Study to Compare the Triple ACT AL+AQ With the ACT AL in Cambodia and Vietnam
Condition: Malaria, Falciparum
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 3

Summary: 
      This study is a multi-centre, open-label randomised trial to assess the efficacy, safety and
      tolerability of the Triple ACT artemether-lumefantrine+amodiaquine (AL+AQ) compared to the
      ACT artemether-lumefantrine (AL) in uncomplicated falciparum malaria in Cambodia and Vietnam.
      The estimated total sample size is 600 patients from 2 sites in Cambodia and 2 sites in
      Vietnam. There are 2 treatment arms Arm 1: Artemether-lumefantrine for 3 days Arm 2:
      Artemether-lumefantrine for 3 days plus Amodiaquine for 3 days. According to the World Health
      Organization guideline, all patients except children under 10 kilograms will also be treated
      with a single dose of primaquine as a gametocytocidal treatment.

      Funder :Bill & Melinda Gates Foundation (BMGF) Grant reference number: OPP1132628
    

Detailed description: 
      "The study of artemether-lumefantrine or artemether-lumefantrine combined with amodiaquine
      will be a two-arm randomized open label comparative study.

      The main activity proposed is a series of detailed in vivo clinical, parasitological and
      pharmacological assessments in 600 subjects across 2 sites in Cambodian (400 subjects) and 2
      sites in Vietnam (200 subjects). The subjects will be randomized between the ACT
      artemether-lumefantrine and the TACT artemether-lumefantrine+amodiaquine.

      Parasite clearance rates will be assessed by repeated assessments of the parasite counts
      after the start of the antimalarial treatments. Efficacy, safety and tolerability of ACTs and
      TACTs will be assessed through weekly follow up visits where vital signs, symptom
      questionnaires, physical examinations, blood smears, biochemistry assays and full blood
      counts will be performed.

      Ex vivo assessments of parasite susceptibility to artemisinins and partner drugs will be
      measured and compared to historical data, clinical phenotype and other sites in an effort to
      identify artemisinin and partner drug resistance.

      This study will obtain data on the effect of antimalarials on the corrected QT intervals. In
      addition, the effects of antimalarials on factors such as post-treatment haematocrit and
      haemoglobin levels will be assessed. Extensive pharmacokinetic analysis will allow for an
      assessment of drug-drug interactions.

      Plasma histidine-rich protein 2 (HRP2) levels (a marker of parasite biomass) that could
      potentially serve for the estimation of parasitaemia dynamics before and after treatment will
      be measured and subsequently modelled."
    

Intervention name(s): ACT; TACT
Intervention type(s): Drug; Drug
Intervention description(s): Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus low dose primaquine at hour 24; Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus Amodiaquine (150mg) twice daily for 3 days according to weight plus low dose primaquine at hour 24
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: open-label randomised trial
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Malaria, Falciparum; Malaria; Protozoan Infections; Lumefantrine; Artemether; Amodiaquine; Piperaquine; Artemether-lumefantrine combination; Artemisinins; Dihydroartemisinin; Mefloquine; Artemisinin; Antimalarials; Antiparasitic Agents; Anti-Infective Agents; ACT; TACT; Triple ACT(s); Resistance; Antimalarial resistance; Cardiotoxicity; Safety; Tolerability; Efficacy