Tolerability and Efficacy of CD+A Compared to AQ+SP for the Treatment of P.Falciparum Malaria in Rwandan Children

Study Overview
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Brief Summary
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In 2005-2006, a clinical trial was carried out to test safety, tolerability and efficacy of the combination chlorproguanil-dapsone+artesunate (CD+A): 800 children aged 12-59 months with uncomplicated P. falciparum malaria randomly allocated to AQ+SP or CD+A were followed up until day 28 after treatment. Adverse events, clinical and parasitological outcomes were recorded.

Detailed Description
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Between 2001 and 2006, as an interim strategy, Rwanda chose amodiaquine+ sulfadoxine-pyrimethamine (AQ+SP) as the first line anti-malaria treatment. Although the clinical response to this combination was relatively good in 2001, since then its efficacy has steadily declined: in 2002 the proportion of successful treatment (recorded at 28 days and PCR-unadjusted) was 83 % (Rwagacondo et al., 2003) and in 2003 it was 74% (Karema et al., 2006). Different artemisinin-based combination treatments (ACTs) such as amodiaquine+artesunate (AQ+AS), dihydroartemisinin-piperaquine (DHAPPQ) and artemether-lumefantrine (ALN) have been tested in the past few years as possible alternatives to AQ+SP (Fanello et al., 2006; Karema et al., 2006). Chlorproguanil-dapsone (also known asLapDap) is an antifolate combination similar to sulfadoxine/pyrimethamine (SP) but for two important features: (1) it is rapidly eliminated and therefore exerts less selective pressure for resistance-conferring parasite mutations than does SP (Winstanley et al., 1997; Nzila et al., 2000b) and (2) it is active against the SP-resistant forms of the parasite that are found in Africa (Mutabingwa et al., 2001a,b; Kublin et al., 2002). Moreover, a pediatric course of treatment of LapDap is estimated to cost $0.15 (Mutabingwa et al., 2001b), making it orders of magnitude less expensive than any marketed antimalarial drug other than chloroquine and SP. In 2005-2006, a clinical trial was carried out to test safety, tolerability and efficacy of the combination chlorproguanil-dapsone+artesunate (CD+A): 800 children aged 12-59 months with uncomplicated P. falciparum malaria randomly allocated to AQ+SP or CD+A were followed up until day 28 after treatment. Adverse events, clinical and parasitological outcomes were recorded. Based on the results of all trials carried out by the NMCP, The Rwandan Ministry of Health has now changed the first line to artemether-lumefantrine (ALN), Coartem®. The drug arrived in the country in October 2006.

Official Title
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Open Study on the Tolerability and Efficacy of the Combination Chlorproguanil-Dapsone+Artesunate Compared to Amodiaquine+Sulfadoxine-Pyrimethamine for the Treatment of Uncomplicated Falciparum Malaria in Rwandan Children

Conditions
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Malaria

Intervention / Treatment
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* Drug: Chlorproguanil-dapsone + artesunate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 12-59 months; Weight ≥5 kg; Monoinfection with P. falciparum; Parasite density between 2,000-200,000/µL; Fever (axillary body temperature =>37.5C) or history of fever in the preceding 24 hours; Packed Cell Volume (PCV) >21%. Exclusion Criteria: Severe malaria; Mixed malaria infection; Any other concomitant illness or underlying disease; Known allergy to the study drugs being used in this trial; Clear history of adequate antimalarial treatment in the previous 72 hours.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 59 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Chlorproguanil-dapsone + artesunate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of microscopically and genotypically confirmed recrudescent infections in the different treatment groups by day 28 |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parasite clearance |  |  | 
| Fever clearance |  |  | 
| Occurrence of adverse events |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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P.falciparum, malaria, lapdap+artesunate, safety, efficay