,000 units twice daily for children aged ≤ 2 years and 2,000,000 units twice daily for children aged > 2 years and adults. If the colistin was administered via an I-neb a lower dose of 1,000,000 units twice daily for all ages should be used.

Evidence for comparator

The rationale for choosing fourteen days of intravenous treatment and for choosing three months for oral treatment is that both of these are standard practice for many UK CF centres identified in the HTA feasibility study and both are standard recommendations within the published UK guideline and believed to represent current best practice.

Actual start date of recruitment

18 Jun 2010

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 284

Country: Number of subjects enrolled

Italy: 2

Worldwide total number of subjects

286

EEA total number of subjects

286

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

161

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

60 UK based centres and 1 centre based in Italy took part in the trial. The first patient was randomised on 5th October 2010 and the last patient was randomised on 27th January 2017.

Screening details

There were 1522 screenings from 1308 patients for eligibility and of those 554 were ineligible, 193 were not approached, 489 didn't provide consent and 3 patients were excluded but no reason was given. 286 patients were randomised into the trial. (Note that patients could be screened more than once)

Period 1 title

Baseline

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Blinding implementation details

Randomisation lists were generated in a 1:1 ratio using simple block randomisation with random variable block lengths. Factors within the protocol that were used to stratify randomisation were not disclosed to prevent prediction in this open trial.

Are arms mutually exclusive

Yes

Intravenous (IV) antibiotics

Arm description

14 days IV antibiotics; Ceftazidime and Tobramycin alongside three months of nebulised Colistin

Arm type

Experimental

Investigational medicinal product name

Ceftazidime

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Ceftazidime 150 milligram (mg)/kilogram (kg)/day, in 3 divided doses (maximum of 3 grams (g) three times daily (tds)). Some centres used a once daily continuous infusion (where the maximum daily dose would usually be 6g/day) or twice daily regimen for ceftazidime.

Investigational medicinal product name

Tobramycin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Tobramycin 10mg/kg/day once daily (od) (maximum 660mg /day). Some centres used a twice daily or three times daily regimen for tobramycin.

Investigational medicinal product name

Colistin

Investigational medicinal product code

Other name

Pharmaceutical forms

Nebuliser solution

Routes of administration

Inhalation use

Dosage and administration details

3 months (12 weeks) of nebulised colistin in conjunction to the randomised treatment. Colistin dose was as recommended by the UK CF Trust: 1,000,000 units twice daily for children aged ≤ 2 years and 2,000,000 units twice daily for children aged > 2 years and adults. If the colistin is administered via an I-neb a lower dose of 1,000,000 units twice daily for all ages was used.

Oral antibiotic therapy

Arm description

3 months (12 weeks) of oral ciprofloxacin alongside 3 months (12 weeks) of nebulised colistin.

Arm type

Active comparator

Investigational medicinal product name

Ciprofloxacin

Investigational medicinal product code

Other name

Pharmaceutical forms

Granules and solvent for oral suspension, Tablet

Routes of administration

Oral use

Dosage and administration details

3 months (12 weeks) oral ciprofloxacin twice daily (bd). (Ciprofloxacin dose was 20 mg/kg twice daily (maximum 750mg twice daily. Some clinicians could use a lower dose of 15mg/kg twice daily for children under 5 years, as used in national CF guidelines.

Investigational medicinal product name

Colistin

Investigational medicinal product code

Other name

Pharmaceutical forms

Nebuliser solution

Routes of administration

Inhalation use

Dosage and administration details

Number of subjects in period 1	Intravenous (IV) antibiotics	Oral antibiotic therapy
Started	137	149
Completed	137	148
Not completed	0	1
Unable to obtain PI sign-off	-	1

Period 2 title

Follow-up

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Blinding implementation details

See blinding details for the baseline period.

Are arms mutually exclusive

Yes

Intravenous (IV) antibiotics

Arm description

14 days IV antibiotics; Ceftazidime and Tobramycin alongside three months nebulised Colistin

Arm type

Experimental

Investigational medicinal product name

Ceftazidime

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Tobramycin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Tobramycin 10mg/kg/day once daily (od) (maximum 660mg /day). Some centres used a twice daily or three times daily regimen for tobramycin.

Investigational medicinal product name

Colistin

Investigational medicinal product code

Other name

Pharmaceutical forms

Nebuliser solution

Routes of administration

Inhalation use

Dosage and administration details

Oral antibiotic therapy

Arm description

3 months (12 weeks) of oral ciprofloxacin alongside 3 months (12 weeks) of nebulised colistin.

Arm type

Active comparator

Investigational medicinal product name

Ciprofloxacin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

3 months (12 weeks) oral ciprofloxacin twice daily (bd). (Ciprofloxacin dose was 20 mg/kg twice daily (maximum 750mg twice daily. Some clinicians preferred to use a lower dose of 15mg/kg twice daily for children under 5 years, as used in national CF guidelines.

Investigational medicinal product name

Colistin

Investigational medicinal product code

Other name

Pharmaceutical forms

Nebuliser solution

Routes of administration

Inhalation use

Dosage and administration details

Number of subjects in period 2	Intravenous (IV) antibiotics	Oral antibiotic therapy
Started	137	148
Completed	132	132
Not completed	5	16
Consent withdrawn by subject	1	4
Adverse event, non-fatal	-	1
Other	1	2
Lost to follow-up	3	9

Baseline characteristics

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Reporting group title

Intravenous (IV) antibiotics

Reporting group description

14 days IV antibiotics; Ceftazidime and Tobramycin alongside three months of nebulised Colistin

Reporting group title

Oral antibiotic therapy

Reporting group description

3 months (12 weeks) of oral ciprofloxacin alongside 3 months (12 weeks) of nebulised colistin.

Reporting group values	Intravenous (IV) antibiotics	Oral antibiotic therapy	Total
Number of subjects	137	149	286
Age categorical
PLEASE NOTE THAT THE AGE FOR 3 PARTICIPANTS COULD NOT BE CALCULATED AND THEREFORE DATA WAS UNOBTAINABLE FOR THESE PARTICIPANTS. THE TABLE TITLED 'AGE GROUP BREAKDOWN FOR TRIAL' IN THE SECTION 'TRIAL INFORMATION' HAS THESE 3 PARTICIPANTS ADDED IN THE 'IN UTERO' SECTION TO ALLOW RESULTS TO BE POSTED ONTO EUDRACT. AGE DATA ARE ONLY AVAILABLE FOR 283 PARTICIPANTS IN THE TRIAL.
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	42	28	70
Children (2-11 years)	71	90	161
Adolescents (12-17 years)	18	19	37
Adults (18-64 years)	6	9	15
From 65-84 years	0	0	0
85 years and over	0	0	0
Missing	0	2	2
Not recorded	0	1	1
Gender categorical
Units: Subjects
Female	74	81	155
Male	63	67	130
Not recorded	0	1	1
Pseudomonas status
Units: Subjects
Free	56	55	111
Naïve	81	93	174
Not recorded	0	1	1
Genotype
Units: Subjects
Delta F508/ Delta F508	70	90	160
Delta F508/other	40	43	83
Delta F508/unknown	4	5	9
other/other	12	7	19
Diagnosis not based on genetics	10	3	13
Unknown whether diagnosis based on genetics	1	0	1
Not recorded	0	1	1
Pulmonary exacerbation
Units: Subjects
Yes	18	17	35
No	119	131	250
Not recorded	0	1	1
Candida detected
Units: Subjects
Yes	11	17	28
No	126	131	257
Not recorded	0	1	1
MRSA detected
Units: Subjects
Yes	0	2	2
No	137	146	283
Not recorded	0	1	1
Burkholderia cepacia detected
Units: Subjects
Yes	0	0	0
No	137	148	285
Not recorded	0	1	1
Aspergillus detected
Units: Subjects
Yes	2	2	4
No	135	146	281
Not recorded	0	1	1
Other micro-organism detected
Units: Subjects
Yes	26	31	57
No	111	117	228
Not recorded	0	1	1
BMI z-score (paediatric)
Units: z-score
arithmetic mean (standard deviation)	0.3 ± 1	0.3 ± 0.9	-
BMI (adults)
Units: (m/kg^2)
arithmetic mean (standard deviation)	24.6 ± 1.8	23.2 ± 2.3	-
Time from PsA isolation to treatment initiation
Units: (days)
arithmetic mean (standard deviation)	9 ± 5	7 ± 5	-
%predicted FEV1
Units: FEV1 %predicted
arithmetic mean (standard deviation)	86.6 ± 15.8	85.7 ± 16	-
%predicted FVC
Units: FVC %predicted
arithmetic mean (standard deviation)	92.2 ± 15.5	95.1 ± 14.5	-
%predicted FEF25-75
Units: FEF25-75 %predicted
arithmetic mean (standard deviation)	72.7 ± 26.6	70.6 ± 30.3	-
Oxygen saturation
Units: (%)
arithmetic mean (standard deviation)	97.7 ± 1.4	97.7 ± 1.7	-

End points

Top of page

Reporting group title

Intravenous (IV) antibiotics

Reporting group description

14 days IV antibiotics; Ceftazidime and Tobramycin alongside three months of nebulised Colistin

Reporting group title

Oral antibiotic therapy

Reporting group description

3 months (12 weeks) of oral ciprofloxacin alongside 3 months (12 weeks) of nebulised colistin.

Reporting group title

Intravenous (IV) antibiotics

Reporting group description

14 days IV antibiotics; Ceftazidime and Tobramycin alongside three months nebulised Colistin

Reporting group title

Oral antibiotic therapy

Reporting group description

3 months (12 weeks) of oral ciprofloxacin alongside 3 months (12 weeks) of nebulised colistin.

Primary: Primary efficacy assessment - Successful eradication of P. aeruginosa three months after the start of treatment, remaining infection free through to 15 months after the start of treatment

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End point title

Primary efficacy assessment - Successful eradication of P. aeruginosa three months after the start of treatment, remaining infection free through to 15 months after the start of treatment

End point description

End point type

Primary

End point timeframe

3 months after the start of treatment through to 15 months after the start of treatment .

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	125	130
Units: Subjects
Successful eradication	55	68
Unsuccessful eradication	70	62

Successful eradication from 3 months to 15 months

Statistical analysis description

The number of patients who were classified as (a) a success and (b) failure for the primary outcome (and percentages) were presented for each treatment arm. The relative risk together with 95% confidence interval was reported along with a two-sided p-value from a chi-squared test.

Comparison groups

Oral antibiotic therapy v Intravenous (IV) antibiotics

Number of subjects included in analysis

255

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.184

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

1.09

Primary: Primary efficacy assessment - Successful eradication of P. aeruginosa three months after the start of treatment, remaining infection free through to 15 months after the start of treatment

Top of page

End point title

Primary efficacy assessment - Successful eradication of P. aeruginosa three months after the start of treatment, remaining infection free through to 15 months after the start of treatment

End point description

End point type

Primary

End point timeframe

From 3 months after the start of treatment to 15 months after the start of treatment.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	110	116
Units: Subjects
Successful eradication	97	111
Unsuccessful eradication	13	5

Unsuccessful eradication at 3 months

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

226

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.037

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

2.74

Confidence interval

level

95%

sides

2-sided

lower limit

1.01

upper limit

7.44

Primary: Primary efficacy assessment – Sensitivity analysis 6: no T15 window (Post hoc)

Top of page

End point title

Primary efficacy assessment – Sensitivity analysis 6: no T15 window (Post hoc)

End point description

End point type

Primary

End point timeframe

From 3 months after the start of treatment to 15 months after the start of treatment.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	136	144
Units: Subjects
Successful eradication	58	70
Unsuccessful eradication	78	74

Sensitivity analysis 6

Statistical analysis description

The relative risk with 95% CI was presented. A chi-squared test will be used to calculate a p-value for this relative risk.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

280

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.317

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

1.13

Secondary: Time to reoccurrence of original P.aeruginosa infection - unknown strains assumed to be same as baseline

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End point title

Time to reoccurrence of original P.aeruginosa infection - unknown strains assumed to be same as baseline

End point description

End point type

Secondary

End point timeframe

3 months to 24 months. Only patients who have a baseline sample and at least one sample post three months will be included in this analysis.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	137	148
Units: Subjects
Reoccurence of original P.aeruginosa infection	74	66
Censored	63	82

Time to reoccurrence of original P.aeruginosa

Statistical analysis description

Difference between the two treatment arms was tested using the log-rank test. Cox proportional hazards regression was used to calculate a hazard ratio with 95% CI, comparing the IV treatment group to oral, – unknown strains assumed to be same as baseline.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

285

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.061

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.37

Confidence interval

level

95%

sides

2-sided

lower limit

0.99

upper limit

1.91

Secondary: Time to reoccurrence of original P.aeruginosa infection - unknown strains assumed to be different to baseline

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End point title

Time to reoccurrence of original P.aeruginosa infection - unknown strains assumed to be different to baseline

End point description

End point type

Secondary

End point timeframe

From 3 to 24 months.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	137	148
Units: Subjects
Reoccurence of original P.aeruginosa infection	21	14
Censored	116	134

Time to reoccurrence of original P.aeruginosa

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

285

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.075

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.94

upper limit

3.64

Secondary: Re-infection with a different strain of P.aeruginosa

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End point title

Re-infection with a different strain of P.aeruginosa

End point description

End point type

Secondary

End point timeframe

From baseline to 15 months.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	25	17
Units: Subjects
Same genotype	19	12
Different genotype	6	5

Re-infection with a different strain

Statistical analysis description

The relative risk together with 95% confidence interval was reported along with a two-sided p-value from a chi-squared test.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.733

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

2.25

Secondary: Post hoc analysis – Genotyping results

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End point title

Post hoc analysis – Genotyping results

End point description

End point type

Secondary

End point timeframe

From baseline to 24 months.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	28	22
Units: Subjects
Same genotype	20	13
Different genotype	8	9

No statistical analyses for this end point

Secondary: Lung function - FEV1% predicted

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End point title

Lung function - FEV1% predicted

End point description

End point type

Secondary

End point timeframe

From baseline to 24 months.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	67 ^[1]	70 ^[2]
Units: FEV1% predicted
arithmetic mean (standard deviation)
Baseline	86.6 ± 15.8	85.7 ± 16.0
3 Months (11-13 weeks)	86.3 ± 18.6	81.9 ± 15.6
15 Months (59-62 weeks)	89.5 ± 18.2	82.3 ± 18.9
24 Months (95-97 weeks)	83.8 ± 13.7	79.8 ± 15.0

Notes
[1] - At baseline n=67, T3 n=25, T15 n=32, T24 n= 11
[2] - At baseline n=70, T3 n=28, T15 n=32 , T24 n=17

FEV1 % predicted - 3 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a continuous variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

137

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.008

Method

Mixed models analysis

Parameter type

3 month treatment difference

Point estimate

3.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

6.53

FEV1 % predicted - 15 month treat diff

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

137

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.184

Method

Mixed models analysis

Parameter type

15 month treatment difference

Point estimate

2.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.99

upper limit

5.14

FEV1 % predicted - 24 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures will be fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a continuous variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

137

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.705

Method

Mixed models analysis

Parameter type

24 month treatment difference

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

-3.45

upper limit

5.1

FEV1 % predicted - treat difference

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a continuous variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

137

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.019

Method

Mixed models analysis

Parameter type

treatment difference

Point estimate

3.16

Confidence interval

level

95%

sides

2-sided

lower limit

0.51

upper limit

5.8

Secondary: Lung function - FVC% predicted

Top of page

End point title

Lung function - FVC% predicted

End point description

End point type

Secondary

End point timeframe

From baseline to 24 months.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	67 ^[3]	70 ^[4]
Units: FVC% predicted
arithmetic mean (standard deviation)
Baseline	92.2 ± 15.5	95.1 ± 14.5
3 Months (11-13 weeks)	89.7 ± 19.3	88.9 ± 16.2
15 months (59-62 weeks)	91.4 ± 18.4	89.4 ± 18.8
24 Months (95-97 weeks)	89.4 ± 15.4	91.8 ± 20.4

Notes
[3] - At baseline n=67, T3 n= 25, T15 n=32 and T24 n=11
[4] - At baseline n=70, T3 n=28, T15 n=32 and T24 n=17

FVC % predicted - 3 month treat diff

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

137

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.008

Method

Mixed models analysis

Parameter type

3 month treatment difference

Point estimate

3.86

Confidence interval

level

95%

sides

2-sided

lower limit

1.03

upper limit

6.69

FVC % predicted - 15 month treat diff

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

137

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0396

Method

Mixed models analysis

Parameter type

3 month treatment difference

Point estimate

3.14

Confidence interval

level

95%

sides

2-sided

lower limit

0.15

upper limit

6.14

FVC % predicted - 24 month treat diff

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

137

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.216

Method

Mixed models analysis

Parameter type

24 month treatment difference

Point estimate

2.61

Confidence interval

level

95%

sides

2-sided

lower limit

-1.52

upper limit

6.73

FVC % predicted - treatment difference

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a continuous variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

137

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.009

Method

Mixed models analysis

Parameter type

treatment difference

Point estimate

3.56

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

6.21

Secondary: Lung function - FEF25-75% predicted

Top of page

End point title

Lung function - FEF25-75% predicted

End point description

End point type

Secondary

End point timeframe

From baseline to 24 months.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	44 ^[5]	53 ^[6]
Units: FEF25-75% predicted
arithmetic mean (standard deviation)
Baseline	72.7 ± 26.6	70.6 ± 30.3
3 Months (11-13 weeks)	84.0 ± 23.5	70.6 ± 25.1
15 Months (59-62 weeks)	77.2 ± 28.0	68.1 ± 21.5
24 Months (95-97 weeks)	58.3 ± 23.1	58.9 ± 13.3

Notes
[5] - At baseline n=44, T3 n=18, T15 n=26 and T24 n=7
[6] - At baseline n=53, T3 n=20, T15 n=21 and T24 n=12

FEV25-75% predicted - 3 month treat diff

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.274

Method

Mixed models analysis

Parameter type

3 month treatment difference

Point estimate

3.76

Confidence interval

level

95%

sides

2-sided

lower limit

-2.99

upper limit

10.52

FEV25-75% predicted - 15 month treat diff

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.345

Method

Mixed models analysis

Parameter type

15 month treatment difference

Point estimate

3.46

Confidence interval

level

95%

sides

2-sided

lower limit

-3.74

upper limit

10.66

FEV25-75% predicted - 24 month treat diff

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.505

Method

Mixed models analysis

Parameter type

24 month treatment difference

Point estimate

3.23

Confidence interval

level

95%

sides

2-sided

lower limit

-6.29

upper limit

12.76

FEV25-75% predicted - treatment difference

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a continuous variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.269

Method

Mixed models analysis

Parameter type

treatment difference

Point estimate

3.64

Confidence interval

level

95%

sides

2-sided

lower limit

-2.82

upper limit

10.11

Secondary: Oxygen saturation

Top of page

End point title

Oxygen saturation

End point description

End point type

Secondary

End point timeframe

Baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	118 ^[7]	133 ^[8]
Units: Percentage
arithmetic mean (standard deviation)
baseline	97.7 ± 1.4	97.7 ± 1.7
3 months (11-13 weeks)	97.6 ± 1.5	98.2 ± 1.6
15 months (59-62 weeks)	97.8 ± 1.5	97.9 ± 1.4
24 months (95-97 weeks)	97.9 ± 1.1	97.6 ± 1.8

Notes
[7] - At baseline n=118, T3 n= 42 , t15 n=48 and T24 n=17
[8] - At baseline n=133, T3 n=53, T15 n=46 and T24 n=26

O2 Saturation - 3 month treatment difference

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

251

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.728

Method

Mixed models analysis

Parameter type

3 Month Treatment difference

Point estimate

0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.21

upper limit

0.3

O2 Saturation - 15 month treatment difference

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

251

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.709

Method

Mixed models analysis

Parameter type

15 Month Treatment difference

Point estimate

0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.29

O2 Saturation - Treatment Difference

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a continuous variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

251

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.686

Method

Mixed models analysis

Parameter type

Treatment difference

Point estimate

0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.18

upper limit

0.27

O2 Saturation - 24 Treatment Difference

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

251

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.79

Method

Mixed models analysis

Parameter type

24 month Treatment difference

Point estimate

0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

0.4

Secondary: Growth and nutritional status - Height z-scores

Top of page

End point title

Growth and nutritional status - Height z-scores

End point description

End point type

Secondary

End point timeframe

From baseline to 24 months.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	125 ^[9]	131 ^[10]
Units: Height z-scores
arithmetic mean (standard deviation)
Baseline	-0.4 ± 1.0	-0.4 ± 1.0
3 Months (11-13 weeks)	-0.2 ± 1.0	-0.2 ± 1.0
15 Months (59-62 weeks)	-0.2 ± 1.0	-0.1 ± 0.9
24 Months (95-97 weeks)	-0.5 ± 0.8	-0.7 ± 0.6

Notes
[9] - At baseline n=125, T3 n=32, T15 n=36 and T24 n=13
[10] - At baseline n=131, T3 n=47, T15 n=32 and T24 n=16

Height z-scores - 3 Month Treatment Difference

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

256

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.952

Method

Mixed models analysis

Parameter type

3 Month treatment difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.06

upper limit

0.05

Height z-scores - 15 Month Treatment Difference

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

256

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.572

Method

Mixed models analysis

Parameter type

15 Month treatment difference

Point estimate

-0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.13

upper limit

0.07

Height z-scores - 24 Month Treatment Difference

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

256

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.543

Method

Mixed models analysis

Parameter type

24 Month treatment difference

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.21

upper limit

0.11

Height z-scores - Treatment Difference

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a continuous variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

256

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.939

Method

Mixed models analysis

Parameter type

treatment difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.06

upper limit

0.05

Secondary: Growth and nutritional status - Weight z-scores

Top of page

End point title

Growth and nutritional status - Weight z-scores

End point description

End point type

Secondary

End point timeframe

From baseline to 24 months.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	102 ^[11]	109 ^[12]
Units: Weight z-scores
arithmetic mean (standard deviation)
Baseline	0.0 ± 1.1	0.0 ± 0.9
3 Months (11-13 weeks)	0.2 ± 1.2	0.2 ± 0.9
15 Months (59-62 weeks)	0.1 ± 1.1	0.3 ± 0.8
24 Months (95-97 weeks)	0.1 ± 0.7	-0.4 ± 0.8

Notes
[11] - At baseline n=102, T3 n=30, T15 n=27, T24 n=12
[12] - At baseline n=109, T3 n=37, T15 n=23, T24 n=11

Weight z-scores - 3 Month Treatment Difference

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

211

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.988

Method

Mixed models analysis

Parameter type

3 month treatment difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.06

upper limit

0.06

Weight z-scores - 15 Month Treatment Difference

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

211

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.794

Method

Mixed models analysis

Parameter type

3 month treatment difference

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.15

upper limit

0.11

Weight z-scores - 24 Month Treatment Difference

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

211

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.78

Method

Mixed models analysis

Parameter type

24 month treatment difference

Point estimate

-0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.24

upper limit

0.18

Weight z-scores - Treatment Difference

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a continuous variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

211

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.987

Method

Mixed models analysis

Parameter type

treatment difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.06

upper limit

0.06

Secondary: Growth and nutritional status - BMI z-scores

Top of page

End point title

Growth and nutritional status - BMI z-scores

End point description

End point type

Secondary

End point timeframe

From baseline to 24 months.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	125 ^[13]	131 ^[14]
Units: BMI z-scores
arithmetic mean (standard deviation)
Baseline	0.3 ± 1.0	0.3 ± 0.9
3 Months (11-13 weeks)	0.3 ± 1.0	0.2 ± 1.0
15 Months (59-62 weeks)	0.4 ± 1.1	0.2 ± 1.1
24 Months (95-97 weeks)	0.5 ± 0.7	0.0 ± 0.8

Notes
[13] - At baseline n=125, T3 n=32, T15 n=36 and T24 n=13
[14] - At baseline n=131, T3 n=47, T15 n=32 and T24 n=16

BMI z-score - 3 Month Treatment Difference

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

256

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.767

Method

Mixed models analysis

Parameter type

3 Month Treatment Difference

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.08

upper limit

0.06

BMI z-score - 15 Month Treatment Difference

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

256

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.912

Method

Mixed models analysis

Parameter type

15 Month Treatment Difference

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.14

upper limit

0.16

BMI z-score - 24 Month Treatment Difference

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

256

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.854

Method

Mixed models analysis

Parameter type

24 Month Treatment Difference

Point estimate

0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.22

upper limit

0.26

BMI z-score - Treatment Difference

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a continuous variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

256

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.774

Method

Mixed models analysis

Parameter type

Treatment Difference

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.08

upper limit

0.06

Secondary: Growth and nutritional status - BMI

Top of page

End point title

Growth and nutritional status - BMI

End point description

End point type

Secondary

End point timeframe

From baseline to 24 months.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	7 ^[15]	10 ^[16]
Units: m/kg^2
arithmetic mean (standard deviation)
Baseline	24.2 ± 1.9	22.9 ± 2.4
3 Months (11-13 weeks)	23.1 ± 2.7	21.0 ± 0.6
15 Months (59-62 weeks)	26.4 ± 1.4	22.2 ± 1.4
24 Months (95-97 weeks)	25.2 ± 1.1	22.8 ± 2.8

Notes
[15] - At baseline n=7, T3 n=2, T15 n=2 and T24 n=2
[16] - At baseline n=10, T3 n=2, T15 n=3 and T24 n=3

BMI - 3 Month Treat Diff

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.067

Method

Mixed models analysis

Parameter type

3 Month Treatment Difference

Point estimate

-0.48

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

0.03

BMI - 15 Month Treat Diff

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.029

Method

Mixed models analysis

Parameter type

15 Month Treatment Difference

Point estimate

-0.73

Confidence interval

level

95%

sides

2-sided

lower limit

-1.39

upper limit

-0.08

BMI - Treatment Difference

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a continuous variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.02

Method

Mixed models analysis

Parameter type

Treatment Difference

Point estimate

-0.56

Confidence interval

level

95%

sides

2-sided

lower limit

-1.03

upper limit

-0.09

BMI - 24 Month Treat Diff

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.093

Method

Mixed models analysis

Parameter type

24 Month Treatment Difference

Point estimate

-0.92

Confidence interval

level

95%

sides

2-sided

lower limit

-2.01

upper limit

0.16

Secondary: Number of pulmonary exacerbations - median number of exacerbations during the 15 months following treatment commencement

Top of page

End point title

Number of pulmonary exacerbations - median number of exacerbations during the 15 months following treatment commencement

End point description

End point type

Secondary

End point timeframe

From baseline to 15 months.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	137	146
Units: Number of pulmonary exacerbations
median (inter-quartile range (Q1-Q3))	0 (0 to 1)	0 (0 to 1)

Mann–Whitney U test

Statistical analysis description

A Mann-Whitney U-test will test whether the distribution of number of exacerbations is the same in each treatment arm

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

283

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.09

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Number of pulmonary exacerbations - Number of participants experiencing at least one exacerbation during the first 15 months of follow up

Top of page

End point title

Number of pulmonary exacerbations - Number of participants experiencing at least one exacerbation during the first 15 months of follow up

End point description

End point type

Secondary

End point timeframe

From baseline to 15 months.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	137	146
Units: Subjects
0 exacerbations	99	94
>=1 exacerbations	38	52

Chi-squared test

Statistical analysis description

The number and percentage of patients experiencing at least one exacerbation in each treatment arm was reported. Treatment groups were compared using the chi-squared test.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

283

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.155

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

1.1

Secondary: Admission to hospital - Number of participants experiencing at least one hospital stay during the first 3 months of treatment

Top of page

End point title

Admission to hospital - Number of participants experiencing at least one hospital stay during the first 3 months of treatment

End point description

End point type

Secondary

End point timeframe

First 3 months of treatment.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	135	143
Units: Subjects
0 Hospital Stays	110	128
>=1 Hospital Stay	25	15

Admission to hospital - 3 months of treatment

Statistical analysis description

Number of participants experiencing at least one hospital stay during the first 3 months of treatment

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

278

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.057

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

1.77

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

3.2

Secondary: Admission to hospital - Number of participants experiencing at least one hospital stay during the 12 months following treatment

Top of page

End point title

Admission to hospital - Number of participants experiencing at least one hospital stay during the 12 months following treatment

End point description

End point type

Secondary

End point timeframe

12 months following treatment.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	129	136
Units: Subjects
0 Hospital Stays	89	75
>=1 Hospital Stay	40	61

Admission to hospital - 12 months

Statistical analysis description

Number of participants experiencing at least one hospital stay during the 12 months following treatment.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

265

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.02

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

0.69

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

0.95

Secondary: Admission to hospital - Number of participants experiencing at least one hospital stay between 15 and 24 months

Top of page

End point title

Admission to hospital - Number of participants experiencing at least one hospital stay between 15 and 24 months

End point description

Number of participants experiencing at least one hospital stay between 15 months and 24 months.

