Ethiopia Malaria Therapeutic Efficacy Study

Sponsor

Centers for Disease Control and Prevention (U.S. Fed)

Overall Status

Completed

CT.gov ID

NCT01052584

Collaborator

United States Agency for International Development (USAID) (U.S. Fed), Columbia University (Other)

354

Enrollment

Locations

Arms

Duration (Months)

177

Patients Per Site

58.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

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.

Condition or Disease	Intervention/Treatment	Phase
Malaria	Drug: Chloroquine- P. vivax Drug: Artemether-Lumefantrine: P. vivax Drug: Artemether-lumefantrine: P. falciparum	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

354 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2009

Actual Primary Completion Date :

Jan 1, 2010

Actual Study Completion Date :

Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Chloroquine-P. vivax P. vivax randomized to receive chloroquine 3-day regimen	Drug: Chloroquine- P. vivax 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)
Experimental: Artemether-Lumefantrine: P. vivax	Drug: Artemether-Lumefantrine: P. vivax 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
Experimental: Artemether-lumefantrine: P. falciparum 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 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

Arm

Intervention/Treatment

Experimental: Chloroquine-P. vivax

P. vivax randomized to receive chloroquine 3-day regimen

Drug: Chloroquine- P. vivax

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)

Experimental: Artemether-Lumefantrine: P. vivax

Drug: Artemether-Lumefantrine: P. vivax

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

Experimental: Artemether-lumefantrine: P. falciparum

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

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.