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

NCT04041973 | Completed

• 1 other identifier: MAL19001
• Study Type: interventional
• Target: 1,480
• Locations: 1 country
• Sites: 2

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.

Conditions

Malaria

Outcome Measures

Primary Outcomes (1)

• 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.

  84 days

Secondary Outcomes (10)

• 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

Study Arms (2)

ACT arm

EXPERIMENTAL

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

Drug: Artemether-lumefantrine

Multivitamin arm

ACTIVE COMPARATOR

Multivitamin x 3 days followed by 1 day per week

Dietary Supplement: Multivitamin

Interventions

Artemether-lumefantrine DRUG

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.

ACT arm

Multivitamin DIETARY_SUPPLEMENT

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.

Multivitamin arm

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Oxford: lead
• Global Fund: collaborator

Study Sites (2)

Pursat Referral Hospital/Kravanh Health Center

Pursat, Cambodia

Location

Stung Treng Referral Hospital/Siem Pang Health Center

Stung Treng, Cambodia

Location

Related Publications (25)

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  BACKGROUND

• Tripura R, von Seidlein L, Sovannaroth S, Peto TJ, Callery JJ, Sokha M, Ean M, Heng C, Conradis-Jansen F, Madmanee W, Peerawaranun P, Waithira N, Khonputsa P, Jongdeepaisal M, Pongsoipetch K, Chotthanawathit P, Soviet U, Pell C, Duanguppama J, Rekol H, Tarning J, Imwong M, Mukaka M, White NJ, Dondorp AM, Maude RJ. Antimalarial chemoprophylaxis for forest goers in southeast Asia: an open-label, individually randomised controlled trial. Lancet Infect Dis. 2023 Jan;23(1):81-90. doi: 10.1016/S1473-3099(22)00492-3. Epub 2022 Sep 26.

  PMID: 36174595 DERIVED

• Maude RJ, Tripura R, Ean M, Sokha M, Peto TJ, Callery JJ, Imwong M, Vongpromek R, Tarning J, Mukaka M, Waithira N, Soviet O, von Seidlein L, Sovannaroth S. Study protocol: an open-label individually randomised controlled trial to assess the efficacy of artemether-lumefantrine prophylaxis for malaria among forest goers in Cambodia. BMJ Open. 2021 Jul 7;11(7):e045900. doi: 10.1136/bmjopen-2020-045900.

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MeSH Terms

Conditions

Malaria

Interventions

Artemether, Lumefantrine Drug Combination; Geritol

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Richard J Maude, M.D.

  Mahidol Oxford Tropical Medicine Research Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2019
• First Posted: August 1, 2019
• Study Start: March 11, 2020
• Primary Completion: March 17, 2021
• Study Completion: March 17, 2021
• Last Updated: March 20, 2024

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share

Locations

CA (2)