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

• Register: ANZCTR
• Last refreshed on: 16 February 2021
• Main ID: ACTRN12616000046404
• Date of registration: 19/01/2016
• Prospective Registration: Yes
• Primary sponsor: Menzies School of Health Research
• Public title: 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
• Scientific title: 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
• Date of first enrolment: 30/05/2016
• Target sample size: 314
• Recruitment status: Active, not recruiting
• URL: https://anzctr.org.au/ACTRN12616000046404.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Blinded (masking used);Assignment: Parallel;Type of endpoint: Safety/efficacy;
• Phase: Phase 4

Countries of recruitment

Australia, Malaysia, New Zealand

Contacts

• Name: Prof Anne Chang

• Name: Dr Gabrielle McCallum

Key inclusion & exclusion criteria

Inclusion criteria: 1) Hospitalised children aged 3-mo to <6-yrs (in Darwin, children have to be Indigenous)
(2) Have features of severe pneumonia on admission (temperature >37.50C or a history of fever at home or observed at the referring clinic, age-adjusted tachypnoea [RR>50 if <12-mo; RR>40 if >12-mo] with chest wall recession and/or SpO2 <92% in air), and consolidation on CXR as diagnosed by treating clinician
(3) After 1-3 days of IV antibiotics, are afebrile, with improved respiratory symptoms and signs, SpO2 >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.
(5) Recruited within 24 hours of admission to ward
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


Age minimum: 3 Months
Age maximum: 6 Years
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Pneumonia in children;
Pneumonia in children

Infection - Studies of infection and infectious agents

Public Health - Other public health

Respiratory - Other respiratory disorders / diseases

Intervention(s)

All participants will have received 24-72 hours of intravenous site specific antibiotics, followed by 3 days of oral amoxicillin-clavunate acid, prescribed by site hospitals. Participants will then receive active or placebo treatment for an additional 8 days as below.

Active arm: 8 days of oral amoxcillin-clavulanate 400/57 duo formulation (70-90mg/kg/day, twice daily dosing; max 980mg per day)

Placebo arm: 8 days of oral placebo (equivalent volume as the active arm)

Treatment dose (range) is determined by local site hospital treatment protocols. Parents will keep a medication diary and/or receive phone calls to monitor adherence to intervention medication. Where possible, we will also collect empty medication bottles at the 4 week clinical review.

Primary Outcome(s)

The proportion without chronic respiratory symptoms and signs or bronchiectasis. We will capture any further chronic respiratory symptoms and signs or bronchiectasis though the child’s medical records (community or hospital) and clinical review[We aim to review these children at 24 months, However, many children will reside in geographically isolated locations, thus a range of 23-26 months is a reasonable time frame to capture clinically important outcomes.]

Secondary Outcome(s)

Adverse events (anorexia, nausea, vomiting, abdominal pain, diarrhoea, rashes) [We will monitor adverse effects while children are actively taking medication. Parents will keep a diary of adverse events. ]

Nasopharyngeal respiratory bacterial pathogens and antibiotic resistance will be assessed using nasal swabs.

This is a composite secondary outcome and can not be separated.[Nasopharyngeal respiratory bacterial pathogens and antibiotic resistance will be assessed using our research laboratory’s previously published methods at baseline (admission to hospital), week 4 (range 4-6 weeks) and 12 months (range 12-14 months).]

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.]

Gene expression of targeted genes. This is a composite outcome, We will perform gene expression studies of the blood using micro-arrays and quantify selected gene targets as determined from the experimental group (a subset of participants where blood was collected)[Baseline (hospital admission) and 4-6 weeks (where possible, i.e. in a subset of children). A blood sample will be taken at baseline and again at week 4-6. At each of these time points, gene expression and target genes will be assessed.]

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 (doctor, research nurse), or community health centre staff member (if required)[We aim to review these children 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.]

Secondary ID(s)

Nil known

Source(s) of Monetary Support

National Health and Medical Research Council

Ethics review

Status: Approved
Approval date: 25/02/2016
Contact:

Human Research Committe of the Northern Territory Department of Health and Menzies School of Health Research

Status: Not approved
Approval date:
Contact:

Medical research and ethics committee (MREC)

Status: Not approved
Approval date:
Contact:

University of Malaya Research Ethics Committee-(UMREC)

Results

• Date Posted: 11/02/2021