Hospitalised Pneumonia With Extended Treatment (HOPE) Study

Phase 4

• Conditions: Pneumonia
• Interventions: Drug: Amoxicillin-clavulanic Acid; Drug: Placebo (for Amoxicillin-clavulanic Acid)

• Registration Number: NCT02783859
• Lead Sponsor: Menzies School of Health Research

Brief Summary

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

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

Study Timeline

• Study First Submitted: 2016-05-05
• Study First Submitted QC: 2016-05-23
• Study First Posted: 2016-05-26
• Study Start: 2016-06
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-05
• Last Update Posted: 2022-04-07
• Primary Completion: 2022-06
• Study Completion: 2022-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 314

Inclusion Criteria

1. Hospitalised children aged 3-mo to 5-yrs (in Darwin, children have to be Indigenous)
2. 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
3. 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
4. Have symptoms of no longer than 7 days at point of hospitalisation.

Exclusion Criteria

1. Current wheeze
2. 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
3. Severe malnutrition (weight-for-height Z-score <-3)
4. Complicated (effusion, empyema or abscess) pneumonia, including tuberculosis
5. Extra-pulmonary infection requiring antibiotic therapy (e.g. meningitis)
6. Beta-lactam allergy
7. Previously enrolled
8. Lack a mobile phone and/or unable to return for follow-up clinic visits during the next 24 months

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active arm: Amoxicillin-clavulanic Acid	Amoxicillin-clavulanic Acid	8 days of oral amoxicillin-clavulanic Acid 400/57 duo formulation (70-90mg/kg/day, twice daily dosing: max 980mg per day)
Placebo arm	Placebo (for Amoxicillin-clavulanic Acid)	8 days of oral placebo (equivalent volume as the active arm)

Primary Outcome Measures

Name	Time	Method
The proportion without chronic respiratory symptoms and signs or bronchiectasis.	Clinical review at 24 months (range 23-25 months)	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.

Secondary Outcome Measures

Name	Time	Method
The proportion with clinical cure (i.e. complete resolution of respiratory symptoms and signs).	Clinical review week 4 (range 4-6 weeks)	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.
Gene expression data	Baseline (hospital admission) and 4-6 weeks (where possible)	Gene expression micro-arrays will be performed in a subgroup of children (where bloods can be obtained)
Time to next respiratory-related hospitalisation assessed by chart reviews	Clinical review week 4 (range 4-6 weeks)	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
Adverse events	Adverse events monitored while participant taking trial medication	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.
Nasopharyngeal bacteria antibiotic resistance patterns	Baseline (admission to hospital, week 4 (range 4-6 weeks) and 12 months (range 12-14 months)	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.

Trial Locations

Locations (5)

Sabah Women and Children's Hospital; 🇲🇾 Kota Kinabalu, Sabah, Malaysia

Starship Children's Hospital & KidzFirst Hospital; 🇳🇿 Auckland, New Zealand

University Malaya Medical Centre and Klang Hospital; 🇲🇾 Kuala Lumpur, Malaysia

Menzies School of Health Research; 🇦🇺 Darwin, Northern Territory, Australia

Sarawak General Hospital; 🇲🇾 Sibu, Sarawak, Malaysia