Artemisinin Resistance in Cambodia
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Artemisinin Resistance in Cambodia|
- Primary clinical outcome is cure (Adequate Clinical and Parasitological Response - ACPR as defined by WHO criteria) on Day 28.
- Secondary outcome measures are time until parasite, fever, and gametocyte clearance (PCT, FCT, and GCT).
|Study Start Date:||October 2006|
|Study Completion Date:||February 2007|
A total number of 90 volunteers with acute uncomplicated falciparum malaria will be randomly assigned to be treated with either artesunate monotherapy for 7 days or the combination of quinine and tetracycline over 7 days (following the 2nd line national treatment guideline of the national malaria control program) at a ratio of 2:1. The study design will be based on the WHO recommendations for the 'Assessment and Monitoring of Antimalarial Drug Efficacy for the Treatment of Uncomplicated Falciparum Malaria' (WHO, 2003). Study participants will be otherwise healthy malaria patients (adult men and non-pregnant women aged 18 to 65 years) with uncomplicated falciparum malaria recruited in Battambong Province, Cambodia.
The artesunate will be administered orally (a single dose of 200 mg per day) over a total duration of 7 days (Directly Observed Therapy). Quinine (30 mg/kg/day) plus tetracycline (25 mg/kg/day) will also be administered over 7 days in split dose every 8 hours following the national treatment guidelines of Cambodia.
Patients will be admitted to the hospital for the duration of study drug administration or until all signs and symptoms of malaria have disappeared, whichever comes first. Thereafter until Day 21 patients have to remain in a malaria-free environment (such as Sampov Luon or Ta Sanh) either in the hospital or in a living facility provided at the study site where the patients will be supervised by study personnel. After Day 21 they will be followed as outpatients until Day 28 with a scheduled follow-up visit on Day 28.
In vitro drug sensitivity assays will be performed from samples on inclusion and in case of recrudescence. Drug levels will be measured in the artesunate arm on the first and last day of therapy.
Primary clinical outcome is cure (Adequate Clinical and Parasitological Response - ACPR) on Day 28. Secondary outcome measures are time until parasite, fever, and gametocyte clearance (PCT, FCT, and GCT). Parasite genotyping will be used to distinguish recrudescences from reinfections by PCR. Subjects will be monitored for clinical adverse events throughout the study duration.
Blood will be drawn on the day of admission (before initiating therapy) for in vitro drug sensitivity testing and for PCR (markers of drug resistance and to distinguish recrudescence from reinfection by genotyping). Malaria smears will be prepared up to 4 times a day until parasite clearance and on Days 7, 14, 21, and 28 or whenever symptoms consistent with malaria appear. Plasma samples for determining drug levels will be obtained on the first and last day of therapy. Over the entire study, up to approximately 64 ml of blood may be drawn by venipuncture. Study participation for each individual will be 28 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00479206
|Tasanh Health Center|
|Tasanh, Batambang, Cambodia|
|Study Director:||Harald Noedl, MD, MCTM, PhD||USAMC-AFRIMS|