Artemisinin Resistance in Cambodia
|First Received Date ICMJE||May 25, 2007|
|Last Updated Date||April 29, 2008|
|Start Date ICMJE||October 2006|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Primary clinical outcome is cure (Adequate Clinical and Parasitological Response - ACPR as defined by WHO criteria) on Day 28.|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT00479206 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Secondary outcome measures are time until parasite, fever, and gametocyte clearance (PCT, FCT, and GCT).|
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Artemisinin Resistance in Cambodia|
|Official Title ICMJE||Artemisinin Resistance in Cambodia|
|Brief Summary||The principal aim of this project is to investigate reports of developing artemisinin resistance in Cambodia using an integrated in vivo - in vitro approach to examine recent alarming reports of treatment failures with advanced combination therapies along the Thai-Cambodian border, which could have major impact on the malaria situation in the affected areas as well as the rest of the malaria-endemic world.|
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.
|Study Type ICMJE||Interventional|
|Study Phase||Not Provided|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Condition ICMJE||Malaria, Falciparum|
|Intervention ICMJE||Drug: Artesunate|
|Study Arms||Not Provided|
|Publications *||Noedl H, Se Y, Sriwichai S, Schaecher K, Teja-Isavadharm P, Smith B, Rutvisuttinunt W, Bethell D, Surasri S, Fukuda MM, Socheat D, Chan Thap L. Artemisinin resistance in Cambodia: a clinical trial designed to address an emerging problem in Southeast Asia. Clin Infect Dis. 2010 Dec 1;51(11):e82-9. doi: 10.1086/657120. Epub 2010 Oct 28.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Enrollment ICMJE||Not Provided|
|Completion Date||February 2007|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years to 65 Years (Adult)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Cambodia|
|Removed Location Countries|
|NCT Number ICMJE||NCT00479206|
|Other Study ID Numbers ICMJE||WRAIR #1296
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||Medical University of Vienna|
|Information Provided By||Medical University of Vienna|
|Verification Date||April 2008|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP