Short-course Antimicrobial Therapy for Paediatric Respiratory Infections

Study Overview
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Brief Summary
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Randomized controlled double-blind non-inferiority clinical trial to determine whether five days of high-dose amoxicillin leads to comparable rates of early clinical cure compared with 10 days of high-dose amoxicillin for previously healthy children with mild community-acquired pneumonia.

Official Title
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Short-course Antimicrobial Therapy for Paediatric Respiratory Infections

Conditions
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Community-acquired Pneumonia

Intervention / Treatment
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* Drug: Amoxicillin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children aged 6 months to 10 years presenting with CAP will be eligible. CAP will be defined if all of the four following numeric criteria are met: fever (>37.5 C axillary, > 37.7 C oral, or >38 C rectal) recorded in the ED or at home in the 48h prior to presentation; any one of: tachypnoea on exam (>60 bpm for age <1 y, >50 bpm for 1-2 y of age, >40 bpm for 2-4 y of age, and >30 bpm for >4 y of age); cough on exam or by history; increased work of breathing on exam; or auscultatory findings (focal crackles, bronchial breathing, etc.) consistent with pneumonia; infiltrates on chest radiograph consistent with bacterial CAP as judged by the ED physician; and the attending ED physician diagnoses the child with primary CAP. (Children treated with systemic steroids in the ED will be presumed to have primary asthma exacerbation with possible infection and therefore will not meet inclusion criteria.) Participants must be well enough to be treated as outpatients (discharged home by the ED physician, adequate volume status, able to tolerate oral medication, oxygen saturation > 90%, no evidence of impending respiratory failure), and have no evidence of empyaema or necrotizing pneumonia on chest radiograph. Exclusion Criteria: Children will be excluded if they have any of the following: cystic fibrosis, anatomic lung disease, bronchiectasis, congenital heart disease, history of repeated aspiration or velopharyngeal incompetence, malignancy, conditions requiring treatment with immune suppressants, primary immunodeficiency, advanced HIV infection, prolonged admissions (>48 h) to hospital within the past 2 months, pneumonia previously diagnosed within the past month, lung abscess diagnosed within the past six months, receipt of > 24 hours of beta-lactam antibiotic therapy already received at presentation to the ED, receipt of at least a 5 day course of amoxicillin < 72h prior to presenting to the ED, receipt of an intravenous cephalosporin or azithromycin in the ED, or suspected allergy to penicillin. Children will not be eligible to participate more than once.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Short-course<br>5 days amoxicillin 90 mg/kg/day divided TID followed by 5 days placebo TID | Drug: Amoxicillin<br> <br> * Other names: Amoxil;Drug: Placebo<br>* Experimental arm must receive 5 days placebo after 5 days amoxicillin to preserve blinding.<br>|
| Active Comparator: Standard<br>5 days amoxicillin 90 mg/kg/day divided TID followed by alternate formulation 5 days amoxicillin 90 mg/kg/day divided TID | Drug: Amoxicillin<br> <br> * Other names: Amoxil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early clinical cure (Resolution of tachypnoea, increased work of breathing, and fever) | Resolution of tachypnoea, increased work of breathing, and fever | at 14-21 days post-enrolment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days of adverse reactions |  | up to 14 days post-enrolment | 
| Days of missed school |  | up to 14 days post-enrolment | 
| Days of missed/disrupted work for caregiver(s) |  | up to 14 days post-enrolment | 
| Adherence to study medications |  | up to 10 days post-enrolment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antibiotic stewardship, non-inferiority, randomized controlled trial