Optimizing Care for Children Hospitalized With Community-acquired Pneumonia: Short-course Therapy

Study Overview
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Brief Summary
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Children are commonly hospitalized because of community-acquired pneumonia (CAP). There are multiple high-quality randomized trials of short-course antibiotic therapy (3-5 days of treatment) for adults hospitalized with CAP - but there is very little evidence in children. We intend to do a pilot RCT of short-course (3-5 days) vs standard-duration (8-10 days) antibiotic therapy for children hospitalized for CAP.

Official Title
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Optimizing Care for Children Hospitalized With Community-acquired Pneumonia: a Feasibility Randomized Controlled Trial of Short-course Antibiotic Therapy

Conditions
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Community-acquired Pneumonia

Intervention / Treatment
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* Drug: Placebo
* Drug: Amoxicillin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - children with a history of fever who are hospitalized with CAP (ie. 'severe CAP') as per the clinical team and who have abnormal chest imaging (eg. radiograph, ultrasound) will be eligible. They must also have at least one of the following: documented tachypnoea (>60 bpm for age <1 y, >50 bpm for 1-2 y, >40 bpm for 2-4 y, and >30 bpm for >4 y); cough on exam or by history; increased work of breathing on exam; or auscultatory findings (eg. focal crackles, bronchial breathing) consistent with CAP. Exclusion Criteria: Children will be excluded if: antibiotics have been discontinued; they received >3 days of effective antibiotic treatment (excluding macrolide treatment) prior to hospitalization; there is supplemental oxygen use or fever within the past 24 h; more than 5 days elapsed since admission; the attending clinical team does not wish to use oral amoxicillin for treatment (because of allergy or any other reason); or the child is taking coumadin-based anticoagulants or tetracycline-type antibiotics (because of potential interactions with amoxicillin). Children will also be excluded if they have any of the following: chronic lung disease, congenital heart disease (requiring treatment or with exercise restrictions), malignancy, immunodeficiency (primary, acquired, or iatrogenic), a separate episode of pneumonia previously diagnosed within the past 2 weeks, or lung abscess diagnosed within the past six months. Children will not be eligible to participate more than once.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 18 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 treatment<br>5 days of placebo (after participants already received 3-5 days of antibiotics) | Drug: Placebo<br>* 5 days of placebo to be given after 3-5 days of antibiotics<br>|
| Active Comparator: Standard-duration treatment<br>5 days of amoxicillin (after participants already received 3-5 days of antibiotics) | Drug: Amoxicillin<br>* Standard-dose amoxicillin (approved by Health Canada) to be given x 5 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Consent success | The proportion of potentially eligible participants who consent | Day 0 | 
| Open-label antibiotic use | The proportion of participants who receive open-label (non-study) antibiotics | before Day 30 | 
| Losses to followup | The proportion of participants lost to follow-up | before Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with late clinical response | LCR is defined as: i) clinical improvement in fever, work of breathing, oral intake, and activity level, AND ii) lack of receipt of additional antimicrobials | Day 15 | 
| Proportion of participants with repeat hospitalization for CAP |  | before Day 30 | 
| Proportion of participants with drug-related AEs (any severity) |  | before Day 30 | 
| Proportion of participants with serious drug AEs |  | before Day 30 | 
| Proportion of participants with unscheduled ED or urgent care visits |  | before Day 30 | 
| Proportion of participants with unscheduled primary care visits |  | before Day 30 | 
| Proportion of participants who develop complicated pneumonia | Complicated defined by effusion, empyaema, necrotizing pneumonia | before Day 30 |