Ethiopia Malaria Therapeutic Efficacy Study

Study Overview
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Brief Summary
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In this stdy, patients aged above 6 months with symptomatic malaria presenting to health centers will be enrolled for treatment with artemether-lumefantrine for P. falciparum infection, and either artemether-lumefantrine or chloroquine for P. vivax infection. Clinical, parasitologic, and hematologic parameters will be monitored for P. falciparum and P. vivax infection over a 42-day follow-up period, which will be used to evaluate drug efficacy. Results from this research study will be used to assist Ethiopia in assessing their current national malaria drug policies.

Detailed Description
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Following the rapid development of significant drug resistance of Plasmodium falciparum (Pf) to chloroquine and then sulfadoxine-pyrimethamine (the first line therapy in Ethiopia 1998-2004), artemether- lumefantrine (Coartem or AL) was adopted as first line therapy in Ethiopia in 2004. According to the current national malaria diagnosis and treatment guidelines, first-line treatment for uncomplicated falciparum infection is AL. First-line treatment for Plasmodium vivax (Pv) is with chloroquine (CQ) alone without primaquine therapy in malarious areas. For all clinical infection without laboratory confirmation, AL which is effective against both Pf and Pv is the first-line treatment. Thus, in Ethiopia, where treatment for malaria without laboratory confirmation occurs frequently, Pv is often treated with AL as the standard of care. Furthermore, World Health Organization (WHO) recommends AL for the treatment of Pv, where AL has been adopted as first-line treatment for Pf. Now with wide-spread use of AL and CQ, we propose to conduct an antimalarial efficacy study to monitor the effectiveness of these therapies in Ethiopia and to determine how efficacious these drugs remain. This information will inform future policy changes with respect to appropriate antimalarial strategies. The simplest and most universally accepted measure of testing for antimalarial drug treatment efficacy, the standardized procedures outlined in the World Health Organization Assessment and monitoring of antimalarial drug efficacy for the treatment of uncomplicated falciparum malaria and the WHO Monitoring antimalarial drug resistance, will be followed.

Official Title
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Ethiopia In-vivo Efficacy Study 2009: Evaluating the Efficacy of Artemether-lumefantrine for the Treatment of Uncomplicated Plasmodium Falciparum Infection and Either Artemether-lumefantrine or Chloroquine for P. Vivax Infection

Conditions
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Malaria

Intervention / Treatment
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* Drug: Chloroquine- P. vivax
* Drug: Artemether-Lumefantrine: P. vivax
* Drug: Artemether-lumefantrine: P. falciparum


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Slide-confirmed infection with P. falciparum, with parasitemia of 1,000-100,000 asexual forms/ μl or slide confirmed infection with P. vivax with > 250 asexual forms/ μl Lives within 20 km of the enrolling health facility Weight ≥ 5.0 kg Axillary temperature ≥ 37.5º C or history of fever during the previous 24 or 48 hours for P. falciparum and P. vivax infection, respectively Patient or caregiver agrees to all blood draws and return visits. Exclusion Criteria: General danger signs or symptoms of severe malaria Signs or symptoms of severe malnutrition, defined as weight-for-age ≤ 3 standard deviations below the mean (NCHS/WHO normalized reference values; Slide confirmed infection with any other Plasmodium spp. besides falciparum/vivax or mixed plasmodium infection Severe anemia, defined as Hg < 5 g/dl Known hypersensitivity to any of the drugs being evaluated Presence of febrile conditions caused by diseases other than malaria Serious or chronic medical condition (cardiac, renal, hepatic diseases, sickle cell disease, HIV/AIDS) Pregnant or breastfeeding women. Children weighing less than 5 kilograms.

Ages Eligible for Study
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Minimum Age: 6 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chloroquine-P. vivax<br>P. vivax randomized to receive chloroquine 3-day regimen | Drug: Chloroquine- P. vivax<br>* Total of 25mg base per kg over 3 days (10 mg base/kg on Days 1 and 2, and 5 mg base/kg on Day 3)<br>|
| Experimental: Artemether-Lumefantrine: P. vivax<br> | Drug: Artemether-Lumefantrine: P. vivax<br>* administered twice daily for three days as tablets containing 20 mg of artemether plus 120 mg of lumefantrine in a fixed dose combination at a dosage<br>|
| Experimental: Artemether-lumefantrine: P. falciparum<br>administered twice daily for three days as tablets containing 20 mg of artemether plus 120 mg of lumefantrine in a fixed dose combination at a dosage | Drug: Artemether-lumefantrine: P. falciparum<br>* administered twice daily for three days as tablets containing 20 mg of artemether plus 120 mg of lumefantrine in a fixed dose combination at a dosage<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine Early Treatment Failures, Late Clinical Failures, Late Parasitological Failures, or Adequate Clinical and Parasitological Response during 28 days of follow-up for P. falciparum. Measure the treatment failure of AL and CQ for P. vivax |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine Early Treatment Failures, Late Clinical Failures, Late Parasitological Failures, or Adequate Clinical and Parasitological Response during 42 days of follow-up for P. falciparum. Measure the treatment failure of AL and CQ for P. vivax durin |  | 42 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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malaria, therapeutic efficacy, in vivo, artemether lumefantrine, coartem, chloroquine, Plasmodium falciparum, Plasmodium vivax