Study to Assess Efficacy of Artemether-lumefantrine Prophylaxis Against Forest Malaria in Cambodia (PAL_Cambodia)

University of Oxford

Status: Completed

Conditions: Malaria

Treatments: Drug: Artemether-lumefantrine; Dietary Supplement: Multivitamin

Study type: Interventional

Funder types: Other

Identifiers

NCT04041973

MAL19001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,480 patients

Sex: All

Ages: 16 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria

• Male or female, adults aged between 16 and 65 years.
• 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

• For females: known pregnancy or breast feeding
• 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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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1,480 participants in 2 patient groups

ACT arm

Experimental group

Description:

Artemether-lumefantrine (AL) x 3 days followed by 1 day per week

Treatment:

Drug: Artemether-lumefantrine

Multivitamin arm

Active Comparator group

Description:

Multivitamin x 3 days followed by 1 day per week

Treatment:

Dietary Supplement: Multivitamin