Chloroquine and Coartem for Treatment of Symptomatic Children With Plasmodium Falciparum in Guinea Bissau

Sponsor

Bandim Health Project (Other)

Overall Status

Completed

CT.gov ID

NCT00426439

Collaborator

(none)

300

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Malaria, Falciparum	Drug: Chloroquine Drug: Artemether-lumefantrine (Coartem)	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Chloroquine and Coartem for Treatment of Symptomatic Children With Plasmodium Falciparum in Guinea Bissau.

Study Start Date :

Dec 1, 2006

Actual Primary Completion Date :

Nov 1, 2008

Actual Study Completion Date :

Nov 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Coartem Treatment of documented malaria in children following the dosages recommended by the manufacturer.	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. Other Names: Brand name: Coartem.
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.	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. Other Names: Brand name: Coartem.

Arm

Intervention/Treatment

Experimental: 1 Coartem

Treatment of documented malaria in children following the dosages recommended by the manufacturer.

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.

Other Names:

Brand name: Coartem.

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.

Drug: Chloroquine

Chloroquine tablets gives as 50 mg/kg divided into 6 doses giver twice a day for 3 days.

Drug: Artemether-lumefantrine (Coartem)

Other Names:

Brand name: Coartem.

Outcome Measures

Primary Outcome Measures

Parasite reappearance rate, [70 days]

Secondary Outcome Measures

genetic markers of resistance [70 days]
recrudescence and re-infection rates [70 days]
Hospitalisation during follow-up [70 days]
Haemoglobin changes [70 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months to 15 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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