Optimizing Care for Children Hospitalized With Community-acquired Pneumonia: Novel Diagnostics

Study Overview
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Brief Summary
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Children are commonly hospitalized because of community-acquired pneumonia. Despite the fact that many of these children have viral disease, a majority is treated with antibiotics. These antibiotics will not accelerate recovery in those with viral pneumonia and can cause harm. We are interested in exploring whether the MeMed BV - a composite biomarker assay - could be used to improve antibiotic prescribing in these children by identifying those who likely have viral disease. This proposal describes a feasibility randomized trial of this diagnostic intervention.

Official Title
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Optimizing Care for Children Hospitalized With Community-acquired Pneumonia: a Feasibility Randomized Controlled Trial of a Diagnostic Intervention

Conditions
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Community-acquired Pneumonia

Intervention / Treatment
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* Diagnostic Test: MeMed BV + Usual Care
* Other: Usual Care Alone


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 from if they have received >48h of intravenous antibiotics (eg. if transferred from another healthcare facility) or if they have a lobar consolidation that occupies the majority of a lobe on imaging, a pleural effusion that occupies more than ¼ of a lung field, or a positive blood culture for a bacterial pathogen (not a contaminant). Examples of CAP pathogens include S. pneumoniae, S. pyogenes (group A streptococcus), S. aureus, S. anginosus. Examples of contaminants that would be ignored include the coagulase-negative staphylococci and Bacillus spp. 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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants randomized to usual care or usual care + diagnostic intervention.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MeMed BV<br> | Diagnostic Test: MeMed BV + Usual Care<br>* We will aim to have blood drawn for MeMed BV testing within 24 hours of the first dose of IV antibiotics. We will then aim to have test results back within 24 hours of sampling.<br>|
| Active Comparator: Usual Care<br> | Other: Usual Care Alone<br>* Usual care can involve oxygenation support, ventilatory support, intravenous fluids, and antibiotics, or any combination of these.<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 | 
| MeMed BV test timing | The proportion of participants randomized to the diagnostic intervention who successfully have the MeMed BV performed within 24 h of receipt of the initial dose of IV antibiotics | before Day 2 | 
| MeMed BV test result reporting | The proportion of participants randomized to MeMed BV testing that have a test result available within 48h of sampling | before Day 3 | 
| MeMed BV test result initial adherence | The proportion of participants found to be high risk for viral infection that successfully have their antibiotics stopped within 24 hours of the test result becoming available | before Day 4 | 
| MeMed BV test result delayed adherence | The proportion of participants (who successfully had their antibiotics stopped) that do not have them restarted specifically for CAP treatment prior to discharge | before Day 15 | 
| Losses to followup | The proportion of participants lost to follow-up | before Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early clinical response | This is defined as: i) clinical improvement in fever, work of breathing, oral intake, and activity level, AND ii) lack of receipt of additional antimicrobials beyond those already being given at baseline (for the control group) or as indicated by MeMed BV testing (for those randomized to the intervention group) | Day 4 | 
| Days of antibiotics given specifically for CAP before hospital discharge |  | Before discharge | 
| Days of antibiotics given specifically for CAP after hospital discharge and before day 30 |  | after hospital discharge and before day 30 | 
| Time to resolution of fever |  | Before discharge | 
| Time to resolution of difficulty breathing |  | Before discharge | 
| Time to resolution of hypoxaemia |  | Before discharge | 
| Length of stay in hospital |  | Before discharge | 
| Repeat hospitalization for CAP |  | After discharge and before day 30 | 
| Unscheduled ED or urgent care visits |  | After discharge and before day 30 | 
| Unscheduled primary care visits |  | After discharge and before day 30 | 
| Development of complicated pneumonia | Complicated defined by effusion, empyaema, necrotizing pneumonia | Before Day 30 | 
| Acceptability of care plan to caregiver |  | Baseline | 
| Acceptability of care plan to caregiver |  | Day 30 |