Study to Assess Efficacy of Artemether-lumefantrine Prophylaxis Against Forest Malaria in Cambodia (PAL_Cambodia)
NCT ID: NCT04041973
Last Updated: 2024-03-20
Study Results
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Basic Information
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COMPLETED
NA
1480 participants
INTERVENTIONAL
2020-03-11
2021-03-17
Brief Summary
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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.
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Detailed Description
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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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
SINGLE
Study Groups
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ACT arm
Artemether-lumefantrine (AL) x 3 days followed by 1 day per week
Artemether-lumefantrine
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.
Multivitamin arm
Multivitamin x 3 days followed by 1 day per week
Multivitamin
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.
Interventions
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Artemether-lumefantrine
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.
Multivitamin
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.
Eligibility Criteria
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Inclusion Criteria
* Planning to travel to the forest within the next 72 hours and stay overnight.
* Written informed consent.
* Willingness and ability of the participants to comply with the study protocol for the duration of the study.
Exclusion Criteria
* Participants who have received artemisinin or a derivative or an artemisinin-containing combination therapy (ACT) within the previous 7 days.
* History of allergy or known contraindication to artemisinins, lumefantrine or multivitamins
* Documented or claimed history of cardiac conduction problems
* Severe vomiting or diarrhoea
* Signs/symptoms of clinical malaria (febrile or history of fever in the previous 24 hours) confirmed by RDT.
16 Years
65 Years
ALL
Yes
Sponsors
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Global Fund
OTHER
University of Oxford
OTHER
Responsible Party
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Principal Investigators
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Richard J Maude, M.D.
Role: PRINCIPAL_INVESTIGATOR
Mahidol Oxford Tropical Medicine Research Unit
Locations
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Pursat Referral Hospital/Kravanh Health Center
Pursat, , Cambodia
Stung Treng Referral Hospital/Siem Pang Health Center
Stung Treng, , Cambodia
Countries
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References
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Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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MAL19001
Identifier Type: -
Identifier Source: org_study_id
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