Kilimanjaro IPTi Drug Options Trial
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:
- 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.
- Determination of whether a short acting antimalarial drug (Lapdap) is as effective as a long acting drug (mefloquine) when used for IPTi.
- Investigation of the effect of the intensity of transmission on the requirements for a long or short acting drug for IPTi.
- 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.
Drug: IPTi mefloquine
Drug: Chlorproguanil dapsone
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
|Official Title:||Drug Options for Intermittent Preventive Treatment for Malaria in Infants in an Area With High Resistance to Sulfadoxine/Pyrimethamine: an Evaluation of Short and Long-Acting Antimalarial Drugs|
- 1. Incidence of clinical malaria: [(history of fever during previous 2 days or axillary temperature >37.5ºC) + parasitaemia of any density + absence of any other obvious causes of fever] during the period of 3-11 months of age [ Time Frame: 3-11 months of age ] [ Designated as safety issue: No ]
- 1.Mean Hb at 10-12 months of age (one month after the third course of IPTi) [ Time Frame: 10-12 months of age ] [ Designated as safety issue: No ]
- 2.Incidence of severe anaemia (Hb <7 g/dl) during the period of 3-11 months of age [ Time Frame: 3-11 months of age ] [ Designated as safety issue: No ]
- 3.Prevalence of parasitaemia at 10-12 months of age (one month after the third course of IPTi) [ Time Frame: 10-12 months of age ] [ Designated as safety issue: No ]
- 4.Incidence of clinical malaria [as defined above] during the period of 12-23 months of age. [ Time Frame: 12-23 months of age ] [ Designated as safety issue: No ]
- 5.Level and repertoires of plasma antibodies to Plasmodium falciparum variant surface antigen (anti-VSA antibodies) at 10 and 18 months of age. [ Time Frame: 10 and 18 months of age ] [ Designated as safety issue: No ]
|Study Start Date:||January 2005|
|Study Completion Date:||June 2008|
|Primary Completion Date:||April 2008 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
Other Name: FansidarDrug: Sulphadoxine-pryrimethamine
IPTi doses 1 and 2, at ages 2 and 3 months, sulphadoxine 250mg, pyrimethamine 12.5mg IPTi doses 3, at 9 months of age, sulphadoxine 500mg, pyrimethamine 25mg
Other Name: Fansidar
Other Name: LariumDrug: IPTi mefloquine
IPTi doses 1 & 2 at ages 2 & 3 months, mefloquine 125mg IPTi dose 3 at 9 months, mefloquine 250mg
Other Name: Larium
|Experimental: Chlorproguanil dapsone||
Other Name: LapdapDrug: Chlorproguanil dapsone
IPTi doses 1 and 2 at ages 2 and 3 months, doses 15mg chlorproguanil and 18.75mg dapsone IPTi dose 3 at 9 months of age, doses 22.5mg chlorproguanil and 28.13mg dapsone
Other Name: Lapdap
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|Ministry of Health, Korogwe and Same District MCH clinics|
|Tanga, Tanga and Kilimanjaro, Tanzania|
|Study Director:||Roly Gosling, MBChB, MRCP||London School of Hygiene and Tropical Medicine|
|Principal Investigator:||Daniel Chandramohan, MBBS,PhD||London School of Hygiene and Tropical Medicine|
|Principal Investigator:||Brian Greenwood, FRCP, FRS||London School of Hygiene and Tropical Medicine|