An Open-label Individually Randomised Controlled Trial to Assess the Efficacy of Artemether-lumefantrine Prophylaxis for Malaria Among Forest Goers in Cambodia
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- University of Oxford
- Enrollment
- 1,480
- Locations
- 2
- Primary Endpoint
- Composite endpoint of either clinical malaria with any Plasmodium species within 1-28, 29-56 or 57-84 days, or subclinical infection detected by PCR on days 28, 56 or 84.
Study Overview
Brief 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.
Funder: Wellcome Trust of Great Britain grant number 106698/Z/14/Z and 220211.
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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 16 Years to 65 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
ACT arm
Artemether-lumefantrine (AL) x 3 days followed by 1 day per week
Intervention: Artemether-lumefantrine (Drug)
Multivitamin arm
Multivitamin x 3 days followed by 1 day per week
Intervention: Multivitamin (Dietary Supplement)
Outcomes
Primary Outcomes
Composite endpoint of either clinical malaria with any Plasmodium species within 1-28, 29-56 or 57-84 days, or subclinical infection detected by PCR on days 28, 56 or 84.
Time Frame: 84 days
Secondary Outcomes
- 28-day, 56-day, and 84-day PCR Plasmodium positivity rate for each species(28, 56 and, 84 days)
- Proportion of participants with confirmed malaria reported between day 0 and day 28 for each species(28 days)
- Incidence of confirmed clinical malaria cases as reported to government health facilities and village malaria workers.surveillance data.(1 year)
- Prevalence of Kelch13 mutations and other genetic markers of antimalarial drug resistance of known functional significance.(28 days)
- Incidence of adverse events and serious adverse events by study arms during the course of prophylaxis.(28 days)
- a. Number of people living in each village b. Number of people working in each reported location c. Number of people who have travelled to different locations within the preceding 2 months d. Number of people who have a mobile phone for their own use(28 days)
- Latitude and longitude of the study participant over time in decimal degrees as recorded every 10-30 minutes by a GPS logging device.(28 days)
- Overall prevalence of Plasmodium at baseline, stratified by season and risk factors.(Day 0)
- Day 0, 28, 56 and 84 capillary blood levels of lumefantrine.(84 days)
- Prevalence of serological diagnostic markers of other infectious diseases.(Day 0)