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| Sponsor: | University of Oxford |
|---|---|
| Collaborator: |
Kenya Medical Research Institute |
| Information provided by: | University of Oxford |
| ClinicalTrials.gov Identifier: | NCT00934492 |
Purpose
This trial aims to test the hypothesis that mortality among Kenyan children with severe malnutrition following initial stabilisation is due to ongoing vulnerability to infectious disease, and that co-trimoxazole prophylaxis will reduce mortality.
The objective is to conduct a randomized, double blind, placebo-controlled trial of cotrimoxazole prophylaxis for 6 months among HIV-uninfected children with severe malnutrition following stabilization. The primary outcome will be survival at one year. Secondary outcomes are toxicity, survival at two years, growth, hospitalisation and microbial resistance and ecology.
Cotrimoxazole has striking protective efficacy against mortality among children with HIV, despite not altering the underlying immune deficiency. It is hypothesised that co-trimoxazole prophylaxis will have a similar effect in children immunocompromised because of severe malnutrition. Worldwide, severe malnutrition is commoner than HIV in childhood and co-trimoxazole is cheap and widely available, making it easily translatable to policy.
| Condition | Intervention | Phase |
|---|---|---|
|
Nutrition Disorders Life-Threatening Infection |
Drug: Cotrimoxazole dispersible tablet Drug: Placebo dispersible tablet |
Phase III |
| Study Type: | Interventional |
| Study Design: | Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Efficacy Study |
| Official Title: | Randomized, Placebo Controlled Trial of Cotrimoxazole Prophylaxis Amongst HIV-Uninfected Children With Severe Malnutrition |
| Estimated Enrollment: | 1600 |
| Study Start Date: | August 2009 |
| Estimated Study Completion Date: | August 2013 |
| Estimated Primary Completion Date: | August 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Cotrimoxazole dispersible tablet: Active Comparator
Children between 2-6 months will receive single dispersible tablet of 120mg,daily while children over 6 months to 5 years will receive 240 mg dispersible tablet daily for six months.
|
Drug: Cotrimoxazole dispersible tablet
Cotrimoxazole dispersible tablets 120/240mg daily for six consecutive months.
|
|
Placebo dispersible tablet: Placebo Comparator
Children between 2-6 months will receive single dispersible Placebo tablet of 120mg,daily while children over 6 months to 5 years will receive 240 mg dispersible Placebo tablet daily for six months.
|
Drug: Placebo dispersible tablet
Placebo dispersible tablets 120/240mg daily for six consecutive months.
|
Malnutrition is the most important underlying risk factor for childhood death in developing countries. Severely malnourished children are at greatly increased risk of death from infectious diseases in the community, in hospital and following discharge. Malnutrition and infection are synergistic, in part because malnutrition causes secondary immune deficiency, whilst infections cause losses and diversion of nutrients. This synergy is exacerbated by a high level of exposure to pathogens. Among children treated for severe malnutrition in Africa, mortality following discharge from hospitals ranges between 8% and 41%.
Cotrimoxazole is a synthetic antibacterial combination that blocks two steps of folate metabolism involved in the biosynthesis of nucleic acids and proteins essential to many bacteria and some parasites, including Plasmodium falciparum. It is cheap, widely available and has an established safety profile in African populations. Cotrimoxazole prophylaxis dramatically reduces mortality among children with HIV, irrespective of the degree of immune suppression. The primary effect is in reducing bacterial infection, especially pneumonia. the effect has been demonstrated in areas with high levels of cotrimoxazole resistance bacteria. It is also widely used in developed countries among children with other immune deficiencies to prevent infection. Children with severe malnutrition are immune deficient, as evidenced by their susceptibility to infectious diseases, and may therefore benefit from daily antimicrobial prophylaxis.
The objective is to conduct a randomized, double blind, placebo-controlled trial of co-trimoxazole prophylaxis for 6 months among HIV-uninfected children with severe malnutrition following stabilization. The primary outcome will be survival at one year. Secondary outcomes are toxicity, survival at two years, growth, hospitalisation and microbial resistance and ecology.
Eligibility| Ages Eligible for Study: | 2 Months to 5 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contacts and Locations| Contact: James Berkley | +254 041 7522535/7522063 ext 624 | jberkley@kilifi.kemri-wellcome.org |
| Contact: Johnstone N Thitiri, RN | 041 7522535/7522063 ext 629 | jthitiri@kilifi.kemri-wellcome.org |
| Kenya, Coast | |
| KEMRI/Wellcome Trust Research Programme | |
| Kilifi, Coast, Kenya, 80108 | |
| Principal Investigator: | James A Berkley, MD | Universitiy of Oxford & Kenya Medical Research Institute |
More Information
| Responsible Party: | KEMRI/Wellcome Trust Reaesrch Programme ( Dr. James A Berkley ) |
| Study ID Numbers: | SSC 1562, OXTREC 18 09, WT 083579 |
| Study First Received: | July 7, 2009 |
| Last Updated: | July 7, 2009 |
| ClinicalTrials.gov Identifier: | NCT00934492 History of Changes |
| Health Authority: | Kenya: Ethical Review Committee |
|
Malnutrition Wasting Kwashiorkor Immune deficiency |
Infection Prophylaxis Mortality Kenya |
|
Antimalarials Anti-Infective Agents Communicable Diseases Antiparasitic Agents Antiprotozoal Agents Therapeutic Uses |
Nutrition Disorders Anti-Infective Agents, Urinary Trimethoprim-Sulfamethoxazole Combination Renal Agents Infection Pharmacologic Actions |
