Clinical Trial Results:
Pseudomonas aeruginosa eradication in patients with cystic fibrosis: a randomised multicentre study comparing classic treatment protocols with classic treatment together with antibiotic treatment of upper airways.
Summary
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EudraCT number |
2015-003881-96 |
Trial protocol |
IT |
Global end of trial date |
08 Jan 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Aug 2021
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First version publication date |
04 Aug 2021
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
EPAFC
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
AZIENDA OSPEDALIERO UNIVERSITARIA MEYER
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Sponsor organisation address |
VIALE PIERACCINI 24, FIRENZE, Italy, 50139
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Public contact |
FIBROSI CISTICA, AZIENDA OSPEDALIERO UNIVERSITARIA MEYER, +39 0555662474, giovanni.taccetti@meyer.it
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Scientific contact |
FIBROSI CISTICA, AZIENDA OSPEDALIERO UNIVERSITARIA MEYER, +39 0555662474, giovanni.taccetti@meyer.it
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
30 Sep 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
08 Jan 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
08 Jan 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the efficacy (P. aeruginosa eradication from the lower airways) of two types of treatment in Cystic Fibrosis (CF) patients: the classic eradication protocol used until now (treatment A), versus the classic protocol together with nasal lavage with colistin (treatment B).
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Protection of trial subjects |
No specific risks, pain or distress were expected for the trial subjects. Moreover, risks were comparable to that observed in clinical practice. No specific measures were put in place for trial subjects.
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Background therapy |
The following treatments were approved as efficacious standard therapy for the eradication of Pseudomonas Aeruginosa in the lower airways of CF patients: a) Inhalation of colistin (2.000.000 UI or 1.000.000 UI if I-NEB® is used) b.i.d. (total daily dose 4.000.000 IU) and 30 mg/kg/day of oral ciprofloxacin divided into 2 doses for 4 weeks (maximum daily dose 750 mg x 2); b) Inhalation of tobramycin, 300 mg twice daily (600 mg total daily dose) for 4 weeks with appropriate nebulizers; c) Aztreonam lysine for inhalation, 75 mg three times daily (total daily dose 225 mg) for 4 weeks with appropriate nebulizers | ||
Evidence for comparator |
No active comparator or placebo were used in this trial. | ||
Actual start date of recruitment |
01 May 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Italy: 51
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Worldwide total number of subjects |
51
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EEA total number of subjects |
51
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
32
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Adolescents (12-17 years) |
8
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Adults (18-64 years) |
11
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The recruitment period lasted 2 years. | |||||||||||||||||||||
Pre-assignment
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Screening details |
All the screened patients (n=51) were enrolled in the study. | |||||||||||||||||||||
Period 1
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Period 1 title |
Study period (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Standard of care - A | |||||||||||||||||||||
Arm description |
Enrolled patients received the classic eradication therapy as per standard of care | |||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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Experimental - B | |||||||||||||||||||||
Arm description |
Enrolled patients received the classic eradication therapy as per standard of care with nasal lavage with colistin. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Colistin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate and solvent for solution for injection
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Routes of administration |
External use
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Dosage and administration details |
Nasal irrigation with colistin 2.000.000 U b.i.d (total daily dose 4.000.000 IU) for a period of 4 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Standard of care - A
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Reporting group description |
Enrolled patients received the classic eradication therapy as per standard of care | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Experimental - B
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Reporting group description |
Enrolled patients received the classic eradication therapy as per standard of care with nasal lavage with colistin. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Standard of care - A
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Reporting group description |
Enrolled patients received the classic eradication therapy as per standard of care | ||
Reporting group title |
Experimental - B
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Reporting group description |
Enrolled patients received the classic eradication therapy as per standard of care with nasal lavage with colistin. |
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End point title |
Difference in P. aeruginosa eradication from the lower airways in the two treatment groups (A and B). Eradication is defined as 3 negative, successive P. aeruginosa cultures within 6 months | |||||||||||||||
End point description |
Difference in P. aeruginosa eradication from the lower airways in the two treatment groups (A and B). Eradication is defined as 3 negative, successive P. aeruginosa cultures within 6 months
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End point type |
Primary
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End point timeframe |
6 months
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Notes [1] - According to the intention to treat analysis dropped-out patients were included [2] - According to the intention to treat analysis dropped-out patients were included |
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Statistical analysis title |
Primary endpoint | |||||||||||||||
Comparison groups |
Standard of care - A v Experimental - B
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Number of subjects included in analysis |
51
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Analysis specification |
Pre-specified
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Analysis type |
superiority [3] | |||||||||||||||
Method |
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Parameter type |
Risk difference (RD) | |||||||||||||||
Point estimate |
10.15
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
1-sided
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lower limit |
-16.7 | |||||||||||||||
upper limit |
- | |||||||||||||||
Notes [3] - Intention to treat analysis was conducted and patients dropped-out were considered as treatment failure |
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End point title |
P. Aeruginosa recurrence risk | |||||||||||||||
End point description |
We estimated the P. aeruginosa recurrence risk in the two groups and relative risk
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End point type |
Primary
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End point timeframe |
6 months
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Notes [4] - According to the intention to treat analysis dropped-out patients were included [5] - According to the intention to treat analysis dropped-out patients were included |
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Statistical analysis title |
Primary endpoint | |||||||||||||||
Statistical analysis description |
We estimated the risk of recurrence in the Group B and the risk of recurrence in the Group A.
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Comparison groups |
Standard of care - A v Experimental - B
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Number of subjects included in analysis |
51
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||
Method |
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Parameter type |
Risk ratio (RR) | |||||||||||||||
Point estimate |
1.28
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
1-sided
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lower limit |
0.7 | |||||||||||||||
upper limit |
- |
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Adverse events information
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Timeframe for reporting adverse events |
Treatment period (28 days) and 6-months follow-up
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||
Dictionary version |
22.0
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Reporting groups
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Reporting group title |
Experimental group - B
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Reporting group description |
Subjects in the experimental group received the classic eradication therapy as per standard of care with nasal lavage with colistin. | |||||||||||||||||||||||||||||||||
Reporting group title |
Standard of care group - A
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Reporting group description |
Subjects in the standard of care group received the classic eradication therapy. | |||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
This study is under-powered as the trial did not enrol the initial estimated sample. |