Official Title: “Chloroquine and Amodiaquine for Treatment of Symptomatic Children With Plasmodium Malaria in Guinea-Bissau”

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 another 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 will be obtained weekly until day 35. In case of a reappearance of parasites the children will be re-treated with sulfadoxine/pyrimethamine.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: May 2004

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 microliters 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.

Intervention(s) in this Clinical Trial

• Drug: chloroquine
• Drug: amodiaquine

Primary Measures

• Parasite reappearance rate
• hospitalization during follow-up

Secondary Measures

• Genetic markers in parasites
• recrudescence rate
• re-infection rate

Inclusion Criteria:

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

Exclusion Criteria:

• Severely 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 idiosyncratic reactions to any of the study drugs

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 15 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Bandim Health Project

Overall Clinical Trial Officials and Contacts

Peter Aaby Study Director Bandim Health Project  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00137514

Study ID Number: PSB-2001-chl-amo

ClinicalTrials.gov Identifier: NCT00137514

Health Authority: Guinea-Bissau: Ministry of Health