Hospitalised Pneumonia With Extended Treatment (HOPE) Study (HOPE)

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Pneumonia
• Intervention / Treatment: Drug: Amoxicillin-clavulanic Acid; Drug: Placebo (for Amoxicillin-clavulanic Acid)

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 Type: Interventional
• Enrollment (Anticipated): 314
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Northern Territory
    • Darwin, Northern Territory, Australia, 0812
      • Menzies School of Health Research
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • University Malaya Medical Centre and Klang Hospital
  • Sabah
    • Kota Kinabalu, Sabah, Malaysia, 88996
      • Sabah Women and Children's Hospital
  • Sarawak
    • Sibu, Sarawak, Malaysia, 96000
      • Sarawak General Hospital
• New Zealand
  • Auckland, New Zealand, 1142
    • Starship Children's Hospital & KidzFirst Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active arm: 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)	Drug: Amoxicillin-clavulanic Acid
Placebo Comparator: Placebo arm; 8 days of oral placebo (equivalent volume as the active arm)	Drug: Placebo (for Amoxicillin-clavulanic Acid)

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Menzies School of Health Research
• Collaborators: University of Malaya; Nanyang Technological University; Griffith University; The University of Queensland; Queensland University of Technology; Sarawak General Hospital
• Investigators: Principal Investigator: Anne Chang, PhD, Menzies School of Health Research

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: May 5, 2016
• First Submitted That Met QC Criteria: May 23, 2016
• First Posted (Estimate): May 26, 2016

Study Record Updates

• Last Update Posted (Actual): April 7, 2022
• Last Update Submitted That Met QC Criteria: April 5, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Children; Hospitals; Anti-Bacterial Agents; Indigenous Population
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Amoxicillin; Clavulanic Acid; Clavulanic Acids; Amoxicillin-Potassium Clavulanate Combination
• Other Study ID Numbers: HOPE_V5_01022017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No