Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
947
Study information
Scientific title
Efficacy of short course high-dose amoxicillin in the treatment of non-severe community acquired-pneumonia in children: A double-blind, randomised controlled trial
Acronym
HAT
Study hypothesis
We hypothesised that the treatment failure in community acquired non-severe pneumonia (defined by WHO using respiratory rates) or in community acquired non-severe radiological pneumonia (defined by WHO Radiology Working Group) will be lower in children randomised to twice daily three-day oral amoxicillin 90 mg/kg-per-day (high-dose amoxicillin) compared to five-day standard dose co-trimoxazole (standard therapy).
We also hypothesised that carriage of non-susceptible pneumococci to co-trimoxazole will be lower in children treated with high-dose amoxicillin compared to standard therapy.
Ethics approval
The Gambia Government / MRC Laboratories Joint Ethics Committee approved on the 23rd of June 2003
Study design
Two arm randomized double blind single centre clinical trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details below to request a patient information sheet
Condition
Community acquired pneumonia in children
Intervention
Children randomised to high-dose amoxicillin received amoxicillin in 45 mg/kg/dose twice daily (maximum daily dose 2000 mg/day) for three days, followed by placebo twice daily for two days. Children randomised to co-trimoxazole received trimethoprim in 4 mg/kg/dose plus sulphamethoxazole in 20 mg/kg/dose twice daily for 5 days.
Intervention type
Other
Phase
Not Specified
Drug names
Primary outcome measures
1. Treatment failure:
1.1. 3 days after enrolment there was no improvement
or
1.2. within 5 days after enrolment, the study drug was changed to another antibiotic, severe pneumonia or very severe disease develops, or death occurs.
All children were assessed by nurses on days 3 and 5 post-enrolment. Treatment failures were confirmed by study pediatricians.
Secondary outcome measures
1. Relapse:
Reappearance of signs of non-severe pneumonia or appearance of signs of severe pneumonia or very severe disease by day-14 post-enrolment after being declared as cured on day-5 post-enrollment. All children were assessed by nurses on days 5, 14 and 28 post-enrolment for evaluation of clinical outcomes.
2. Compliance:
Proportion of children given full prescribed dosage (this was assessed by measuring left-over trial antimicrobials in the bottles on days 3 and 5).
3. Carriage rate of co-trimoxazole non-susceptible pneumococci on day-28 post-enrollment. Nasopharyngeal swab (NPS) for culture and sensitivity to antimicrobials was collected on days 0 and 28 of enrolment.
Overall trial start date
05/03/2004
Overall trial end date
02/06/2006
Reason abandoned
Eligibility
Participant inclusion criteria
1. Aged 2 to 59 months
2. Either sex
3. Nutritional status: Weight-for-height > 70% of National Center for Health Statistics (NCHS) reference without oedema
4. Non-severe pneumonia according to WHO definition: if the child has fast breathing with cough or difficult breathing and there is no chest indrawing or other danger signs
Participant type
Patient
Age group
Neonate
Gender
Both
Target number of participants
For community acquired pneumonia, the target number of participants was 850 children in each arm. For radiological pneumonia, the target number of participants was 55 children in each arm.
Participant exclusion criteria
1. Having severe pneumonia or very sever disease or if needs oxygen
2. Needed antibiotic, steroid, theophylline or digitalis for treatment of any other condition
3. Had been enrolled in the trial for an earlier episode of pneumonia
4. Was admitted in a hospital in the previous month
5. History of hypersensitivity or intolerance to amoxicillin or co-trimoxazole
6. History of receiving any antibiotic within last 48 hours, this was be confirmed from health cards or village health workers
7. A history of three or more episodes of wheeze, acute bronchial asthma
8. Evidence of underlying haematologic, renal, hepatic or cardiovascular disease
9. Chronic steroid use or concomitant treatment with theophylline or digitalis glycosides
10. Living outside the study area
Recruitment start date
05/03/2004
Recruitment end date
02/06/2006
Locations
Countries of recruitment
Gambia
Trial participating centre
Health Protection Agency Centre for Infections
London
NW9 5EQ
United Kingdom
Funders
Funder type
Research council
Funder name
Medical Research Council Laboratories (Gambia)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary