Artemisinin Resistance in Cambodia
Condition: Malaria, Falciparum
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional

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.
    

Detailed description: 
      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.
    

Intervention name(s): Artesunate
Intervention type(s): Drug
Intervention MeSH terms: Artesunate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: artesuante; falciparum malaria; Cambodia; Artemisinin resistance