This study will evaluate the efficacy of the treatment recommended by the National Malaria Programme in Guinea-Bissau as compared to a higher dose of chloroquine and to an other anti-malarial drug, amodiaquine. The genetic basis of the parasites for developing resistance will be examined. Children coming to Bandim Health Centre with symptoms of malaria and a positive malaria test will be included. The children will be visited and malaria films obtained weekly until day 35. In case of reappearance of parasites the child will be re-treated with sulfadoxine/pyrimethamine.

Condition	Intervention	Phase
Malaria, Falciparum	Drug: Drug: chloroquine and amodiaquine	Phase IV

Further Study Details: 

Primary Outcomes: Parasite reappearance rate; hospitalization during follow-up
Secondary Outcomes: genetic markers in parasites; recrudescense rate; re-infection rate
Expected Total Enrollment:  720

This study compares treatment of uncomplicated malaria in children in Guinea-Bissau as recommended by the national malaria programme (chloroquine in a total dose of 25 mg/kg), either with a total dose of 50 mg/kg chloroquine or with a total dose of 15 or 30 mg of amodiaquine. As both annual in vitro studies (from 1992 to 2004 except 1998, 1999) and several in-vivo studies from Guinea-Bissau indicate a fairly stable chloroquine resistance prevalence, another aim of this study is to evaluate the genetic basis of chloroquine resistance in Guinea-Bissau by analyzing specific single nucleotide polymorphisms in pfcrt and pfmdr1 in blood samples from this in vivo trial.

Following consent to participate, children visiting the Bandim Health Centre on the outskirts of Bissau with mono-infection with Plasmodium falciparum are by block-randomization allocated to one of the four different treatment groups. The treatment is given supervised by one of the health workers. The children are visited and malaria films obtained on day 2 and day 7 and then once weekly until day 35. On day seven, 100 microliter of capillary blood are drawn for analyses of chloroquine or amodiaquine concentrations in whole blood. Whenever a child has recurrent parasitaemia, a filter-paper blood-sample is collected for later PCR analysis.

If parasites reappear in 50% or more of at least 40 children in one of the treatment groups this treatment arm should be terminated. During the study parents are recommended to bring the child to Bandim Health Centre in case of any illness. Participating children will be examined and treated free of charge Following the recommendations of the national Malaria Programme sulfadoxine/pyrimethamine will be used for re-treatment of children in case of recrudescence,

The results from this study could be used when giving the needed new recommendations for treatment of malaria in Guinea-Bissau. If still effective mono-therapy with a higher dose of chloroquine could be used until the introduction of a better treatment is possible. When artemisinine combination therapy is going to be introduced in Guinea-Bissau the results could be helpful in deciding if amodiaquine should be considered as the partner drug – and in which dose.

Ages Eligible for Study:  up to  15 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

Patients < 15 years presenting af Bandim Health Centre symptoms suggestive of malaria at least 20 P.falciparum parasites per 200 leukocytes in a thick film lives in Bandim (to enable follow-up) -

Exclusion Criteria:

Sevelely ill children considered needing the services of a hospital by the medical doctor in charge stated medication with other antimalarials within one week prior to treatment previous idiosyncrastic reactions to any of the study drugs

-

Guinea-Bissau, Bissau
      Bandim Health Project, Apartado 861,  Bissau,  Guinea-Bissau

Study chairs or principal investigators

Peter Aaby,  Study Director,  Bandim Health Project   

Study ID Numbers:  PSB-2001-chl-amo; 2004-126 (SAREC).
Last Updated:  September 12, 2005
Record first received:  August 28, 2005
ClinicalTrials.gov Identifier:  NCT00137514
Health Authority: Guinea-Bissau: Ministry of Health
ClinicalTrials.gov processed this record on 2005-09-13