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Trial registered on ANZCTR


Registration number
ACTRN12612000994886
Ethics application status
Approved
Date submitted
7/09/2012
Date registered
17/09/2012
Date last updated
17/09/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
Treatment of World Health Organization (WHO) defined non-severe pneumonia in developing countries with three days or five days of oral cotrimoxazole
Scientific title
In children under five with WHO defined non-severe pneumonia, is three days of oral cotrimoxazole have the same efficacy than five days of oral cotrimoxazole in reducing fast breathing?
Secondary ID [1] 281185 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-severe Pneumonia 287361 0
Condition category
Condition code
Infection 287691 287691 0 0
Other infectious diseases
Respiratory 287700 287700 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patient received two bottles, one with a green label contained cotrimoxazole, to be used during the first 3 days, and the second with a red label containing placebo, was used for the subsequent 2 days. Cotrimoxazole (40 mg trimethroprim + 200 mg sulphamethoxazole per 5 ml) was given in a dose of 4 mg/kg twice daily and prepared by SK&F Inc. in Bangladesh and Roche Inc. in Indonesia. The green-labels had six cells to be marked by the caretaker for the 6 doses in the first 3 days and the red label had 4 cells to be marked for the next 2 days. A marked measuring cup was used to help dispense the dose.
The first dose of cotrimoxazole was given by the caretaker under supervision at the health facility, with instructions given for the next doses, home care, follow-up visits and recognition of symptoms associated with very severe pneumonia. In Indonesia the second bottle was given to the caretaker on day 3 at a home visit, whereas in Bangladesh both bottles were given to the caretaker at enrollment. All of the treatments were consumed orally.
Intervention code [1] 285645 0
Treatment: Drugs
Comparator / control treatment
Patient received two bottles, one with a green label contained cotrimoxazole, to be used during the first 3 days, and the second with a red label containing Cotrimoxazole, was used for the subsequent 2 days. Cotrimoxazole (40 mg trimethroprim + 200 mg sulphamethoxazole per 5 ml) was given in a dose of 4 mg/kg twice daily. The green-labels had six cells to be marked by the caretaker for the 6 doses in the first 3 days and the red label had 4 cells to be marked for the next 2 days. A marked measuring cup was used to help dispense the dose.
The first dose of cotrimoxazole was given by the caretaker under supervision at the health facility, with instructions given for the next doses, home care, follow-up visits and recognition of symptoms associated with very severe pneumonia. In Indonesia the second bottle was given to the caretaker on day 3 at a home visit, whereas in Bangladesh both bottles were given to the caretaker at enrollment. All of the treatments were consumed orally.
Control group
Dose comparison

Outcomes
Primary outcome [1] 287940 0
Clinical outcomes on fast breathing. The infants and children were followed up 5 days after enrollment when caretakers were asked about the clinical condition and subjects were assessed clinically for fast breathing. To evaluate fast breathing, the mean of two respiratory rates counted for 1 minute each within 5 minutes was used for all children, when the child was quiet, feeding, or asleep. Children who failed therapy were referred to the hospital for management. Study staff followed children at home if they did not come for follow-up.
Timepoint [1] 287940 0
Five days
Secondary outcome [1] 299084 0
Relapse. On Day 15, we conducted a full clinical assessment, assessed for relapse. A relapse was defined as the appearance of any signs of pneumonia after at least 3 days of being free of symptoms from the original episode.
Timepoint [1] 299084 0
Fifteen days

Eligibility
Key inclusion criteria
The inclusion criteria were: children aged 2-59 months with WHO defined non-severe pneumonia
Minimum age
2 Months
Maximum age
59 Months
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- children with WHO defined severe or very severe pneumonia or any other severe disease
- children with a history of an allergic reaction to cotrimoxazole or three or more episodes of wheeze or current diagnosis of acute asthma
- those who had been enrolled earlier in the study; required antibiotics for any other condition; had been hospitalized in the previous 2 weeks or who had severe malnutrition.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Enrolled children were randomized to receive either 3 or 5 days of oral cotrimoxazole, prepared by SK&F Inc. in Bangladesh and Roche Inc. in Indonesia. A sequence number with random allocation was generated by computer in central office of each site. Each container bottle was numbered based on the randomization, therefore the person who enrolled, give the bottle to the subjects, and performed the follow up were blinded from the type of treatment. This randomization was performed by an individual unrelated to the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomization was done in blocks of 4, 6 and 8, embedded in larger blocks of 24 at each site. The randomization code prepared by computer, by an individual unrelated to the study was kept locked at ICDDR, Dhaka and The Health Research Unit Padjadjaran University, Bandung. Unblinding was done at an investigator’s workshop after completion of the analysis.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
5/07/2001
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
2000
Accrual to date
Final
Recruitment outside Australia
Country [1] 4537 0
Bangladesh
State/province [1] 4537 0
Dhaka
Country [2] 4538 0
Indonesia
State/province [2] 4538 0
West Java

Funding & Sponsors
Funding source category [1] 285960 0
Other
Name [1] 285960 0
Department of Child and Adolescent Health and Development World Health Organization
Country [1] 285960 0
Switzerland
Primary sponsor type
University
Name
The University of Colorado at Denver and The Children’s Hospital
Address
13123 East 16th Avenue
Aurora, CO 80045
Country
United States of America
Secondary sponsor category [1] 284784 0
Other
Name [1] 284784 0
Department of Child and Adolescent Health and Development World Health Organization
Address [1] 284784 0
20 Avenue Appia, Geneva 27, CH1211
Country [1] 284784 0
Switzerland

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287994 0
Ethical Committee Faculty of Medicine Universitas Padjadjaran Hasan Sadikin General Hospital
Ethics committee address [1] 287994 0
Jl. Pasteur No 38, Bandung 40160, West Java Province
Ethics committee country [1] 287994 0
Indonesia
Date submitted for ethics approval [1] 287994 0
Approval date [1] 287994 0
20/05/2001
Ethics approval number [1] 287994 0

Summary
Brief summary
We conducted a trial to compare equivalence of 3 and 5 days of oral cotrimoxazole for treating WHO defined non-severe pneumonia and to study its effect on antimicrobial resistance development in nasopharyngeal Haemophilus influenzae and Streptococcus pneumoniae. The primary hypothesis was that a 3 day course was equivalent to the standard 5 day course of oral cotrimoxazole for the treatment of WHO defined non-severe pneumonia in children aged 2 – 59 months. The secondary hypotheses we tested were a) the relapse rate at 15 days did not differ between the two treatment groups and b) the longer course of antibiotic therapy led to an increased prevalence of S. pneumoniae and H. influenzae resistant to cotrimoxazole. The primary outcome was treatment failure at day 5 and the secondary outcome was relapse at day 15.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34682 0
Address 34682 0
Country 34682 0
Phone 34682 0
Fax 34682 0
Email 34682 0
Contact person for public queries
Name 17929 0
CISSY B. KARTASASMITA
Address 17929 0
Jalan Pasteur 38, Bandung 40160
Country 17929 0
Indonesia
Phone 17929 0
+62 22 2035957
Fax 17929 0
+62 22 2035957
Email 17929 0
[email protected]
Contact person for scientific queries
Name 8857 0
ERIC A.F. SIMOES
Address 8857 0
13123 East 16th Avenue
Aurora, CO 80045
Country 8857 0
United States of America
Phone 8857 0
+ 1 720-777-6977
Fax 8857 0
+ 1 720-777-7295
Email 8857 0
[email protected]

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What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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