End point type

Secondary

End point timeframe

Between 15 months and 24 months.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	105	107
Units: Subjects
0 Hospital Stays	72	66
>=1 Hospital Stay	33	41

Admission to hospital - 15-24 months

Statistical analysis description

Number of participants experiencing at least one hospital stay between 15 months and 24 months

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

212

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.293

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

1.19

Secondary: Number of days spent as an inpatient in hospital - During treatment phase

Top of page

End point title

Number of days spent as an inpatient in hospital - During treatment phase

End point description

End point type

Secondary

End point timeframe

From baseline to 3 months.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	135	143
Units: Days
median (inter-quartile range (Q1-Q3))	0 (0 to 0)	0 (0 to 0)

Length of stay in days during the treatment phase

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

278

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.066

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Number of days spent as an inpatient in hospital - During the 12 months post treatment phase

Top of page

End point title

Number of days spent as an inpatient in hospital - During the 12 months post treatment phase

End point description

End point type

Secondary

End point timeframe

12 months post treatment.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	129	136
Units: days
median (inter-quartile range (Q1-Q3))	0 (0 to 3)	0 (0 to 13)

Length of stay during 12 months post treatment

Statistical analysis description

Length of stay in days during the 12 months post treatment phase.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

265

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.005

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Number of days spent as an inpatient in hospital - between 15 and 24 months follow up

Top of page

End point title

Number of days spent as an inpatient in hospital - between 15 and 24 months follow up

End point description

End point type

Secondary

End point timeframe

Between 15 and 24 months.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	99	102
Units: days
median (inter-quartile range (Q1-Q3))	0 (0 to 2.8)	0 (0 to 4)

Length of stay 15-24 months

Statistical analysis description

Length of stay in days, between 15 and 24 months follow up.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

201

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.261

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: CFQ - Physical functioning – Self Report

Top of page

End point title

CFQ - Physical functioning – Self Report

End point description

End point type

Secondary

End point timeframe

Basline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	53 ^[17]	61 ^[18]
Units: CFQ Score
arithmetic mean (standard deviation)
Baseline	80.70 ± 19.8	81 ± 17.4
3 months (11-13 weeks)	85.5 ± 15.1	78.1 ± 20
15 months (59-62 weeks)	83 ± 18	85.5 ± 14.7
24 months (95-97 weeks)	84.2 ± 14.6	86.2 ± 16.7

Notes
[17] - The number of patients at base line was 53, 49 at 3 months, 50 at 15 months and 44 at 24 months.
[18] - The number of patients at baseline was 61, 56 at 3 months, 50 at 15 months and 45 at 24 months

Physical functioning (Self-report) - 3 Month Diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups at T3 (derived from the model); and a p-value of the treatment effect.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.056

Method

Mixed models analysis

Parameter type

Mean difference at 3 months

Point estimate

6.63

Confidence interval

level

95%

sides

2-sided

lower limit

-0.18

upper limit

13.44

Physical functioning (Self-report) - 15 month diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups at T15 (derived from the model); and a p-value of the treatment effect.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.292

Method

Mixed models analysis

Parameter type

15 month treatment difference

Point estimate

-3.63

Confidence interval

level

95%

sides

2-sided

lower limit

-10.41

upper limit

3.16

Physical functioning (Self-report) - 24 Month diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups at T24 (derived from the model); and a p-value of the treatment effect.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.793

Method

Mixed models analysis

Parameter type

24 month treatment difference

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

-6.15

upper limit

8.03

Physical functioning (Self-report) - Treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a categorical variable . The following was reported: mean (SD) for each treatment group; mean (95% CI) and difference between treatment groups (derived from the model); and a p-value of the treatment effect.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.538

Method

Mixed models analysis

Parameter type

Treatment Difference

Point estimate

1.62

Confidence interval

level

95%

sides

2-sided

lower limit

-3.57

upper limit

6.8

Secondary: CFQ - Role/school functioning – Self Report

Top of page

End point title

CFQ - Role/school functioning – Self Report

End point description

End point type

Secondary

End point timeframe

baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	14 ^[19]	18 ^[20]
Units: CFQ Score
arithmetic mean (standard deviation)
Baseline	83.33 ± 19.06	91.20 ± 10.87
3 months (11-13 weeks)	87.82 ± 15.82	85.12 ± 21.73
15 months (59-62 weeks)	96.21 ± 8.63	88.33 ± 11.70
24 months (95-97 weeks)	94.44 ± 8.94	93.06 ± 9.29

Notes
[19] - At baseline n=14, at T3 n=13, at T15 n=11 and at T24 n=12
[20] - At baseline n=18, T3 n= 14, T15 n=15 and T24 n=12

Role/school functioning (Self-report)-3 Month diff

Statistical analysis description

A mixed-effects model for repeated measures will be fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.181

Method

Mixed models analysis

Parameter type

3 month treatment difference

Point estimate

8.92

Confidence interval

level

95%

sides

2-sided

lower limit

-4.42

upper limit

22.26

Role/school functioning (Self-report)15 treat diff

Statistical analysis description

A mixed-effects model for repeated measures will be fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.267

Method

Mixed models analysis

Parameter type

15 month treatment difference

Point estimate

7.66

Confidence interval

level

95%

sides

2-sided

lower limit

-6.21

upper limit

21.52

Role/school functioning (Self-report)24 month diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.328

Method

Mixed models analysis

Parameter type

24 month treatment difference

Point estimate

6.97

Confidence interval

level

95%

sides

2-sided

lower limit

-7.39

upper limit

21.33

Role/school functioning (Self-report) -treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a categorical variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.204

Method

Mixed models analysis

Parameter type

treatment difference

Point estimate

8.09

Confidence interval

level

95%

sides

2-sided

lower limit

-4.7

upper limit

20.89

Secondary: CFQ - Vitality – Self Report

Top of page

End point title

CFQ - Vitality – Self Report

End point description

End point type

Secondary

End point timeframe

Baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	14 ^[21]	18 ^[22]
Units: CFQ Score
arithmetic mean (standard deviation)
Baseline	50.60 ± 24.56	63.89 ± 20.21
3 Months (11-13 weeks)	68.59 ± 17.06	64.88 ± 21.48
15 Months (59-62 weeks)	74.24 ± 17.26	66.67 ± 18.90
24 Months (95-97 weeks)	72.92 ± 18.84	73.61 ± 16.60

Notes
[21] - At baseline n=14, T3 n=13, T15 n=11 and T24 n=12
[22] - At baseline n=18, T3 n=14, T15 n=15 and T24 n=12

Vitality (Self Report) - 3 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.182

Method

Mixed models analysis

Parameter type

3 Month Treatment Difference

Point estimate

9.07

Confidence interval

level

95%

sides

2-sided

lower limit

-4.56

upper limit

22.69

Vitality (Self Report) - 15 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.373

Method

Mixed models analysis

Parameter type

15 Month Treatment Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-6.88

upper limit

17.69

Vitality (Self Report) - 24 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.132

Method

Mixed models analysis

Parameter type

24 Month Treatment Difference

Point estimate

10.07

Confidence interval

level

95%

sides

2-sided

lower limit

-3.27

upper limit

23.41

Vitality (Self Report) - Treatment Difference

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a categorical variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.191

Method

Mixed models analysis

Parameter type

Treatment Difference

Point estimate

6.89

Confidence interval

level

95%

sides

2-sided

lower limit

-3.67

upper limit

17.45

Secondary: CFQ - Emotional functioning – Self Report

Top of page

End point title

CFQ - Emotional functioning – Self Report

End point description

End point type

Secondary

End point timeframe

Baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	53 ^[23]	61 ^[24]
Units: CFQ Score
arithmetic mean (standard deviation)
Baseline	78.8 ± 16.5	76.7 ± 14.5
3 Months (11-13 weeks)	78.1 ± 15.1	77.1 ± 14.8
15 Months (59-62 weeks)	80.8 ± 14.3	79 ± 13.6
24 Months (95-97 weeks)	80.3 ± 14.1	78.1 ± 13.5

Notes
[23] - At baseline n=53, T3 n=49, T15 n=50 and T24 n=44
[24] - At baseline n=56, T3 n=49, T15 n=50 and T24 n=45

Emotional functioning (Self-report) - 3 month diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.977

Method

Mixed models analysis

Parameter type

3 month treatment difference

Point estimate

-0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-5.06

upper limit

4.91

Emotional functioning (Self-report) -15 month diff

Statistical analysis description

A mixed-effects model for repeated measure was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.589

Method

Mixed models analysis

Parameter type

15 month treatment difference

Point estimate

-1.59

Confidence interval

level

95%

sides

2-sided

lower limit

-7.39

upper limit

4.22

Emotional functioning (Self-report) -24 month diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.964

Method

Mixed models analysis

Parameter type

24 month treatment difference

Point estimate

-0.14

Confidence interval

level

95%

sides

2-sided

lower limit

-6.19

upper limit

5.91

Emotional functioning (Self-report) - Treat Diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a categorical variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.807

Method

Mixed models analysis

Parameter type

treatment difference

Point estimate

-0.53

Confidence interval

level

95%

sides

2-sided

lower limit

-4.78

upper limit

3.73

Secondary: CFQ - Social functioning – Self Report

Top of page

End point title

CFQ - Social functioning – Self Report

End point description

End point type

Secondary

End point timeframe

baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	53 ^[25]	61 ^[26]
Units: CFQ Score
arithmetic mean (standard deviation)
Baseline	73 ± 17.6	73.7 ± 15.3
3 Months (11-13 weeks)	75.5 ± 16.5	72.2 ± 16.3
15 Months (59-62 weeks)	74.4 ± 18.1	73.8 ± 15.5
24 Weeks (95-97 weeks)	77.8 ± 13.9	73 ± 15.8

Notes
[25] - At baseline n=53, T3 n=49, T15 n=49 and T24 n=44
[26] - At baseline n=61, T3 n=56 , T15 n=50 and T24 n=45

Social functioning (Self-report) - 3 month diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.311

Method

Mixed models analysis

Parameter type

3 month treatment difference

Point estimate

2.98

Confidence interval

level

95%

sides

2-sided

lower limit

-2.82

upper limit

8.78

Social functioning (Self-report) - 15 month diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.498

Method

Mixed models analysis

Parameter type

15 month treatment difference

Point estimate

2.11

Confidence interval

level

95%

sides

2-sided

lower limit

-4.03

upper limit

8.25

Social functioning (Self-report) - 24 month diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.159

Method

Mixed models analysis

Parameter type

24 month treatment difference

Point estimate

4.31

Confidence interval

level

95%

sides

2-sided

lower limit

-1.72

upper limit

10.34

Social functioning (Self-report) - Treatment Diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a categorical variable. . The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.138

Method

Mixed models analysis

Parameter type

treatment difference

Point estimate

3.16

Confidence interval

level

95%

sides

2-sided

lower limit

-1.03

upper limit

7.36

Secondary: CFQ - Body Image – Self Report

Top of page

End point title

CFQ - Body Image – Self Report

End point description

End point type

Secondary

End point timeframe

Baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	52 ^[27]	61 ^[28]
Units: CFQ Score
arithmetic mean (standard deviation)
Baseline	90.4 ± 16.8	86.3 ± 17.6
3 Months (11-13 weeks)	90 ± 16.2	86.4 ± 16.4
15 Months (59-62 weeks)	88.2 ± 20	86.4 ± 17.7
24 Months (95-97 weeks)	90.4 ± 12	88.4 ± 18.3

Notes
[27] - At baseline n=52, T3 n= 49, T15 n=50 and T24 n=43
[28] - At baseline n=61, T3 n=56, T15 n=50 and T24 n=45

Body image (Self-report) - 3 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

113

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.443

Method

Mixed models analysis

Parameter type

3 month treatment difference

Point estimate

2.23

Confidence interval

level

95%

sides

2-sided

lower limit

-3.51

upper limit

7.97

Body image (Self-report) - 15 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

113

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.309

Method

Mixed models analysis

Parameter type

15 month treatment difference

Point estimate

-4.01

Confidence interval

level

95%

sides

2-sided

lower limit

-11.78

upper limit

3.77

Body image (Self-report) - 24 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

113

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.986

Method

Mixed models analysis

Parameter type

24 month treatment difference

Point estimate

-0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-7.58

upper limit

7.45

Body image (Self-report) - treatment difference

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a categorical variable.The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

113

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.931

Method

Mixed models analysis

Parameter type

treatment difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-4.43

upper limit

4.48

Secondary: CFQ - Eating Problems – Self Report

Top of page

End point title

CFQ - Eating Problems – Self Report

End point description

End point type

Secondary

End point timeframe

Baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	53 ^[29]	61 ^[30]
Units: CFQ Score
arithmetic mean (standard deviation)
Baseline	91 ± 16.5	84.9 ± 19.7
3 Months (11-13 weeks)	86.5 ± 18.8	82.1 ± 20.5
15 Months (59-62 weeks)	88.3 ± 17.4	86.4 ± 17.3
24 Months (95-97 weeks)	92.6 ± 13.6	87.4 ± 15.6

Notes
[29] - At baseline n=53, T3 n=49, T15 n=50 and T24 n=44
[30] - At baseline n=61, T3 n=56, T15 n=50 and T24 n=45

Eating problems (Self-report) - 3 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.453

Method

Mixed models analysis

Parameter type

3 month treatment difference

Point estimate

2.52

Confidence interval

level

95%

sides

2-sided

lower limit

-4.12

upper limit

9.16

Eating problems (Self-report) - 15 month treat dif

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.903

Method

Mixed models analysis

Parameter type

15 month treatment difference

Point estimate

-0.39

Confidence interval

level

95%

sides

2-sided

lower limit

-6.78

upper limit

Eating problems (Self-report) -24 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.31

Method

Mixed models analysis

Parameter type

24 month treatment difference

Point estimate

3.67

Confidence interval

level

95%

sides

2-sided

lower limit

-3.47

upper limit

10.81

Eating problems (Self-report) -treatment diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a categorical variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.506

Method

Mixed models analysis

Parameter type

treatment difference

Point estimate

1.66

Confidence interval

level

95%

sides

2-sided

lower limit

-3.27

upper limit

6.58

Secondary: CFQ - Treatment Burden – Self Report

Top of page

End point title

CFQ - Treatment Burden – Self Report

End point description

End point type

Secondary

End point timeframe

Baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	52 ^[31]	61 ^[32]
Units: CFQ Score
arithmetic mean (standard deviation)
Baseline	77.4 ± 21.7	74.1 ± 18.5
3 Months (11-13 weeks)	71.9 ± 25.4	70.7 ± 21.9
15 Months (59-62 weeks)	76.4 ± 18.7	71.1 ± 20.5
24 Months (95-97 weeks)	77.3 ± 20.3	74.8 ± 20.3

Notes
[31] - At baseline n=52, T3 n=49, T15 n=50 and T24 n=43
[32] - At baseline n=61, T3 n=56, T15 n=50 and T24 n=45

Treatment burden (Self-report) -3 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

113

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.244

Method

Mixed models analysis

Parameter type

3 month treatment difference

Point estimate

4.92

Confidence interval

level

95%

sides

2-sided

lower limit

-3.42

upper limit

13.27

Treatment burden (Self-report)-15 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

113

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.532

Method

Mixed models analysis

Parameter type

15 month treatment difference

Point estimate

2.86

Confidence interval

level

95%

sides

2-sided

lower limit

-6.19

upper limit

11.92

Treatment burden (Self-report)-24 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

113

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.343

Method

Mixed models analysis

Parameter type

24 month treatment difference

Point estimate

4.68

Confidence interval

level

95%

sides

2-sided

lower limit

-5.07

upper limit

14.43

Treatment burden (Self-report)- Treatment diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a categorical variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

113

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.167

Method

Mixed models analysis

Parameter type

treatment difference

Point estimate

4.23

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

10.27

Secondary: CFQ - Health Perceptions – Self Report

Top of page

End point title

CFQ - Health Perceptions – Self Report

End point description

End point type

Secondary

End point timeframe

Baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	14 ^[33]	18 ^[34]
Units: CFQ Score
arithmetic mean (standard deviation)
Baseline	65.87 ± 27.38	70.99 ± 16.23
3 Months (11-13 weeks)	78.21 ± 20.84	67.46 ± 27.38
15 Months (59-62 weeks)	80.81 ± 19.30	71.11 ± 25.13
24 Weeks (95-97 weeks)	72.22 ± 24.39	69.44 ± 20.17

Notes
[33] - At baseline n=14, T3 n=13, T15 n=11 and T24 n=12
[34] - At baseline n=18, T3 n=14, T15 n= 15 and T24 n=12

Health perceptions (Self-report)-3 month treat dif

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.045

Method

Mixed models analysis

Parameter type

3 month treatment difference

Point estimate

18.41

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

36.42

Health perceptions (Self-report)-15 month diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.583

Method

Mixed models analysis

Parameter type

15 month treatment difference

Point estimate

5.06

Confidence interval

level

95%

sides

2-sided

lower limit

-13.72

upper limit

23.84

Health perceptions (Self-report)-24 month diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.544

Method

Mixed models analysis

Parameter type

24 month treatment difference

Point estimate

6.33

Confidence interval

level

95%

sides

2-sided

lower limit

-14.89

upper limit

27.54

Health perceptions (Self-report)-treatment diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a categorical variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.13

Method

Mixed models analysis

Parameter type

treatment difference

Point estimate

12.46

Confidence interval

level

95%

sides

2-sided

lower limit

-3.96

upper limit

28.88

Secondary: CFQ - Weight – Self Report

Top of page

End point title

CFQ - Weight – Self Report

End point description

End point type

Secondary

End point timeframe

Baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	14 ^[35]	17 ^[36]
Units: CFQ Score
arithmetic mean (standard deviation)
Baseline	85.71 ± 25.2	78.43 ± 35.24
3 Months (11-13 weeks)	94.44 ± 19.25	92.86 ± 19.30
15 Months (59-62 weeks)	93.94 ± 13.48	84.44 ± 21.33
24 Months (95-97 weeks)	88.89 ± 25.95	80.56 ± 26.43

Notes
[35] - At baseline n=14, T3 n= 12, T15 n=11 and T24 n=12
[36] - At baseline n=17, T3 n=14 , T15 n=15, T24 n=12

Weight (self report) - 3 Month treatment diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Oral antibiotic therapy v Intravenous (IV) antibiotics

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.725

Method

Mixed models analysis

Parameter type

3 month treatment difference

Point estimate

2.51

Confidence interval

level

95%

sides

2-sided

lower limit

-12.06

upper limit

17.08

Weight (self report) - 15 Month treatment diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.888

Method

Mixed models analysis

Parameter type

15 month treatment difference

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-19.02

upper limit

21.83

Weight (self report) - 24 Month treatment diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.842

Method

Mixed models analysis

Parameter type

24 month treatment difference

Point estimate

2.68

Confidence interval

level

95%

sides

2-sided

lower limit

-24.8

upper limit

30.17

Weight (self report) - treatment difference

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a categorical variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.603

Method

Mixed models analysis

Parameter type

treatment difference

Point estimate

2.5

Confidence interval

level

95%

sides

2-sided

lower limit

-7.29

upper limit

12.29

Secondary: CFQ - Respiratory Symptoms – Self Report

Top of page

End point title

CFQ - Respiratory Symptoms – Self Report

End point description

End point type

Secondary

End point timeframe

Baseline to 24 Months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	53 ^[37]	61 ^[38]
Units: CFQ Score
arithmetic mean (standard deviation)
Baseline	67.0 ± 20.2	70.5 ± 18.5
3 Months (11-13 weeks)	76.8 ± 19.8	77 ± 15.9
15 Months (59-62 weeks)	80.4 ± 15.7	78.4 ± 16
24 Months (95-97 weeks)	83.2 ± 13.4	82.3 ± 13.4

Notes
[37] - At baseline n=53, T3 n=48, T15 n=49 and T24 n=44
[38] - At baseline n=61, at T3 n=48 , at T15 n=50 and T24 n=44

Resp Symp Self Report - 3 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.606

Method

Mixed models analysis

Parameter type

3 month treatment difference

Point estimate

1.79

Confidence interval

level

95%

sides

2-sided

lower limit

-5.06

upper limit

8.64

Resp Symp Self Report -15 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.374

Method

Mixed models analysis

Parameter type

15 month treatment difference

Point estimate

2.82

Confidence interval

level

95%

sides

2-sided

lower limit

-3.44

upper limit

9.08

Resp Symp Self Report -24 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.53

Method

Mixed models analysis

Parameter type

24 month treatment difference

Point estimate

2.08

Confidence interval

level

95%

sides

2-sided

lower limit

-4.47

upper limit

8.64

Resp Symp Self Report -treat diff

Statistical analysis description

A mixed-effects model for repeated measures wsa fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a categorical variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.344

Method

Mixed models analysis

Parameter type

treatment difference

Point estimate

2.27

Confidence interval

level

95%

sides

2-sided

lower limit

-2.47

upper limit

7.01

Secondary: CFQ - Digestive Symptoms – Self Report

Top of page

End point title

CFQ - Digestive Symptoms – Self Report

End point description

End point type

Secondary

End point timeframe

Baseline to 24 Months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	53 ^[39]	61 ^[40]
Units: CFQ Score
arithmetic mean (standard deviation)
Baseline	78.4 ± 25.3	74.5 ± 22.3
3 Months (11-13 weeks)	75.7 ± 29.1	74.2 ± 24.8
15 Months (59-62 weeks)	80.1 ± 24.1	80.2 ± 22.3
24 Months (95-97 weeks)	78.6 ± 23.3	83.2 ± 17.2

Notes
[39] - At baseline n=53, T3 n=47, T15 n=48 and T24 n=42
[40] - At baseline n=61, T3 n=56, T15 n=50 and T24 n=45

Digestive (Self report) - 3 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.551

Method

Mixed models analysis

Parameter type

3 month treatment difference

Point estimate

2.72

Confidence interval

level

95%

sides

2-sided

lower limit

-6.3

upper limit

11.75

Digestive (Self report) -15 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.998

Method

Mixed models analysis

Parameter type

15 month treatment difference

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-9.95

upper limit

9.93

Digestive (Self report) - treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a categorical variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.987

Method

Mixed models analysis

Parameter type

treatment difference

Point estimate

0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-6.23

upper limit

6.33

Digestive (Self report) - 24 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

114

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.581

Method

Mixed models analysis

Parameter type

24 month treatment difference

Point estimate

-2.49

Confidence interval

level

95%

sides

2-sided

lower limit

-11.44

upper limit

6.45

Secondary: CFQ - Physical functioning – Parent/Carer

Top of page

End point title

CFQ - Physical functioning – Parent/Carer

End point description

End point type

Secondary

End point timeframe

Baseline to 24 Months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	37 ^[41]	42 ^[42]
Units: CFQ Score
arithmetic mean (standard deviation)
Baseline	82.9 ± 18.3	85.9 ± 14.3
3 Months (11-13 weeks)	90.1 ± 10.5	84 ± 15.1
15 Months (59-62 weeks)	82.2 ± 20.9	86.8 ± 15.6
24 Months (95-97 weeks)	82.8 ± 22	89.2 ± 14.4

Notes
[41] - At baseline n=37, T3 n=38 , T15 n= 42, T24 n=32
[42] - At baseline n=42, T3 n=39, T15 n=32 and T24 n=33

Phys Fn - Parent/Carer - 3 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.033

Method

Mixed models analysis

Parameter type

3 month treat diff

Point estimate

6.18

Confidence interval

level

95%

sides

2-sided

lower limit

0.51

upper limit

11.85

Phys Fn - Parent/Carer - 15 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.223

Method

Mixed models analysis

Parameter type

15 month treat diff

Point estimate

-5.17

Confidence interval

level

95%

sides

2-sided

lower limit

-13.55

upper limit

3.22

Phys Fn - Parent/Carer - 24 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.342

Method

Mixed models analysis

Parameter type

24 month treat diff

Point estimate

-4.63

Confidence interval

level

95%

sides

2-sided

lower limit

-14.29

upper limit

5.03

Phys Fn - Parent/Carer - treatment difference

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a categorical variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.191

Method

Mixed models analysis

Parameter type

treat difference

Point estimate

3.62

Confidence interval

level

95%

sides

2-sided

lower limit

-1.85

upper limit

9.09

Secondary: CFQ - Role/school functioning – Parent/Carer

Top of page

End point title

CFQ - Role/school functioning – Parent/Carer

End point description

End point type

Secondary

End point timeframe

Baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	36 ^[43]	42 ^[44]
Units: CFQ Score
arithmetic mean (standard deviation)
Baseline	70.1 ± 27.1	66.3 ± 21.4
3 Months (11-13 weeks)	73 ± 25.1	66.7 ± 21
15 Months (59-62 weeks)	67.1 ± 29.3	69.8 ± 22.3
24 Months (95-97 weeks)	72.2 ± 25.9	78.1 ± 21.4

Notes
[43] - At baseline n= 36, T3 =37, T15 n=42 and T24 n=32
[44] - At baseline n=42, T3 n=39, T15 n=32 and T24 n=33

Role/School - P/C - 3 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.238

Method

Mixed models analysis

Parameter type

3 month treat diff

Point estimate

5.47

Confidence interval

level

95%

sides

2-sided

lower limit

-3.69

upper limit

14.64

Role/School - P/C - treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a categorical variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.845

Method

Mixed models analysis

Parameter type

treat diff

Point estimate

-0.67

Confidence interval

level

95%

sides

2-sided

lower limit

-7.49

upper limit

6.15

Role/School - P/C - 15 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.738

Method

Mixed models analysis

Parameter type

15 month treat diff

Point estimate

-1.47

Confidence interval

level

95%

sides

2-sided

lower limit

-10.22

upper limit

7.28

Role/School - P/C - 24 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.318

Method

Mixed models analysis

Parameter type

24 month treat diff

Point estimate

-5.06

Confidence interval

level

95%

sides

2-sided

lower limit

-15.09

upper limit

4.97

Secondary: CFQ - Vitality– Parent/Carer

Top of page

End point title

CFQ - Vitality– Parent/Carer

End point description

End point type

Secondary

End point timeframe

Baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	37 ^[45]	41 ^[46]
Units: CFQ Score
arithmetic mean (standard deviation)
Baseline	63.9 ± 17.4	67 ± 16.8
3 Months (11-13 weeks)	67.1 ± 13.8	62.2 ± 15.8
15 Months (59-62 weeks)	65.4 ± 18.1	66.7 ± 18.4
24 Months (95-97 weeks)	66.5 ± 17.1	68.3 ± 14.8

Notes
[45] - At baseline n=37, T3 n=38, T15 n=42 and T24 n=31
[46] - At baseline n=41, T3 n=39 , T15 n=32 and T24 n=33

Vitality - P/C - 3 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.059

Method

Mixed models analysis

Parameter type

3 month treat diff

Point estimate

6.53

Confidence interval

level

95%

sides

2-sided

lower limit

-0.26

upper limit

13.32

Vitality - P/C - 15 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.923

Method

Mixed models analysis

Parameter type

15 month treat diff

Point estimate

-0.44

Confidence interval

level

95%

sides

2-sided

lower limit

-9.36

upper limit

8.48

Vitality - P/C - treatment difference

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a categorical variable.The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.208

Method

Mixed models analysis

Parameter type

treat diff

Point estimate

3.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.11

upper limit

9.5

Vitality - P/C - 24 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.913

Method

Mixed models analysis

Parameter type

24 month treat diff

Point estimate

0.57

Confidence interval

level

95%

sides

2-sided

lower limit

-9.84

upper limit

10.98

Secondary: CFQ - Emotional functioning – Parent/Carer

Top of page

End point title

CFQ - Emotional functioning – Parent/Carer

End point description

End point type

Secondary

End point timeframe

Baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	36 ^[47]	42 ^[48]
Units: CFQ Score
arithmetic mean (standard deviation)
Baseline	77.2 ± 16.6	80.3 ± 17
3 Months (11-13 weeks)	80.7 ± 14.2	75.9 ± 18.1
15 Months (59-62 weeks)	79.9 ± 15.4	79.6 ± 15.8
24 Months (95-97 weeks)	83.1 ± 14.1	88.1 ± 10.5

