Malaria Active Epidemiology and Treatment Study

Study Overview
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Brief Summary
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An observational cohort and malaria treatment study in Cambodia.

Detailed Description
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This is an active observational Cohort Study of malaria epidemiology with a nested two arm, randomized, open label Treatment Study comparing the efficacy, safety, tolerability and pharmacokinetics of a two versus three day course of Dihydroartemisinin-Piperaquine (DP) for those developing uncomplicated malaria. At the conclusion of the Cohort Study, a subset of volunteers with documented exposure to Plasmodium vivax during the study will be treated with primaquine as presumptive anti-relapse therapy directed against the exoerythrocytic malaria stages of P. vivax, and followed passively for an additional 6 months.

Official Title
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An Active Malaria Epidemiology Cohort Study With Evaluation of a 2 Day Versus 3 Day Treatment Regimen of Dihydroartemisinin (DHA)-Piperaquine for Patients With Uncomplicated Malaria

Conditions
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Malaria

Intervention / Treatment
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* Drug: Dihydroartemisinin piperaquine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Otherwise healthy volunteer, 18-65 years of age, eligible for care at an RCAF facility, and at risk for contracting malaria Able to provide informed consent Likely to reside in endemic area for the duration of the study Available for follow-up for anticipated study duration, and agrees to participate for the duration of the study Authorized by local commander to participate in the study if on active duty Exclusion Criteria: History of allergic reaction or contraindication to DHA or piperaquine Significant acute comorbidity requiring urgent medical intervention Pregnant or lactating female, or a female of childbearing age who does not agree to use a highly effective method of birth control during the study Clinically significant abnormal EKG, including a QTc interval > 500 ms. Judged by the investigator to be otherwise unsuitable for study participation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3 day therapy<br>Total dose split over 3 days (3 tablets per day) | Drug: Dihydroartemisinin piperaquine<br>* 40/320 mg tablets, 9 tablets total<br>* Other names: Artekin, Duo-cotexcin;|
| Experimental: 2 day therapy<br>Total dose split over 2 days (4.5 tablets per day) | Drug: Dihydroartemisinin piperaquine<br>* 40/320 mg tablets, 9 tablets total<br>* Other names: Artekin, Duo-cotexcin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adequate clinical and parasitological response to a treatment regimen of DHA-PIP for Plasmodium falciparum | Number of malaria recurrences for 2 and 3 day DHA-PIP drug regimens within 42 days after treatment of malaria infection, diagnosed by positive PCR-corrected malaria microscopy. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Cambodian study subjects with reduced or null activity hepatic cytochrome P450 2D6 alleles | Using Polymerase Chain Reaction-based bead array assays, genotype the human hepatic CYP2D6 allele in study participants giving informed consent for genetic testing | 1 year | 
| Number of subjects with reduced or null hepatic CYP2D6 enzyme phenotype using activity-score A system | For each CYP2D6 genotype determined, use the AS-A system to assign predicted metabolism phenotype | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Plasmodium falciparum, Plasmodium vivax