Hospitalised Pneumonia With Extended Treatment (HOPE) Study

Study Overview
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Brief Summary
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An intervention study to determine if a longer duration of antibiotics (compared to shorter duration) improves the short and long term clinical outcomes of children hospitalised for pneumonia

Detailed Description
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A multi-centre double-blind randomised controlled trial to determine if a longer duration of amoxicillin-clavulanic acid (compared to shorter duration) improves the short and long term clinical outcomes of children hospitalised with community-acquired pneumonia, in Indigenous children and a developing country

Official Title
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A Multi-centre Double-blind Randomised Controlled Trial to Determine if a Longer Duration of Amoxicillin-clavulanic Acid (Compared to Shorter Duration) Improves Clinical Outcomes of Children Hospitalised With Community-acquired Pneumonia

Conditions
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Pneumonia

Intervention / Treatment
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* Drug: Amoxicillin-clavulanic Acid
* Drug: Placebo (for Amoxicillin-clavulanic Acid)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hospitalised children aged 3-mo to 5-yrs (in Darwin, children have to be Indigenous) Have features of severe pneumonia on admission (temperature >37.5 celsius or a history of fever at home or observed at the referring clinic, age-adjusted tachypnoea [respiratory rate>50 if <12-months; respiratory rate>40 if >12-months] with chest wall recession and/or oxygen saturation <92% in air), and consolidation on chest X-ray as diagnosed by treating clinician After 1-3 days of IV antibiotics, are afebrile, with improved respiratory symptoms and signs, oxygen saturation>90% in air and are ready to be switched to oral amoxicillin-clavulanate, and Have symptoms of no longer than 7 days at point of hospitalisation. Exclusion Criteria: Current wheeze Underlying chronic illness other than asthma (e.g. bronchiectasis, cyanotic congenital heart disease or cardiac failure, neuromuscular disorders, immunodeficiency) that could potentially influence the current illness Severe malnutrition (weight-for-height Z-score <-3) Complicated (effusion, empyema or abscess) pneumonia, including tuberculosis Extra-pulmonary infection requiring antibiotic therapy (e.g. meningitis) Beta-lactam allergy Previously enrolled Lack a mobile phone and/or unable to return for follow-up clinic visits during the next 24 months

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 5 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: Active arm: Amoxicillin-clavulanic Acid<br>8 days of oral amoxicillin-clavulanic Acid 400/57 duo formulation (70-90mg/kg/day, twice daily dosing: max 980mg per day) | Drug: Amoxicillin-clavulanic Acid<br> <br> |
| Placebo Comparator: Placebo arm<br>8 days of oral placebo (equivalent volume as the active arm) | Drug: Placebo (for Amoxicillin-clavulanic Acid)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion without chronic respiratory symptoms and signs or bronchiectasis. | Any further chronic respiratory symptoms and signs or bronchiectasis though the child's medical records (community or hospital) will be captured. These children will be reviewed at 24 months, however many children will reside in geographically isolated locations, thus a range of 23-25 months is a reasonable timeframe to capture clinically important outcomes. | Clinical review at 24 months (range 23-25 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion with clinical cure (i.e. complete resolution of respiratory symptoms and signs). | Children will have a standardised respiratory clinical assessment, completed by either a member of the study team or health provider. These children will be reviewed at week 4, however many children will reside in geographically isolated locations, thus a range of 4-6 weeks is a reasonable time frame to capture clinically important outcomes. | Clinical review week 4 (range 4-6 weeks) | 
| Time to next respiratory-related hospitalisation assessed by chart reviews | Data will be captured through chart reviews of children's medical records (e.g. hospital and/or community health record) and/or information from parents in next 12 months | Clinical review week 4 (range 4-6 weeks) | 
| Adverse events | Adverse effects will be monitored (anorexia, nausea, vomiting, abdominal pain, diarrhoea, rashes) while children are actively taking trial medication (e.g. 8 days). Parents will also keep a diary of adverse events. | Adverse events monitored while participant taking trial medication | 
| Nasopharyngeal bacteria antibiotic resistance patterns | Nasopharyngeal respiratory antibiotic resistance will be assessed using nasal swabs. Nasopharyngeal respiratory bacterial pathogens and antibiotic resistance will be assessed using research laboratory's previously published methods. | Baseline (admission to hospital, week 4 (range 4-6 weeks) and 12 months (range 12-14 months) | 
| Gene expression data | Gene expression micro-arrays will be performed in a subgroup of children (where bloods can be obtained) | Baseline (hospital admission) and 4-6 weeks (where possible) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Children, Anti-Bacterial Agents, Indigenous Population, Hospitals