Notes
[47] - At baseline n=36, T3 n=37, T15 n= 42, t24 n=32
[48] - At baseline n=42, T3 n=39, T15 n=32 adn T24 n=33

Emotional - P/C - 3 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.069

Method

Mixed models analysis

Parameter type

3 month treatment difference

Point estimate

5.97

Confidence interval

level

95%

sides

2-sided

lower limit

-0.47

upper limit

12.4

Emotional - P/C - 15 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.339

Method

Mixed models analysis

Parameter type

15 month treatment difference

Point estimate

3.32

Confidence interval

level

95%

sides

2-sided

lower limit

-3.56

upper limit

10.2

Emotional - P/C - treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a categorical variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.166

Method

Mixed models analysis

Parameter type

treatment difference

Point estimate

3.47

Confidence interval

level

95%

sides

2-sided

lower limit

-1.48

upper limit

8.41

Emotional - P/C - 24 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.668

Method

Mixed models analysis

Parameter type

24 month treatment difference

Point estimate

-1.69

Confidence interval

level

95%

sides

2-sided

lower limit

-9.55

upper limit

6.16

Secondary: CFQ - Body Image – Parent/Carer

Top of page

End point title

CFQ - Body Image – Parent/Carer

End point description

End point type

Secondary

End point timeframe

Baseline to 24 Months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	36 ^[49]	42 ^[50]
Units: CFQ Score
arithmetic mean (standard deviation)
Baseline	75.3 ± 21.4	72.5 ± 24.3
3 Months (11-13 weeks)	78.2 ± 22.5	72.9 ± 24.4
15 Months (59-62 weeks)	71.8 ± 28	76 ± 22.9
24 months (95-97 weeks)	71.9 ± 25.6	82.5 ± 23.7

Notes
[49] - At baseline n=36, T3 n=36 , T15 n=42 and T24 n=32
[50] - At baseline n=42, T3 n=39, T15 n=32, and T24 n=33

Body Image - P/C - 3 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Oral antibiotic therapy v Intravenous (IV) antibiotics

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.555

Method

Mixed models analysis

Parameter type

3 month treat diff

Point estimate

2.66

Confidence interval

level

95%

sides

2-sided

lower limit

-6.28

upper limit

11.59

Body Image - P/C - 15 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.922

Method

Mixed models analysis

Parameter type

15 month treat diff

Point estimate

-0.56

Confidence interval

level

95%

sides

2-sided

lower limit

-12.03

upper limit

10.9

Body Image - P/C - treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a categorical variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.644

Method

Mixed models analysis

Parameter type

treat diff

Point estimate

1.94

Confidence interval

level

95%

sides

2-sided

lower limit

-6.4

upper limit

10.28

Body Image - P/C - 24 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.679

Method

Mixed models analysis

Parameter type

24 month treat diff

Point estimate

2.58

Confidence interval

level

95%

sides

2-sided

lower limit

-9.81

upper limit

14.97

Secondary: CFQ - Eating Problems– Parent/Carer

Top of page

End point title

CFQ - Eating Problems– Parent/Carer

End point description

End point type

Secondary

End point timeframe

Baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	37 ^[51]	41 ^[52]
Units: CFQ Score
arithmetic mean (standard deviation)
Baseline	77 ± 29.7	78.9 ± 25.3
3 Months (11-13 weeks)	78.9 ± 26.7	72.6 ± 22.8
15 Months (59-62 weeks)	77.8 ± 27.9	78.6 ± 22.5
24 Months (95-97 weeks)	78.1 ± 24.1	82.3 ± 19.4

Notes
[51] - Baseline n=37, T3 n=34 , T15 n=39 and T24 n=32
[52] - At baseline n=41, T3 n=39, T15 n=32 and T24 n=32

Eating Problem P/C - 3 Month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.3

Method

Mixed models analysis

Parameter type

3 month treatment difference

Point estimate

4.6

Confidence interval

level

95%

sides

2-sided

lower limit

-4.19

upper limit

13.39

Eating Problem P/C - 15 Month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.174

Method

Mixed models analysis

Parameter type

15 month treatment difference

Point estimate

6.15

Confidence interval

level

95%

sides

2-sided

lower limit

-2.78

upper limit

15.08

Eating Problem P/C - 24 Month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.732

Method

Mixed models analysis

Parameter type

24 month treatment difference

Point estimate

-1.94

Confidence interval

level

95%

sides

2-sided

lower limit

-13.18

upper limit

9.31

Eating Problem P/C - Treatment Difference

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a categorical variable . The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.138

Method

Mixed models analysis

Parameter type

treatment difference

Point estimate

4.05

Confidence interval

level

95%

sides

2-sided

lower limit

-1.33

upper limit

9.44

Secondary: CFQ - Treatment Burden – Parent/Carer

Top of page

End point title

CFQ - Treatment Burden – Parent/Carer

End point description

End point type

Secondary

End point timeframe

Baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	37 ^[53]	42 ^[54]
Units: CFQ Score
arithmetic mean (standard deviation)
Baseline	57.8 ± 20.8	55.4 ± 23.4
3 Months (11-13 weeks)	59.3 ± 24.3	51.6 ± 23.8
15 Months (59-62 week)	57.7 ± 23.6	54.2 ± 20.9
24 Months (95-97 weeks)	58.3 ± 22.9	57.9 ± 21.8

Notes
[53] - At baseline n=37, T3 n=37, T15 n=42, T24 n=32
[54] - At baseline n=42, T3 n=39, T15 n=32, T24 n=33

Treatment Burden P/C - 3 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.718

Method

Mixed models analysis

Parameter type

3 month treat diff

Point estimate

1.99

Confidence interval

level

95%

sides

2-sided

lower limit

-8.94

upper limit

12.92

Treatment Burden P/C - 15 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.96

Method

Mixed models analysis

Parameter type

15 month treat diff

Point estimate

-0.28

Confidence interval

level

95%

sides

2-sided

lower limit

-11.25

upper limit

10.69

Treatment Burden P/C - 24 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.966

Method

Mixed models analysis

Parameter type

24 month treat diff

Point estimate

0.23

Confidence interval

level

95%

sides

2-sided

lower limit

-10.12

upper limit

10.57

Treatment Burden P/C - treatment difference

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a categorical variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.862

Method

Mixed models analysis

Parameter type

treatment difference

Point estimate

0.68

Confidence interval

level

95%

sides

2-sided

lower limit

-7.08

upper limit

8.44

Secondary: CFQ - Health Perceptions – Parent/Carer

Top of page

End point title

CFQ - Health Perceptions – Parent/Carer

End point description

End point type

Secondary

End point timeframe

Baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	36 ^[55]	42 ^[56]
Units: CFQ Score
arithmetic mean (standard deviation)
Baseline	71.6 ± 21	70.1 ± 18.3
3 Months (11-13 weeks)	69.9 ± 20	70.1 ± 18.4
15 Months (59-62 weeks)	67.9 ± 17.6	74.7 ± 15.5
24 Months (95-97 weeks)	72.2 ± 23.1	79.8 ± 17.7

Notes
[55] - At baseline n=36, T3 n=36, T15 n=42, T24 n=32
[56] - At bseline n=42, T3 n=39, T15 n=32, T24 n=33

Health Perceptions P/C - 3 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.988

Method

Mixed models analysis

Parameter type

3 month treat diff

Point estimate

-0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-9.37

upper limit

9.23

Health Perceptions P/C - 15 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.07

Method

Mixed models analysis

Parameter type

15 month treat diff

Point estimate

-7.25

Confidence interval

level

95%

sides

2-sided

lower limit

-15.09

upper limit

0.6

Health Perceptions P/C - 24 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.297

Method

Mixed models analysis

Parameter type

24 month treat diff

Point estimate

-6.76

Confidence interval

level

95%

sides

2-sided

lower limit

-19.6

upper limit

6.07

Health Perceptions P/C - treatment difference

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a categorical variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.115

Method

Mixed models analysis

Parameter type

treat diff

Point estimate

-4.39

Confidence interval

level

95%

sides

2-sided

lower limit

-9.88

upper limit

1.1

Secondary: CFQ - Weight – Parent/Carer

Top of page

End point title

CFQ - Weight – Parent/Carer

End point description

End point type

Secondary

End point timeframe

Baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	37 ^[57]	42 ^[58]
Units: CFQ Score
arithmetic mean (standard deviation)
Baseline	64 ± 31.8	69.8 ± 32.8
3 Months (11-13 weeks)	70.3 ± 33.1	62.2 ± 30.6
15 Months (59-62 weeks)	64.2 ± 35.3	69.8 ± 30.9
24 Months (95-97 weeks)	64.6 ± 35.9	69.7 ± 36.7

Notes
[57] - At baseline n=37, T3 n=37, T15 n=41 and T24 n=32
[58] - At baseline n=42, T3 n=37, T15 n=32 and T24 n=33

Weight - P/C - 3 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.294

Method

Mixed models analysis

Parameter type

3 month treat diff

Point estimate

7.66

Confidence interval

level

95%

sides

2-sided

lower limit

-6.78

upper limit

22.1

Weight - P/C - 15 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.886

Method

Mixed models analysis

Parameter type

15 month treat diff

Point estimate

-1.19

Confidence interval

level

95%

sides

2-sided

lower limit

-17.63

upper limit

15.26

Weight - P/C - 24 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.492

Method

Mixed models analysis

Parameter type

24 month treat diff

Point estimate

7.03

Confidence interval

level

95%

sides

2-sided

lower limit

-13.27

upper limit

27.33

Weight - P/C - treatment difference

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a categorical variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.247

Method

Mixed models analysis

Parameter type

treatment difference

Point estimate

6.37

Confidence interval

level

95%

sides

2-sided

lower limit

-4.5

upper limit

17.25

Secondary: CFQ - Respiratory Symptoms– Parent/Carer

Top of page

End point title

CFQ - Respiratory Symptoms– Parent/Carer

End point description

End point type

Secondary

End point timeframe

Baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	37 ^[59]	42 ^[60]
Units: CFQ Score
arithmetic mean (standard deviation)
Baseline	68.6 ± 20.9	73.5 ± 21.9
3 Months (11-13 weeks)	82.1 ± 18.1	79.1 ± 19.5
15 Months (59-62 weeks)	76.1 ± 18.2	82.6 ± 14.9
24 Months (95-97 weeks)	78.3 ± 20.2	82 ± 16.3

Notes
[59] - At baseline n=37, T3 n=37, T15 n=41 and T24 n=32
[60] - At baseline n=42, T3 n=39, T15 n=32 and T24 n=33

Resp Symp P/C - 3 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.39

Method

Mixed models analysis

Parameter type

3 month treat diff

Point estimate

4.11

Confidence interval

level

95%

sides

2-sided

lower limit

-5.36

upper limit

13.58

Resp Symp P/C - 15 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.432

Method

Mixed models analysis

Parameter type

15 month treat diff

Point estimate

-3.33

Confidence interval

level

95%

sides

2-sided

lower limit

-11.71

upper limit

5.06

Resp Symp P/C - 24 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.728

Method

Mixed models analysis

Parameter type

24 month treat diff

Point estimate

-2.11

Confidence interval

level

95%

sides

2-sided

lower limit

-14.15

upper limit

9.93

Resp Symp P/C - treament difference

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a categorical variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Oral antibiotic therapy v Intravenous (IV) antibiotics

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.885

Method

Mixed models analysis

Parameter type

treatment difference

Point estimate

-0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-7.01

upper limit

6.06

Secondary: CFQ - Digestive symptoms – Parent/Carer

Top of page

End point title

CFQ - Digestive symptoms – Parent/Carer

End point description

End point type

Secondary

End point timeframe

Baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	37 ^[61]	41 ^[62]
Units: CFQ Score
arithmetic mean (standard deviation)
Baseline	70.9 ± 22.6	74 ± 19.5
3 Months (11-13 weeks)	76.8 ± 20	74.5 ± 13.2
15 months (59-62 weeks)	77.2 ± 18.7	73.6 ± 20.5
24 Weeks (95-97 weeks)	76.4 ± 16.2	79.5 ± 17.4

Notes
[61] - At baseline n=37, T3 n=34 , T15 n=39 and T24 n=32
[62] - At baseline n=41, T3 n=39, T15 n=32 and T24 n=32

Digestive - P/C - 3 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.474

Method

Mixed models analysis

Parameter type

3 month treat diff

Point estimate

2.66

Confidence interval

level

95%

sides

2-sided

lower limit

-4.71

upper limit

10.03

Digestive - P/C - 15 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.405

Method

Mixed models analysis

Parameter type

15 month treat diff

Point estimate

3.54

Confidence interval

level

95%

sides

2-sided

lower limit

-4.9

upper limit

11.98

Digestive - P/C - 24 month treat diff

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group, time-point as a categorical variable and an interaction term (treatment group*time). The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.725

Method

Mixed models analysis

Parameter type

24 month treat diff

Point estimate

1.75

Confidence interval

level

95%

sides

2-sided

lower limit

-8.12

upper limit

11.62

Digestive - P/C - Treatment Difference

Statistical analysis description

A mixed-effects model for repeated measures was fitted, with an unstructured covariance matrix. The baseline measurement of the domain was fitted as a covariate along with treatment group and time-point as a categorical variable. The following was reported: mean (SD) for each treatment group; mean (95% CI) difference between treatment groups (derived from the model); and a p-value of the treatment effect

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.389

Method

Mixed models analysis

Parameter type

treatment difference

Point estimate

2.61

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

8.61

Secondary: Number of patients with at least one positive result of MRSA by 3 months

Top of page

End point title

Number of patients with at least one positive result of MRSA by 3 months

End point description

No analysis was possible due to there being 0 events in the IV group.

End point type

Secondary

End point timeframe

Baseline to three months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	136	145
Units: Subjects
0 Culture	136	144
>= 1 culture	0	1

No statistical analyses for this end point

Secondary: Number of patients with at least one positive result of Burkholderia cepacia complex (BC) by 3 months

Top of page

End point title

Number of patients with at least one positive result of Burkholderia cepacia complex (BC) by 3 months

End point description

No analysis was possible due to there being 0 events in the Oral group.

