Official Title: “Chloroquine and Coartem for Treatment of Symptomatic Children With Plasmodium Falciparum in Guinea Bissau.”

This study will evaluate the efficacy of treatment with artemether-lumefantrine as compared to chloroquine in the dose of 50 mg/kg for treatment of malaria in children in Guinea-Bissau.

The genetic basis of the parasites for developing resistance will be examined. Children coming to one of the Health Centres with symptoms of malaria and a positive malaria test will be included. The children will be followed weekly until day 70. In case of reappearance of parasites the child will be re-treated with the opposite study drug.

Study Type: Interventional

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

Study Primary Completion Date: December 2008

This study compares treatment of uncomplicated malaria in children in Guinea-Bissau with artemether-lumefantrine (Coartem) with that of treatment with chloroquine 50 mg/kg.

Furthermore, the genetic basis of anti-malarial resistance in Guinea-Bissau will be studied by analyzing specific single nucleotide polymorphisms in pfcrt and pfmdr1 in blood samples from this in vivo trial. We also intend to study whether the recent report that chloroquine sensitive parasites are selected at recrudescence after Coartem is confirmed in Bissau.

Following consent to participate, children visiting one of the Health Centres in the study area with mono-infection with Plasmodium falciparum are by block-randomization allocated to one of the treatment groups. The treatment is given supervised by one of the health workers and malaria film taken on day 2 and 3. The children are visited and malaria films obtained once weekly until day 70. On day seven, 100 microliter of capillary blood are drawn for analyses of analyses of drug concentrations in whole blood. On inclusion and whenever a child has recurrent parasitaemia, a filter-paper blood-sample is collected for later PCR analysis.

On the day of inclusion, on day 42 and on day 70 the haemoglobin level is measured.

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 the health centre in case of any illness. Participating children will be examined and treated free of charge. The opposite study drug will be used for re-treatment of children in case of recrudescence, and the child will be followed as previously planned.

The results from this study could be used for the planning of the recommendations for treatment of malaria in Guinea-Bissau. It will provide the National Malaria Programme with information of the efficacy of Coartem before it is implemented.

Intervention(s) in this Clinical Trial

• Drug: Chloroquine
  • Chloroquine tablets gives as 50 mg/kg divided into 6 doses giver twice a day for 3 days.
• Drug: Artemether-lumefantrine (Coartem)
  • Will be dosed according to the recommendations of WHO. Will be given at time: 0 h, 8 h, 24 h, 36 h,48 h and 60 h. The dosage will be according to bodyweight of the child as follows: 5-14 kg: 1 tablet, 15-24 kg: 2 tablets, 25-34 kg: 3 tablets, < 34 kg: 4 tablets.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1 Coartem
  • Treatment of documented malaria in children following the dosages recommended by the manufacturer.
• Active Comparator: 2 Chloroquine
  • The antimalarial actually used in Guinea-Bissau is the dosage of 50 mg/kg given twice a day for 3 days.

Primary Measures

• Parasite reappearance rate,
  • Time Frame: 70 days
    Safety Issue?: No

Secondary Measures

• genetic markers of resistance
  • Time Frame: 70 days
    Safety Issue?: No
• recrudescence and re-infection rates
  • Time Frame: 70 days
    Safety Issue?: No
• Hospitalisation during follow-up
  • Time Frame: 70 days
    Safety Issue?: No
• Haemoglobin changes
  • Time Frame: 70 days
    Safety Issue?: No

Inclusion Criteria:

• Children presenting at one of the health centres in the study area
• Symptoms suggestive of malaria
• At least 20 P.falciparum parasites per 200 leucocytes
• Living in the study area (to enable follow-up)

Exclusion Criteria:

• Danger signs
• By the responsible doctor evaluated to need to be transferred to the national hospital as an in-patient
• Previous idiosyncratic reactions to any of the study drugs

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 6 Months

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  

Overall Contact: Poul-Erik Kofoed, MD, Ph.d +45 76 36 22 30 pekofoed@dadlnet.dk

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00426439

Study ID Number: PSB-2006-Coartem

ClinicalTrials.gov Identifier: NCT00426439

Health Authority: Guinea-Bissau: Ministry of Health