Kilimanjaro IPTi Drug Options Trial

• Status: Completed
• Trial end date: 2008-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Malaria and anaemia are major causes of morbidity and mortality in children in sub-Saharan Africa. Administration of three courses of sulfadoxine/pyrimethamine (SP) as intermittent preventive treatment (IPTi) to infants when they receive EPI vaccines reduced the incidence of malaria and anaemia in infants in an area with low SP resistance, low transmission pressure and high bednet use. However, it is not clear whether this observation can be generalised to areas with high transmission and high SP resistance. The mechanism of the protective effect of IPTi is unclear. There is an urgent need to identify other anti-malarial drugs that could be used for IPTi instead of SP.

This study objectives are:

1. Identification of a drug that could be used safely and effectively for IPTi instead of SP in areas, such as north eastern Tanzania, where there is a high level of resistance to SP and amodiaquine.

2. Determination of whether a short acting antimalarial drug (Lapdap) is as effective as a long acting drug (mefloquine) when used for IPTi.

3. Investigation of the effect of the intensity of transmission on the requirements for a long or short acting drug for IPTi.

4. Assessment of the effect of IPTi on the development of clinical immunity in children in low and high transmission areas.

A randomised trial with four treatment regimes is proposed which will be conducted in two different transmission settings. The four treatment regimens are as follows: (1) placebo; (2) mefloquine; (3) Lapdap; (4) SP. All medications will be given at the time of immunisation with DPT/polio 2, DPT/polio 3, and measles vaccines. The study will involve 1280 infants in a high endemic area and 2440 infants in a low endemic area, in Tanzania.The primary outcome is the incidence of clinical malaria.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Gates Malaria Partnership; London School of Hygiene and Tropical Medicine
• Collaborators: Kilimanjaro Christian Medical Centre, Tanzania; National Institute for Medical Research, Tanzania; University of Copenhagen
• Treatments: Chlorproguanil; Dapsone; Fanasil, pyrimethamine drug combination; Mefloquine; Proguanil; Pyrimethamine; Sulfadoxine

Criteria

Inclusion Criteria:

• All infants attending EPI clinics at the 12 study health facilities for first vaccinations. Infants who live within the catchment area of the study health facility and are less than 3 months of age at the time of DPT and Polio 1 vaccination will be eligible for inclusion in the study.

Exclusion Criteria:

• Infants having any of the following conditions will be excluded: (1) history of allergy to study drugs; (2) history of convulsions; (3) clinical features of severe malnutrition or chronic illness including infants with signs of AIDS [HIV prevalence in women of reproductive age in the study area was 11.5% in 1999]39 (4) plans to leave the study area before 12 months of age.(5) weighs <4.5 kgs (6) caretaker declines to give consent.