End point type

Secondary

End point timeframe

Baseline to three months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	136	144
Units: Subjects
0 culture	135	144
>=1 culture	1	0

No statistical analyses for this end point

Secondary: Number of patients with at least one positive result of Candida by 3 months

Top of page

End point title

Number of patients with at least one positive result of Candida by 3 months

End point description

End point type

Secondary

End point timeframe

Baseline to 3 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	137	146
Units: Subjects
0 culture	111	119
>=1 culture	26	27

Secondary Outcome - Relative Risk

Statistical analysis description

For each microorganism, the number and percentage with at least one positive result were presented split by treatment arm, and a relative risk and 95% confidence interval calculated. Chi-squared test (or if necessary Fisher’s exact test) was used to test for a difference between treatment groups.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

283

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.917

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

1.67

Secondary: Number of patients with at least one positive result of Aspergillus by 3 months

Top of page

End point title

Number of patients with at least one positive result of Aspergillus by 3 months

End point description

End point type

Secondary

End point timeframe

Baseline to 3 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	136	144
Units: Subjects
0 culture	130	139
>=1 culture	6	5

Secondary Outcome - Relative Risk

Statistical analysis description

For each microorganism, the number and percentage with at least one positive result waspresented split by treatment arm, and a relative risk and 95% confidence interval calculated. Chi-squared tests (or if necessary Fisher’s exact test) was used to test for differences between treatment groups.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

280

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.686

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

1.27

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

4.07

Secondary: Number of patients with at least one positive result of MRSA by 15 months

Top of page

End point title

Number of patients with at least one positive result of MRSA by 15 months

End point description

End point type

Secondary

End point timeframe

Baseline to 15 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	135	140
Units: Subjects
0 culture	131	138
>=1 culture	4	2

Secondary Outcome - Relative Risk

Statistical analysis description

For each microorganism, the number and percentage with at least one positive result was presented split by treatment arm, and a relative risk and 95% confidence interval calculated. Chi-squared tests (or if necessary Fisher’s exact test) was used to test for differences between treatment groups.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

275

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.441

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

2.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.39

upper limit

11.14

Secondary: Number of patients with at least one positive result of Burkholderia cepacia complex (BC) by 15 months

Top of page

End point title

Number of patients with at least one positive result of Burkholderia cepacia complex (BC) by 15 months

End point description

End point type

Secondary

End point timeframe

Baseline to 15 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	135	139
Units: Subjects
0 culture	133	135
>= 1 culture	2	4

Secondary Outcome - Relative Risk

Statistical analysis description

For each microorganism, the number and percentage with at least one positive result was presented split by treatment arm, and a relative risk and 95% confidence interval calculated. Chi-squared tests (or if necessary Fisher’s exact test) was used to test for differences between treatment groups.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

274

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.684

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

0.51

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

2.76

Secondary: Number of patients with at least one positive result of Candida by 15 months

Top of page

End point title

Number of patients with at least one positive result of Candida by 15 months

End point description

End point type

Secondary

End point timeframe

Baseline to 15 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	136	142
Units: Subjects
0 culture	81	87
>=1 cultures	55	55

Secondary Outcome - Relative Risk

Statistical analysis description

For each microorganism, the number and percentage with at least one positive result was presented split by treatment arm, and a relative risk and 95% confidence interval calculated. Chi-squared test (or if necessary Fisher’s exact test) was used to test for a difference between treatment groups.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

278

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.771

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.4

Secondary: Number of patients with at least one positive result of Aspergillus by 15 months

Top of page

End point title

Number of patients with at least one positive result of Aspergillus by 15 months

End point description

End point type

Secondary

End point timeframe

baseline to 15 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	135	139
Units: Subjects
0 culture	121	119
>=1 cultures	14	20

Secondary Outcome - Relative Risk

Statistical analysis description

For each microorganism, the number and percentage with at least one positive result will be presented split by treatment arm, and a relative risk and 95% confidence interval calculated. Chi-squared test (or if necessary Fisher’s exact test) will be used to test for a difference between treatment groups.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

274

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.313

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

0.72

Confidence interval

level

95%

sides

2-sided

lower limit

0.38

upper limit

1.37

Secondary: Number of patients with at least one positive result of MRSA by 24 months

Top of page

End point title

Number of patients with at least one positive result of MRSA by 24 months

End point description

End point type

Secondary

End point timeframe

Baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	132	133
Units: Subjects
0 culture	130	129
>=1 cultures	2	4

Secondary Outcome - Relative Risk

Statistical analysis description

For each microorganism, the number and percentage with at least one positive result was presented split by treatment arm, and a relative risk and 95% confidence interval calculated. Chi-squared test (or if necessary Fisher’s exact test) was used to test for a difference between treatment groups.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

265

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.684

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.09

upper limit

2.7

Secondary: Number of patients with at least one positive result of Burkholderia cepacia complex (BC) by 24 months

Top of page

End point title

Number of patients with at least one positive result of Burkholderia cepacia complex (BC) by 24 months

End point description

End point type

Secondary

End point timeframe

Baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	132	133
Units: Subjects
0 culture	130	129
>=1 cultures	2	4

Secondary Outcome - Relative Risk

Statistical analysis description

For each microorganism, the number and percentage with at least one positive result was presented split by treatment arm, and a relative risk and 95% confidence interval calculated. Chi-squared test (or if necessary Fisher’s exact test) was used to test for a difference between treatment groups.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

265

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.684

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.09

upper limit

2.7

Secondary: Number of patients with at least one positive result of Candida by 24 months

Top of page

End point title

Number of patients with at least one positive result of Candida by 24 months

End point description

End point type

Secondary

End point timeframe

Baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	135	137
Units: Subjects
0 culture	76	81
>=1 culture	59	56

Secondary Outcome - Relative Risk

Statistical analysis description

For each microorganism, the number and percentage with at least one positive result was presented split by treatment arm, and a relative risk and 95% confidence interval calculated. Chi-squared test (or if necessary Fisher’s exact test) was used to test for a difference between treatment groups.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

272

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.637

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

1.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.41

Secondary: Number of patients with at least one positive result of Aspergillus by 24 months

Top of page

End point title

Number of patients with at least one positive result of Aspergillus by 24 months

End point description

End point type

Secondary

End point timeframe

Baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	134	134
Units: Subjects
0 culture	114	111
>=1 cultures	20	23

Secondary Outcome - Relative Risk

Statistical analysis description

For each microorganism, the number and percentage with at least one positive result was presented split by treatment arm, and a relative risk and 95% confidence interval calculated. Chi-squared test (or if necessary Fisher’s exact test) was used to test for a difference between treatment groups.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.618

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

1.51

Secondary: Carer Burden - Median number of days absence during the 15 months following randomisation

Top of page

End point title

Carer Burden - Median number of days absence during the 15 months following randomisation

End point description

End point type

Secondary

End point timeframe

Randomisation until 15 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	131	139
Units: Days
median (inter-quartile range (Q1-Q3))	0 (0 to 1)	0 (0 to 1)

Secondary Outcome - Median

Statistical analysis description

The number of days spent absent from work or education was presented as a median with 95% confidence interval for each treatment arm, together with the interquartile range, min and max. A Mann Whitney test was used to detect differences in the distributions of carer burden between the two treatment groups

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

270

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.616 ^[63]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[63] - The median and 95% Confidence Interval for each group was 0 (0,0). The minimum and maximum for the IV and oral group resepectively were 0 and 24 and 0 and 98.

Secondary: Carer Burden - Number of carers experiencing at least one episode of absence during the first 15 months of follow up

Top of page

End point title

Carer Burden - Number of carers experiencing at least one episode of absence during the first 15 months of follow up

End point description

End point type

Secondary

End point timeframe

Baseline to 15 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	131	139
Units: Subjects
0 absence	87	90
>=1 absence	44	49

Secondary Outcome - Relative Risk

Statistical analysis description

Whether carers have been absent from education or work or not during the first 15 months post randomisation, was analysed using a relative risk, presented with a 95% confidence interval and a chi squared test.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

270

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.774

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

1.22

Secondary: Participant burden - Median number of days absence during the 15 months following treatment randomisation

Top of page

End point title

Participant burden - Median number of days absence during the 15 months following treatment randomisation

End point description

End point type

Secondary

End point timeframe

Baseline to 15 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	131	140
Units: days
median (inter-quartile range (Q1-Q3))	0 (0 to 6.2)	0 (0 to 10)

Secondary Outcome - Median

Statistical analysis description

The number of days spent absent from work or education will be presented as a median with 95% confidence interval for each treatment arm, together with the interquartile range, min and max. A Mann Whitney test was used to detect differences in the distributions of carer burden between the two treatment groups

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

271

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.263 ^[64]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[64] - The median and 95% CI for the IV group was 0 (0,2) and for the oral group was 1 (0,3). The minimum and maximum for the IV group was 0 and 56 and was 0 and 113 for the oral group.

Secondary: Participant burden - Number of participants experiencing at least one episode of absence during the first 15 months of follow up

Top of page

End point title

Participant burden - Number of participants experiencing at least one episode of absence during the first 15 months of follow up

End point description

End point type

Secondary

End point timeframe

baseline to 15 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	131	140
Units: Subjects
0 absence	66	64
>=1 absence	65	76

Secondary Outcome - Relative Risk

Statistical analysis description

Whether participants have been absent from education or work or not during the first 15 months post randomisation, was analysed using a relative risk, presented with a 95% confidence interval and a chi squared test.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

271

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.442

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

1.41

Secondary: Number of days spent as an inpatient in hospital during treatment phase - Sensitivity Analysis 1

Top of page

End point title

Number of days spent as an inpatient in hospital during treatment phase - Sensitivity Analysis 1

End point description

End point type

Secondary

End point timeframe

treatment phase

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	135	143
Units: days
median (inter-quartile range (Q1-Q3))	0 (0 to 0)	0 (0 to 0)

Sens 1 - Length of stay - tmt phase

Statistical analysis description

The number of patients with hospital stays and their median, interquartile range and minimum and maximum total length of stay was calculated for each treatment arm and each time-period. A Mann-Whitney test was be used to detect differences between treatment groups for each time-period of interest.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

278

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.05

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Number of days spent as an inpatient in hospital during 12 months post treatment- Sensitivity Analysis 1

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End point title

Number of days spent as an inpatient in hospital during 12 months post treatment- Sensitivity Analysis 1

End point description

End point type

Secondary

End point timeframe

12 month post treatment phase

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	129	136
Units: days
median (inter-quartile range (Q1-Q3))	0 (0 to 2)	0 (0 to 12.5)

Sens 1 - Length of stay - 12 months post treat

Statistical analysis description

The number of patients with hospital stays and their median, interquartile range and minimum and maximum total length of stay was calculated for each treatment arm and each time-period. A Mann-Whitney test was used to detect differences between treatment groups for each time-period of interest.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

265

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.007

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Number of days spent as an inpatient in hospital between 15 and 24 months - Sensitivity Analysis 1

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End point title

Number of days spent as an inpatient in hospital between 15 and 24 months - Sensitivity Analysis 1

End point description

End point type

Secondary

End point timeframe

between 15 and 24 months follow up

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	99	101
Units: days
median (inter-quartile range (Q1-Q3))	0 (0 to 1)	0 (0 to 3)

Sens 1 - Length of stay - 15-24mths

Statistical analysis description

The number of patients with hospital stays and their median, interquartile range and minimum and maximum total length of stay was calculated for each treatment arm and each time-period. A Mann-Whitney test was used to detect differences between treatment groups for each time-period of interest.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.273

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Number of days spent as an inpatient in hospital during treatment phase - Sensitivity Analysis 2

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End point title

Number of days spent as an inpatient in hospital during treatment phase - Sensitivity Analysis 2

End point description

End point type

Secondary

End point timeframe

treatment phase

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	135	143
Units: days
median (inter-quartile range (Q1-Q3))	0 (0 to 0)	0 (0 to 0)

Sens 2 - length of stay - tmt phase

Statistical analysis description

The number of patients with hospital stays and their median, interquartile range and minimum and maximum total length of stay was calculated for each treatment arm and each time-period. A Mann-Whitney test was used to detect differences between treatment groups for each time-period of interest.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

278

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Number of days spent as an inpatient in hospital during 12 months post treatment- Sensitivity Analysis 2

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End point title

Number of days spent as an inpatient in hospital during 12 months post treatment- Sensitivity Analysis 2

End point description

End point type

Secondary

End point timeframe

12 months post treatment phase

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	129	136
Units: days
median (inter-quartile range (Q1-Q3))	0 (0 to 1)	0 (0 to 13)

Sens 2 - length of stay - 12 months post

Statistical analysis description

The number of patients with hospital stays and their median, interquartile range and minimum and maximum total length of stay was calculated for each treatment arm and each time-period. A Mann-Whitney test was used to detect differences between treatment groups for each time-period of interest.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

265

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Number of days spent as an inpatient between 15 and 24 months- Sensitivity Analysis 2

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End point title

Number of days spent as an inpatient between 15 and 24 months- Sensitivity Analysis 2

End point description

End point type

Secondary

End point timeframe

between 15 and 24 months follow up

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	99	102
Units: days
median (inter-quartile range (Q1-Q3))	0 (0 to 1)	0 (0 to 3)

Sens 2 - Length of Stay - 15-24 months

Statistical analysis description

The number of patients with hospital stays and their median, interquartile range and minimum and maximum total length of stay was calculated for each treatment arm and each time-period. A Mann-Whitney test was used to detect differences between treatment groups for each time-period of interest.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

201

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.574

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Number of patients with at least one positive result of another organism during the study

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End point title

Number of patients with at least one positive result of another organism during the study

End point description

End point type

Secondary

End point timeframe

Baseline to 24 months

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	137	148
Units: Subjects
Aeromonas	3	1
Acinetobacter	15	7
Achromobacter	2	4
Chryseobacterium	2	2
Coliform (genera other than those listed separatel	9	10
Elizabethkingia	0	2
Enterobacter	10	7
Escherichia (specifically E. coli)	6	5
Haemophilus	44	39
Klebsiella	7	11
Moraxella	9	5
Mycobacterium	1	3
Ochrobactrum	2	0
Pantoea	2	0
Pseudomonas (species other than P. aeruginosa)	10	10
Serratia	5	3
Staphylococcus	60	63
Stenotrophomonas	7	10
Streptococcus	15	20
Unspecified/unidentified/commencals	11	7
Other	9	2
Fusarium	1	0
Rhodotorula	0	1
Scedosporium	0	2
Yeasts (other than Candida)	19	13
Adenovirus	1	2
Enterovirus	3	3
Influenza viruses	3	3
Metapneumovirus	2	0

No statistical analyses for this end point

Other pre-specified: Primary efficacy assessment – Sensitivity analysis 1: All patients followed up past 3 months but with no 15 month sample classified as successes

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End point title

Primary efficacy assessment – Sensitivity analysis 1: All patients followed up past 3 months but with no 15 month sample classified as successes

End point description

End point type

Other pre-specified

End point timeframe

3 months after the start of treatment to 15 months after the start of treatment.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	136	144
Units: Subjects
Successful eradication	66	82
Unsuccessful eradication	70	62

Sensitivity analysis 1

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

280

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.159

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

1.07

Other pre-specified: Primary efficacy assessment – Sensitivity analysis 2 – All patients followed up past 3 months but with no 15-month sample classified as failures

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End point title

Primary efficacy assessment – Sensitivity analysis 2 – All patients followed up past 3 months but with no 15-month sample classified as failures

End point description

End point type

Other pre-specified

End point timeframe

From 3 months after the start of treatment to 15 months after the start of treatment.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	136	144
Units: Subjects
Successful eradication	55	68
Unsuccessful eradication	81	76

Sensitivity analysis 2

Statistical analysis description

Primary efficacy assessment – Sensitivity analysis 2: All patients followed up past 3 months but with no 15-month sample classified as failures.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

280

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.253

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

1.12

Other pre-specified: Sensitivity analysis 3 – All patients followed up for more than 15 months but with no 15-month sample classified as success/failure in accordance with the next sample taken after the 15-month window

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End point title

Sensitivity analysis 3 – All patients followed up for more than 15 months but with no 15-month sample classified as success/failure in accordance with the next sample taken after the 15-month window

End point description

End point type

Other pre-specified

End point timeframe

From 3 months after the start of treatment to 15 months after the start of treatment.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	136	144
Units: Subjects
Successful eradication	66	81
Unsuccessful eradication	70	63

Sensitivity analysis 3

Statistical analysis description

Primary efficacy assessment – Sensitivity analysis 3: All patients followed up for more than 15 months but with no 15-month sample classified as success/failure in accordance with the next sample taken after the 15-month window.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

280

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.196

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

1.08

Other pre-specified: Primary efficacy assessment – Sensitivity analysis 4: Centre effect

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End point title

Primary efficacy assessment – Sensitivity analysis 4: Centre effect

End point description

The model with site as a random effect was not statistically different to the model without a random effect.

End point type

Other pre-specified

End point timeframe

From 3 months after the start of treatment to 15 months after the start of treatment.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	125	130
Units: Subjects	55	68

No statistical analyses for this end point

Other pre-specified: Primary efficacy assessment – Sensitivity analysis 5: T3 and T15 extended to +10 weeks (Post hoc) - successful eradication

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End point title

Primary efficacy assessment – Sensitivity analysis 5: T3 and T15 extended to +10 weeks (Post hoc) - successful eradication

End point description

End point type

Other pre-specified

End point timeframe

From 3 months after the start of treatment to 15 months after the start of treatment.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	132	139
Units: Subjects
Successful eradication	61	73
Unsuccessful eradication	71	66

Sensitivity analysis 5 - Successful eradication

Statistical analysis description

Sensitivity analysis 5: T3 and T15 extended to +10 weeks (Post hoc)

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

271

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.299

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

1.12

Other pre-specified: Primary efficacy assessment – Sensitivity analysis 5: T3 and T15 extended to +10 weeks (Post hoc) - unsuccessful eradication

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End point title

Primary efficacy assessment – Sensitivity analysis 5: T3 and T15 extended to +10 weeks (Post hoc) - unsuccessful eradication

End point description

End point type

Other pre-specified

End point timeframe

Number of participants who had unsuccessful eradication at their three-month visit (T3 extended to +10 weeks (Post hoc)).

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	124	135
Units: Subjects
Successful eradication	102	123
Unsuccessful eradication	22	12

Sensitivity analysis 5 - Unsuccessful eradication

Statistical analysis description

Number of participants who had unsuccessful eradication at their three-month visit (T3 extended to +10 weeks (Post hoc)).

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

259

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.035

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

1.03

upper limit

3.86

Other pre-specified: Sensitivity analysis: Time to reoccurrence of original P.aeruginosa infection (Those with reoccurrence but unknown strain assumed to be same as baseline and T0 adjusted to be date of treatment commencement rather than date of randomisation)

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End point title

Sensitivity analysis: Time to reoccurrence of original P.aeruginosa infection (Those with reoccurrence but unknown strain assumed to be same as baseline and T0 adjusted to be date of treatment commencement rather than date of randomisation)

End point description

End point type

Other pre-specified

End point timeframe

From baseline to 24 months.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	137	148
Units: Subjects
Reoccurrence of original P.aeruginosa infection	74	66
Censored	63	82

Sensitivity analysis

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

285

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.06

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.38

Confidence interval

level

95%

sides

2-sided

lower limit

0.99

upper limit

1.92

Other pre-specified: Sensitivity analysis: Time to reoccurrence of original P.aeruginosa infection (Those with reoccurrence but unknown strain assumed to be different to baseline and T0 adjusted to be date of treatment commencement rather than date of randomisation)

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End point title

Sensitivity analysis: Time to reoccurrence of original P.aeruginosa infection (Those with reoccurrence but unknown strain assumed to be different to baseline and T0 adjusted to be date of treatment commencement rather than date of randomisation)

End point description

End point type

Other pre-specified

End point timeframe

From baseline to 24 months.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	137	148
Units: Subjects
Reoccurence of original P.aeruginosa infection	21	14
Censored	116	134

Sensitivity analysis

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

285

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.074

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.94

upper limit

3.64

Other pre-specified: Additional analysis 1: Time to first pulmonary exacerbation

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End point title

Additional analysis 1: Time to first pulmonary exacerbation

End point description

End point type

Other pre-specified

End point timeframe

From baseline to 24 months.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	137	148
Units: Subjects
Number of patients who had pulmonary exacerbation	48	63
Censored	89	85

Time to first pulmonary exacerbation

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

285

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.73

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

1.06

Other pre-specified: Additional analysis 2: At least one exacerbation during the treatment phase

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End point title

Additional analysis 2: At least one exacerbation during the treatment phase

End point description

End point type

Other pre-specified

End point timeframe

Treatment phase.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	135	144
Units: Subjects
0 exacerbations	127	129
>=1 exacerbations	8	15

1+ exacerbations during the treatment phase

Statistical analysis description

The number and percentage of patients experiencing at least one exacerbation in each treatment arm was reported. Treatment groups were compared using the chi-squared test.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

279

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.173

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

0.57

Confidence interval

level

95%

sides

2-sided

lower limit

0.25

upper limit

1.3

Other pre-specified: Additional analysis 2: At least one exacerbation during the first year following treatment

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End point title

Additional analysis 2: At least one exacerbation during the first year following treatment

End point description

End point type

Other pre-specified

End point timeframe

From 3 months to 15 months.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	131	136
Units: Subjects
0 exacerbations	100	90
>=1 exacerbations	31	46

1+ exacerbations between 3-15 months

Statistical analysis description

The number and percentage of patients experiencing at least one exacerbation in each treatment arm was reported. Treatment groups were compared using the chi-squared test.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

267

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.067

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.48

upper limit

1.03

Other pre-specified: Additional analysis 2: At least one exacerbation during the second year following treatment

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End point title

Additional analysis 2: At least one exacerbation during the second year following treatment

End point description

End point type

Other pre-specified

End point timeframe

From 15 months to 24 months.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	99	103
Units: Subjects
0 exacerbations	85	77
>=1 exacerbations	14	26

1+ exacerbations between 15-24 months

Statistical analysis description

The number and percentage of patients experiencing at least one exacerbation in each treatment arm was reported. Treatment groups were compared using the chi-squared test.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.048

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

0.56

Confidence interval

level

95%

sides

2-sided

lower limit

0.31

upper limit

1.01

Other pre-specified: Sensitivity analysis - Admission to hospital - Number of participants experiencing at least one hospital stay during the first 3 months of treatment

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End point title

Sensitivity analysis - Admission to hospital - Number of participants experiencing at least one hospital stay during the first 3 months of treatment

End point description

End point type

Other pre-specified

End point timeframe

First 3 months of treatment.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	135	143
Units: Subjects
0 Hospital Stays	111	134
>=1 Hospital Stay	24	9

Admission to hospital - 3 months of treatment

Statistical analysis description

The secondary outcome analysis was ran under the assumption that where there is uncertainty about which period hospital stay occurred in, all reported hospital stay occurs in the time-period least likely.

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

278

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

2.82

Confidence interval

level

95%

sides

2-sided

lower limit

1.36

upper limit

5.86

Other pre-specified: Sensitivity analysis - Number of participants experiencing at least one hospital stay during the 12 months following treatment

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End point title

Sensitivity analysis - Number of participants experiencing at least one hospital stay during the 12 months following treatment

End point description

End point type

Other pre-specified

End point timeframe

12 months following treatment.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	129	136
Units: Subjects
0 Hospital Stays	90	73
>=1 Hospital Stay	39	63

Admission to hospital - 12 months

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

265

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.007

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

0.65

Confidence interval

level

95%

sides

2-sided

lower limit

0.47

upper limit

0.9

Other pre-specified: Sensitivity analysis - Admission to hospital - Number of participants experiencing at least one hospital stay between 15 months and 24 months

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End point title

Sensitivity analysis - Admission to hospital - Number of participants experiencing at least one hospital stay between 15 months and 24 months

End point description

End point type

Other pre-specified

End point timeframe

Between 15 and 24 months.

End point values	Intravenous (IV) antibiotics	Oral antibiotic therapy
Number of subjects analysed	104	108
Units: Subjects
0 Hospital Stays	70	67
>=1 Hospital Stay	34	41

Admission to hospital - 15-24 months

Statistical analysis description

Comparison groups

Intravenous (IV) antibiotics v Oral antibiotic therapy

Number of subjects included in analysis

212

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.422

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

1.24

Adverse events

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Timeframe for reporting adverse events

Only AEs occuring from commencement of allocated treatment until 28 days after cessation of allocated treatment were reported during the trial.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

Intravenous (IV) antibiotics

Reporting group description

Reporting group title

Oral antibiotic therapy

Reporting group description

Serious adverse events	Intravenous (IV) antibiotics	Oral antibiotic therapy
Total subjects affected by serious adverse events
subjects affected / exposed	10 / 126 (7.94%)	14 / 146 (9.59%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0
Vascular disorders
Thrombophlebitis
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Surgical and medical procedures
Catheter management
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Headache
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
General physical health deterioration
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Distal intestinal obstruction syndrome
subjects affected / exposed	2 / 126 (1.59%)	1 / 146 (0.68%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Hepatic failure
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Productive cough
subjects affected / exposed	0 / 126 (0.00%)	3 / 146 (2.05%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Lung consolidation
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Rash pruritic
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Anxiety
Additional description: Event was that after 5 weeks on trial developed voices in his head and obsessive behaviours and anxiety at night.
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Haematuria
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Bronchiolitis
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Croup infectious
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infective pulmonary exacerbation of cystic fibrosis
subjects affected / exposed	1 / 126 (0.79%)	1 / 146 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pseudomonas infection
subjects affected / exposed	0 / 126 (0.00%)	3 / 146 (2.05%)
occurrences causally related to treatment / all	0 / 0	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Rhinitis
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Intravenous (IV) antibiotics	Oral antibiotic therapy
Total subjects affected by non serious adverse events
subjects affected / exposed	64 / 126 (50.79%)	75 / 146 (51.37%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
General disorders and administration site conditions
Administration site bruise
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Administration site pain
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Adverse drug reaction
subjects affected / exposed	1 / 126 (0.79%)	1 / 146 (0.68%)
occurrences all number	1	1
Catheter site related reaction
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Chest pain
subjects affected / exposed	1 / 126 (0.79%)	1 / 146 (0.68%)
occurrences all number	1	1
Influenza like illness
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Malaise
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Pain
subjects affected / exposed	1 / 126 (0.79%)	1 / 146 (0.68%)
occurrences all number	1	1
Pyrexia
subjects affected / exposed	2 / 126 (1.59%)	7 / 146 (4.79%)
occurrences all number	2	7
Swelling
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Immune system disorders
Seasonal allergy
subjects affected / exposed	1 / 126 (0.79%)	1 / 146 (0.68%)
occurrences all number	1	1
Respiratory, thoracic and mediastinal disorders
Bronchospasm
subjects affected / exposed	1 / 126 (0.79%)	1 / 146 (0.68%)
occurrences all number	1	1
Cough
subjects affected / exposed	22 / 126 (17.46%)	23 / 146 (15.75%)
occurrences all number	26	28
Epistaxis
subjects affected / exposed	1 / 126 (0.79%)	2 / 146 (1.37%)
occurrences all number	1	2
Haemoptysis
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Nasal congestion
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Pharyngeal oedema
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Productive cough
subjects affected / exposed	5 / 126 (3.97%)	8 / 146 (5.48%)
occurrences all number	5	8
Sputum increased
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Wheezing
subjects affected / exposed	3 / 126 (2.38%)	6 / 146 (4.11%)
occurrences all number	3	6
Psychiatric disorders
Enuresis
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Product issues
Device occlusion
subjects affected / exposed	2 / 126 (1.59%)	0 / 146 (0.00%)
occurrences all number	2	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Blood glucose increased
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Chest X-ray abnormal
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Enterobacter test positive
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Haemophilus test positive
subjects affected / exposed	2 / 126 (1.59%)	0 / 146 (0.00%)
occurrences all number	2	0
Klebsiella test positive
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Pseudomonas test
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Pseudomonas test positive
subjects affected / exposed	1 / 126 (0.79%)	2 / 146 (1.37%)
occurrences all number	1	2
Pulmonary function test
subjects affected / exposed	0 / 126 (0.00%)	2 / 146 (1.37%)
occurrences all number	0	2
Pulmonary function test decreased
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Stenotrophomonas test positive
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Streptococcus test positive
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	1 / 126 (0.79%)	2 / 146 (1.37%)
occurrences all number	1	2
Skull fracture
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Sunburn
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Wrist fracture
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Nervous system disorders
Dizziness
subjects affected / exposed	1 / 126 (0.79%)	1 / 146 (0.68%)
occurrences all number	1	1
Febrile convulsion
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Headache
subjects affected / exposed	2 / 126 (1.59%)	0 / 146 (0.00%)
occurrences all number	3	0
Lethargy
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Migraine
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Ear and labyrinth disorders
Ear discomfort
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Ear pain
subjects affected / exposed	0 / 126 (0.00%)	2 / 146 (1.37%)
occurrences all number	0	2
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 126 (0.79%)	2 / 146 (1.37%)
occurrences all number	1	2
Abdominal pain upper
subjects affected / exposed	1 / 126 (0.79%)	1 / 146 (0.68%)
occurrences all number	1	1
Constipation
subjects affected / exposed	1 / 126 (0.79%)	1 / 146 (0.68%)
occurrences all number	1	1
Diarrhoea
subjects affected / exposed	5 / 126 (3.97%)	3 / 146 (2.05%)
occurrences all number	6	3
Distal intestinal obstruction syndrome
subjects affected / exposed	2 / 126 (1.59%)	3 / 146 (2.05%)
occurrences all number	2	3
Haematemesis
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Nausea
subjects affected / exposed	1 / 126 (0.79%)	1 / 146 (0.68%)
occurrences all number	1	1
Pancreatitis
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Paraesthesia oral
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Rectal haemorrhage
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Tongue discolouration
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Vomiting
subjects affected / exposed	3 / 126 (2.38%)	0 / 146 (0.00%)
occurrences all number	3	0
Skin and subcutaneous tissue disorders
Dermatitis diaper
subjects affected / exposed	1 / 126 (0.79%)	1 / 146 (0.68%)
occurrences all number	1	1
Dry skin
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Eczema
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Onychoclasis
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Petechiae
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Photosensitivity reaction
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Rash
subjects affected / exposed	2 / 126 (1.59%)	1 / 146 (0.68%)
occurrences all number	2	1
Skin discolouration
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Urticaria
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Renal and urinary disorders
Dysuria
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Polyuria
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 126 (0.00%)	3 / 146 (2.05%)
occurrences all number	0	3
Back pain
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Flank pain
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Limb discomfort
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Musculoskeletal chest pain
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Musculoskeletal stiffness
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Myalgia
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Pain in extremity
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Tendonitis
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Infections and infestations
Bacterial disease carrier
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Bronchopulmonary aspergillosis allergic
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Candida infection
subjects affected / exposed	1 / 126 (0.79%)	5 / 146 (3.42%)
occurrences all number	1	5
Conjunctivitis
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Eczema infected
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Eye infection
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Foot and mouth disease
subjects affected / exposed	0 / 126 (0.00%)	2 / 146 (1.37%)
occurrences all number	0	2
Gastroenteritis
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Haemophilus infection
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	2	0
Infectious mononucleosis
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Infective pulmonary exacerbation of cystic fibrosis
subjects affected / exposed	3 / 126 (2.38%)	6 / 146 (4.11%)
occurrences all number	4	6
Lower respiratory tract infection
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Mycobacterium avium complex infection
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Nasopharyngitis
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Oral candidiasis
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Otitis media
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Pneumonia
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Pseudomonas infection
subjects affected / exposed	7 / 126 (5.56%)	2 / 146 (1.37%)
occurrences all number	7	2
Respiratory tract infection
subjects affected / exposed	1 / 126 (0.79%)	2 / 146 (1.37%)
occurrences all number	1	2
Sinusitis
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Upper respiratory tract infection
subjects affected / exposed	11 / 126 (8.73%)	2 / 146 (1.37%)
occurrences all number	15	3
Urinary tract infection
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Varicella
subjects affected / exposed	3 / 126 (2.38%)	1 / 146 (0.68%)
occurrences all number	3	1
Viral infection
subjects affected / exposed	1 / 126 (0.79%)	1 / 146 (0.68%)
occurrences all number	1	1
Vulvovaginal candidiasis
subjects affected / exposed	2 / 126 (1.59%)	0 / 146 (0.00%)
occurrences all number	2	0
Nasal vestibulitis
subjects affected / exposed	1 / 126 (0.79%)	0 / 146 (0.00%)
occurrences all number	1	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Vitamin A deficiency
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Vitamin D deficiency
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1
Vitamin E deficiency
subjects affected / exposed	0 / 126 (0.00%)	1 / 146 (0.68%)
occurrences all number	0	1

