Clinical Trial Results:
Antibiotics for lower Respiratory Tract Infection in Children presenting in Primary Care
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Summary
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EudraCT number |
2015-002455-97 |
Trial protocol |
GB |
Global end of trial date |
17 Apr 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
18 Dec 2021
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First version publication date |
18 Dec 2021
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Other versions |
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Summary report(s) |
Antibiotics for lower respiratory tract infection in children presenting in primary care in England (ARTIC PC): a double-blind, randomised, placebo-controlled trial |
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 |
13381
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Additional study identifiers
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ISRCTN number |
ISRCTN79914298 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Sponsor R&D reference: 13381 | ||
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Sponsors
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Sponsor organisation name |
University of Southampton
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Sponsor organisation address |
University Road, Southampton, United Kingdom, SO17 1BJ
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Public contact |
Paul Little, University of Southampton, 0044 02380241050, p.little@soton.ac.uk
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Scientific contact |
Paul Little, University of Southampton, 0044 02380241050, p.little@soton.ac.uk
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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 |
29 Jun 2020
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
17 Apr 2020
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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 |
Our aim is to provide evidence to inform the use of antibiotics for the management of chest infections in children. The objectives are:
1) To estimate the effectiveness of amoxicillin overall and in key clinical subgroups of children presenting with uncomplicated (non-pneumonic) lower respiratory tract infection in primary care
2) To estimate the cost-effectiveness of antibiotics overall and in key clinical subgroups of children presenting with uncomplicated lower respiratory tract infection in primary care
3) To explore the estimates of effectiveness according to key pathophysiological subgroups ( the presence of bacterial pathogens; raised C reactive protein measurement or white cell count; the presence of clinically undetected consolidation on X ray; oximetry; lung function)
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Protection of trial subjects |
None
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Aug 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 |
United Kingdom: 438
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Worldwide total number of subjects |
438
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EEA total number of subjects |
0
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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) |
438
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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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 study was a randomised control trial (placebo vs amoxicillin) carried out in a Primary Care setting, investigating the effectiveness of amoxicillin in treating lower respiratory tract infections in Children (6mth to 12 yrs). | |||||||||
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Pre-assignment
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Screening details |
Inclusion criteria: Acute uncomplicated LRTI (acute cough as the most prominent symptom and lower tract symptoms/signs (sputum/’rattly chest’/coarse rhonchi; breathless; pain). Exclusion criteria: Non-infective (e.g. reflux, Pulmonary Embolism (PE)) or croup (where viral aetiology is very likely). | |||||||||
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Period 1
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Period 1 title |
Overall (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Data analyst | |||||||||
Blinding implementation details |
Randomisation will per pts will be either antibiotic or placebo. The clinician will dispense sequentially numbered pre-prepared randomised packs. The randomisation codes for antibiotic or placebo will be kept by the manufacturer and with a dedicated unblinding service.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | |||||||||
Arm description |
Amoxicillin placebo. Oral suspension. Powder for reconstitution. | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
250mg/5ml. Dosing as follows:
Weight (kg) Dose (for oral administration) Duration
4.5 to <6.5 100mg (2ml) TDS 7 days
6.5 to <9 150mg (3ml) TDS 7 days
9 to <12 200mg (4ml) TDS 7 days
12 to <15 250mg (5ml) TDS 7 days
15 to <18 300mg (6ml) TDS 7 days
18 to <24 400mg (8ml) TDS 7 days
24 to <30 500mg (10ml) TDS 7 days
30 to <36 600mg (12ml) TDS 7 days
36 + 700mg (14ml) TDS 7 days
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Arm title
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Amoxicillin | |||||||||
Arm description |
Oral suspension, 250mg/5ml of amoxicillin. Powder for reconstitution. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Amoxicillin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
250mg/5ml. Dosing as follows:
Weight (kg) Dose (for oral administration) Duration
4.5 to <6.5 100mg (2ml) TDS 7 days
6.5 to <9 150mg (3ml) TDS 7 days
9 to <12 200mg (4ml) TDS 7 days
12 to <15 250mg (5ml) TDS 7 days
15 to <18 300mg (6ml) TDS 7 days
18 to <24 400mg (8ml) TDS 7 days
24 to <30 500mg (10ml) TDS 7 days
30 to <36 600mg (12ml) TDS 7 days
36 + 700mg (14ml) TDS 7 days
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 6 pts withdrew the use of their data. |
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Amoxicillin placebo. Oral suspension. Powder for reconstitution. | ||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Amoxicillin
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Reporting group description |
Oral suspension, 250mg/5ml of amoxicillin. Powder for reconstitution. | ||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Amoxicillin placebo. Oral suspension. Powder for reconstitution. | ||
Reporting group title |
Amoxicillin
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Reporting group description |
Oral suspension, 250mg/5ml of amoxicillin. Powder for reconstitution. | ||
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End point title |
PRIMARY: Mean duration of symptoms rated less than moderately bad or worse | |||||||||
End point description |
The length of time (mean) symptoms were rated less than moderately bad or worse on the follow up questionnaire.
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End point type |
Primary
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End point timeframe |
Maximum 28 days.
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Statistical analysis title |
Primary Outcome | |||||||||
Statistical analysis description |
Cox regression was used for the primary outcome (duration of symptoms rated moderately bad or worse in days) and for total symptom duration, adjusting for age, baseline symptom severity, previous duration of illness and comorbidity. Multiple imputation was chosen for the primary analysis because multiple imputation is generally more efficient than complete case analysis and particularly important to control for potential for potential attrition bias.
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Comparison groups |
Placebo v Amoxicillin
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Number of subjects included in analysis |
317
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||
P-value |
< 0.05 | |||||||||
Method |
Regression, Cox | |||||||||
Parameter type |
Hazard ratio (HR) | |||||||||
Point estimate |
1.13
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.92 | |||||||||
upper limit |
1.42 | |||||||||
Variability estimate |
Standard deviation
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Adverse events information [1]
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Timeframe for reporting adverse events |
Serious Adverse Events are to be reported to Study Team with 24 hours of site staff becoming aware. The Chief Investigator (CI) or their designated representative will be responsible for assessing the expectedness of SAEs reported.
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Adverse event reporting additional description |
Amoxicillin is a licensed medicine whose most common side-effects are mucocutaneous candidosis (thrush), diarrhoea, nausea, vomiting and rash (occurrence >=1/100 to <1/10). If these occur and are non-serious and of mild to moderate severity (based on clinician’s assessment) an Adverse Event Report form will not be necessary. We will collect data on
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Assessment type |
Systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
none | ||
Dictionary version |
0
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| Frequency threshold for reporting non-serious adverse events: 0% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Amoxicillin is a licensed medicine whose most common side-effects are mucocutaneous candidosis (thrush), diarrhoea, nausea, vomiting and rash (occurrence >=1/100 to <1/10). If these occur and are non-serious and of mild to moderate severity (based on clinician’s assessment) an Adverse Event Report form will not be necessary. We will collect data on severe reactions. |
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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. | |||
| None reported | |||
