Study to Assess Efficacy of Artemether-lumefantrine Prophylaxis Against Forest Malaria in Cambodia (PAL_Cambodia)
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional

Summary: 
      In the Greater Mekong Subregion (GMS) adults are at highest risk for malaria. The most
      relevant disease vectors bite during daytime and outdoors which makes forest work a high-risk
      activity for malaria. The absence of effective vector control strategies and limited periods
      of exposure during forest visits suggest that chemoprophylaxis could be an appropriate
      strategy to protect forest workers against malaria.

      The investigators propose the use of Artemether-lumefantrine (AL), a drug whose efficacy
      remains high in the GMS, unlike, for example DHA/piperaquine [20]. The proposed study will
      help to assess the efficacy and feasibility of prophylaxis to prevent malaria in forest
      workers, help to identify the optimal regimen, and predict its efficacy in reducing overall
      transmission. The proposed study is a critical step for future use of chemoprophylaxis to
      protect forest workers in the GMS against malaria.
    

Detailed description: 
      Summary of trial design

      An open-label randomised trial among forest goers comparing the ACT AL with a multivitamin
      with no antimalarial activity to evaluate the efficacy of prophylaxis, and to better
      understand high risk groups and locations of malaria transmission.

      Artemether-lumefantrine prophylaxis trial

      The study of AL versus a multivitamin will be a two-arm randomised open label comparative
      study. Laboratory assessments of malaria infection at baseline and days 28, 56, and 84 will
      be performed blind to treatment allocation and incidence of clinical cases during follow-up
      will be recorded.

      Activities/outcomes

      The main activity proposed is an in vivo clinical assessment of prophylaxis to prevent
      malaria in 4400 participant episodes in 50 villages in Stung Treng and Pursat Provinces,
      Cambodia. The subjects will be randomized in a one-to-one ratio between the ACT AL and a
      multivitamin preparation with no antimalarial activity.

      The study sites have been chosen based on current information on incidence of malaria, known
      predominance of malaria among forest goers, presence of an established clinical research
      programme and feasibility to perform the proposed research activities.

      Efficacy of AL ACT will be assessed through follow up visits every 28 days during a course of
      prophylaxis when temperature, symptom questionnaires, brief physical examinations, and
      malaria parasite PCR, lumefantrine levels, and, in selected individuals, parasite genetics
      will be performed. Episodes of confirmed clinical malaria among study participants at any
      time point between enrolment and follow-up will also be recorded.

      All the organisations in this collaboration will work closely with local counterparts
      including the National Malaria Control Programmes (NMCPs), non-governmental and other
      relevant organisations. Training is an integral part of this collaborative working
      relationship, and the building of local research capacity is an essential component of all
      research plans.

      All research-related activities, from study design, planning, implementation through to
      analysis and writing of reports will be performed jointly with local counterparts. Both
      on-the-job training and formal training will be provided when needed, in particular for Good
      Clinical Practice (GCP) skills.

      The close interaction between WHO and its regional offices will ensure that new knowledge is
      disseminated efficiently and effectively throughout the region.

      Study duration

      The recruitment phase of the study is expected to last 12 months following the intended start
      of recruitment in July 2019. Training and community sensitization will precede study
      execution for 3 months. Data management and analysis, sample analysis (PCR, parasite
      genetics, lumefantrine levels), mathematical modelling and report writing are expected to
      take about 5 months. Therefore, the total time to complete the study will be about 20 months.

      Funder: Global Fund Regional Component of the Regional Artemisinin-resistance Initiative
      (RAI2E) Grant
    

Intervention name(s): Artemether-lumefantrine; Multivitamin
Intervention type(s): Drug; Dietary Supplement
Intervention description(s): One tablet AL contains 20 mg artemether and 120 mg lumefantrine
The prophylaxis will start with a 3-day course of twice daily AL. This will be followed by 2 doses 8 hours apart on one day per week for up to 3 28-35 day consecutive follow-up periods and for 4 weeks after leaving the forest.; One tablet contains Vitamin-A : 5000 USP units, Vitamin D: 400 USP Units, Ascorbic acid: 75 mg, Thiamine Mononitrate: 2 mg, Riboflavin: 3 mg, Niacin amide: 20 mg.
The prophylaxis will start with a 3-day course of twice daily AL. This will be followed by 2 doses 8 hours apart on one day per week for up to 3 28-35 day consecutive follow-up periods and for 4 weeks after leaving the forest.
Intervention MeSH terms: Lumefantrine; Artemether; Artemether, Lumefantrine Drug Combination
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Prevention