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

15 Feb 2010

V2.0 (15/2/2010): A complete list of amendments and clarifications have been attached in a seperate document.

01 Sep 2010

V3.0 (1/9/2010) Page Number Amendment Comment Throughout Updated version and date; correction of typographical errors 5 Addition of Miss Joanne Eatock, Senior Data Manager 9 Updated the table of contents 11 List of abbreviations updated Throughout Clarification text added to Exclusion criteria 4. ‘Please note, short courses of oral ciprofloxacin or intravenous antibiotics (with an anti-pseudomonal spectrum of action) are not an exclusion unless they are given to treat proven infections with P. aeruginosa’ Throughout Primary endpoint text amended from ‘Successful eradication of P. aeruginosa infection at three months post randomisation, remaining infection free through to 15 months post randomisation’ changed to read ‘Successful eradication of P. aeruginosa infection at three months post treatment, remaining infection free through to 15 months post treatment’ Throughout Secondary endpoint 8 changed from ‘Number of days spent as inpatient in hospital over the three-month period post-treatment and between three months and 15 months post-treatment (other than 14 days spent on initial IV treatment)’ to ‘Number of days spent as inpatient in hospital over the three-month period post-randomisation and between three months and 15 months post-randomisation (other than 14 days spent on initial IV treatment)’ 16 Section 1.3 text ‘post randomisation’ changed to ‘post treatment’ 21 Section 4.3.3 text ‘ Premature Discontinuation’ changed to ‘Withdrawal’ 22 Details for the web randomisation system changed 23 Section 6.1 text ‘designed as a’ replaced with ‘a phase IV’ 23-30 Formal accountability procedures for the trial along with labelling requirements removed and section updated to detail informal accountability introduced to monitor treatment compliance 31-32 Section 35 Addition of guidance table for administration of Questionnaire Booklets 41 Change to the wording of the CACE study to reflect changes in the ethics approved protocol 43 Section 8.4 tex

13 Dec 2010

V4.0 (13/12/2010) A complete list of amendments and clarifications have been attached in a seperate document

11 Jan 2012

V5.0 (11/01/2012) Page Number Amendment Comment Throughout Updated version and date; correction of typographical errors 24 Section 6.3.3 changed from ‘Home Care companies can be used to provide Home IVs only if the CTU is provided with a copy of the companies MIAIMP licence as part of the green light process.’ to ‘Homecare companies can be used. Homecare companies that reconstitute intravenous medicines centrally and supply reconstituted injectables directly to patient's home must be a registered pharmacy. In addition, the IMPs shall be dispensed to a subject in accordance with a prescription given by an authorised health care professional and labelled in accordance with the requirements that apply to dispensed relevant medicinal products.’

17 Oct 2013

V6.0 (17/10/2013) : A complete list of amendments and clarifications have been attached in a seperate document.

12 Aug 2014

V7.0 (12/08/2014) Page Number Amendment Comment Throughout Updated version and date Throughout Updated contact details 9 - 10 Updated table of contents Throughout Replacement of Medicines for Children Research Network with Medicines for Children Throughout Participating sites to include international sites Throughout Addition of University of Liverpool as Co-Sponsor; they will act as sole sponsor for international sites 11 Study period changed from 6 years and 3 months to 8 years and 7 months 22 Section 4.3.1 changed requirement for follow-up via GP where the participant moves to a non-particpiating site. Replaced with: “Where this is not possible, if the participant is still happy for their data to be collected, the recruiting centre should make every effort to obtain data collected as part of routine care from the centre that is now responsible for the participants care.” 39 Section 7.6 Added sentence: “At the time of database lock, data entry privileges are withdrawn from the trial database.” 61 Section 14 Details of financial arrangements removed, described separately in the contracts.

23 Dec 2015

V8.0 (23/12/2015) Page Number Amendment Comment Throughout Updated version and date 9 - 10 Updated table of contents Throughout Clarifying follow-up period; patients who start randomised treatment before 1st January 2016 will continue follow-up for 24 months, patients who start randomised treatment on or after 1st January 2016 will continue follow-up for 15 months. 27 Text changed from “Ceftazidime 150 milligram (mg)/kilogram (kg)/day, in 3 divided doses (maximum of 3 grams (g) three times daily (tds)). Some centres may use a twice daily regimen for ceftazidime. These centres may continue to use this regimen for the study and should follow their local dosing guidelines.” To “Ceftazidime 150 milligram (mg)/kilogram (kg)/day, in 3 divided doses (maximum of 3 grams (g) three times daily (tds)). Some centres may use a once daily continuous infusion (where the maximum daily dose would usually be 6g/day) or twice daily regimen for ceftazidime. These centres may continue to use this regimen for the study and should follow their local dosing guidelines.” 42 Clarification of genotyping arrangement outside the UK - 45 Corrected typrographical error inserting “serious” in section 9.5 to correct text to say “Expectedness should be assessed for all serious adverse reactions” 63 Removed reference to supllementary document describing indemnity arrnagemnets for non-Uk sites. Replaced with “Equivalent cover to that provided by the Clinical Negligence Scheme for UK Trusts should be confirmed to be in place for non-UK sites during site suitability assessment and cover summarised in the sponsor-site contract.”

12 Dec 2016

V9.0 (12/10/2016) Page Number Amendment Comment Throughout Updated version and date 11 Updated number of patients to be enrolled

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: Trial of Optimal Therapy for Pseudomonas Eradication in Cystic Fibrosis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Primary efficacy assessment - Successful eradication of P. aeruginosa three months after the start of treatment, remaining infection free through to 15 months after the start of treatment

Primary: Primary efficacy assessment - Successful eradication of P. aeruginosa three months after the start of treatment, remaining infection free through to 15 months after the start of treatment

Primary: Primary efficacy assessment - Successful eradication of P. aeruginosa three months after the start of treatment, remaining infection free through to 15 months after the start of treatment

Primary: Primary efficacy assessment - Successful eradication of P. aeruginosa three months after the start of treatment, remaining infection free through to 15 months after the start of treatment

Primary: Primary efficacy assessment – Sensitivity analysis 6: no T15 window (Post hoc)

Primary: Primary efficacy assessment – Sensitivity analysis 6: no T15 window (Post hoc)

Secondary: Time to reoccurrence of original P.aeruginosa infection - unknown strains assumed to be same as baseline

Secondary: Time to reoccurrence of original P.aeruginosa infection - unknown strains assumed to be same as baseline

Secondary: Time to reoccurrence of original P.aeruginosa infection - unknown strains assumed to be different to baseline

Secondary: Time to reoccurrence of original P.aeruginosa infection - unknown strains assumed to be different to baseline

Secondary: Re-infection with a different strain of P.aeruginosa

Secondary: Re-infection with a different strain of P.aeruginosa

Secondary: Post hoc analysis – Genotyping results

Secondary: Post hoc analysis – Genotyping results

Secondary: Lung function - FEV1% predicted

Secondary: Lung function - FEV1% predicted

Secondary: Lung function - FVC% predicted

Secondary: Lung function - FVC% predicted

Secondary: Lung function - FEF25-75% predicted

Secondary: Lung function - FEF25-75% predicted

Secondary: Oxygen saturation

Secondary: Oxygen saturation

Secondary: Growth and nutritional status - Height z-scores

Secondary: Growth and nutritional status - Height z-scores

Secondary: Growth and nutritional status - Weight z-scores

Secondary: Growth and nutritional status - Weight z-scores

Secondary: Growth and nutritional status - BMI z-scores

Secondary: Growth and nutritional status - BMI z-scores

Secondary: Growth and nutritional status - BMI

Secondary: Growth and nutritional status - BMI

Secondary: Number of pulmonary exacerbations - median number of exacerbations during the 15 months following treatment commencement

Secondary: Number of pulmonary exacerbations - median number of exacerbations during the 15 months following treatment commencement

Secondary: Number of pulmonary exacerbations - Number of participants experiencing at least one exacerbation during the first 15 months of follow up

Secondary: Number of pulmonary exacerbations - Number of participants experiencing at least one exacerbation during the first 15 months of follow up

Secondary: Admission to hospital - Number of participants experiencing at least one hospital stay during the first 3 months of treatment

Secondary: Admission to hospital - Number of participants experiencing at least one hospital stay during the first 3 months of treatment

Secondary: Admission to hospital - Number of participants experiencing at least one hospital stay during the 12 months following treatment

Secondary: Admission to hospital - Number of participants experiencing at least one hospital stay during the 12 months following treatment

Secondary: Admission to hospital - Number of participants experiencing at least one hospital stay between 15 and 24 months

Secondary: Admission to hospital - Number of participants experiencing at least one hospital stay between 15 and 24 months

Secondary: Number of days spent as an inpatient in hospital - During treatment phase

Secondary: Number of days spent as an inpatient in hospital - During treatment phase

Secondary: Number of days spent as an inpatient in hospital - During the 12 months post treatment phase

Secondary: Number of days spent as an inpatient in hospital - During the 12 months post treatment phase

Secondary: Number of days spent as an inpatient in hospital - between 15 and 24 months follow up

Secondary: Number of days spent as an inpatient in hospital - between 15 and 24 months follow up

Secondary: CFQ - Physical functioning – Self Report

Secondary: CFQ - Physical functioning – Self Report

Secondary: CFQ - Role/school functioning – Self Report

Secondary: CFQ - Role/school functioning – Self Report

Secondary: CFQ - Vitality – Self Report

Secondary: CFQ - Vitality – Self Report

Secondary: CFQ - Emotional functioning – Self Report

Secondary: CFQ - Emotional functioning – Self Report

Secondary: CFQ - Social functioning – Self Report

Secondary: CFQ - Social functioning – Self Report

Secondary: CFQ - Body Image – Self Report

Secondary: CFQ - Body Image – Self Report

Secondary: CFQ - Eating Problems – Self Report

Secondary: CFQ - Eating Problems – Self Report

Secondary: CFQ - Treatment Burden – Self Report

Secondary: CFQ - Treatment Burden – Self Report

Secondary: CFQ - Health Perceptions – Self Report

Secondary: CFQ - Health Perceptions – Self Report

Secondary: CFQ - Weight – Self Report

Secondary: CFQ - Weight – Self Report

Secondary: CFQ - Respiratory Symptoms – Self Report

Secondary: CFQ - Respiratory Symptoms – Self Report

Secondary: CFQ - Digestive Symptoms – Self Report

Secondary: CFQ - Digestive Symptoms – Self Report

Clinical Trial Results:
Trial of Optimal Therapy for Pseudomonas Eradication in Cystic Fibrosis