Artemisinin Resistance in Bangladesh
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Artemisinin Resistance in Bangladesh|
- Cure [ Time Frame: 42 days ] [ Designated as safety issue: No ]Cure is defined as adequate clinical and parasitological response (ACPR) as opposed to early treatment failure / late treatment failure
- Treatment response [ Time Frame: 42 Days ] [ Designated as safety issue: No ]Treatment response parameters: parasite, fever, and gametocyte clearance
|Study Start Date:||June 2008|
|Study Completion Date:||November 2009|
|Primary Completion Date:||November 2009 (Final data collection date for primary outcome measure)|
Experimental: AS 2mg/kg
Artesunate monotherapy 2mg/kg/day for 7 days
2 or 4 mg/kg/day for 7 days
Experimental: AS 4mg/kg
Artesunate monotherapy 4mg/kg/day for 7 days
2 or 4 mg/kg/day for 7 days
Active Comparator: QD Control
Quinine-doxycycline for 7 days
quinine-doxycycline for 7 days
A total number of 100 volunteers with acute uncomplicated falciparum malaria will be randomly assigned one of 3 arms to be treated with artesunate monotherapy or quinine/doxycycline for 7 days at a ratio of 2:2:1. 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 aged 8 to 65 years with uncomplicated falciparum malaria recruited at the Bandarban Sadar Hospital, Bangladesh.
The artesunate will be administered orally (a single dose of 2 or 4 mg/kg/day) over a total duration of 7 days by directly observed therapy.
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 later. Thereafter they will be followed as outpatients until Day 42 with scheduled follow-up visits on Day 14, 28, 35, and 42.
In vitro drug sensitivity assays will be performed from samples on inclusion and in case of recrudescence. Drug levels will be measured on the first and last day of therapy.
Primary clinical outcome is cure (Adequate Clinical and Parasitological Response - ACPR) on Day 28 and 42. 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 for patients in whom recrudescences cannot be fully excluded. 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 twice daily until parasite clearance and on Days 7, 14, 21, 28, 35, and 42 or whenever symptoms consistent with malaria appear. Plasma samples for determining drug levels will be obtained on the first and last day of therapy. Study participation for each individual will be 42 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00639873
|Bandarban Sadar Hospital|
|Bandarban Sadar, Bandarban, Bangladesh|
|Principal Investigator:||Harald Noedl, MD, PhD||Medical University of Vienna|