FocaL mass drug administration for Plasmodium vivax malaria elimination (FLAME): study protocol for an open-label cluster randomized controlled trial in Peru
Issued Date
2025-10-14
Resource Type
eISSN
17456215
Scopus ID
2-s2.0-105018654977
Pubmed ID
41088393
Journal Title
Trials
Volume
26
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Trials Vol.26 No.1 (2025) , 408
Suggested Citation
Fine S.R., Soto Calle V., Altamirano Quiroz A., Rodriquez Ferruci H., Manrique P., Wu X., Carrasco Escobar G., Benjamin-Chung J., Bennett A., Auburn S., Price R.N., Greenhouse B., Baird J.K., Domingo G.J., Roh M.E., Rosas A., Llanos-Cuentas A., Hsiang M.S. FocaL mass drug administration for Plasmodium vivax malaria elimination (FLAME): study protocol for an open-label cluster randomized controlled trial in Peru. Trials Vol.26 No.1 (2025) , 408. doi:10.1186/s13063-025-09112-1 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/112696
Title
FocaL mass drug administration for Plasmodium vivax malaria elimination (FLAME): study protocol for an open-label cluster randomized controlled trial in Peru
Author's Affiliation
Stanford University
University of California, San Francisco
Harvard T.H. Chan School of Public Health
Universitas Indonesia
Nuffield Department of Medicine
Menzies School of Health Research
Mahidol Oxford Tropical Medicine Research Unit
PATH Seattle
Universidad Peruana Cayetano Heredia, Instituto de Medicina Tropical Alexander von Humboldt
University of California, San Francisco
Harvard T.H. Chan School of Public Health
Universitas Indonesia
Nuffield Department of Medicine
Menzies School of Health Research
Mahidol Oxford Tropical Medicine Research Unit
PATH Seattle
Universidad Peruana Cayetano Heredia, Instituto de Medicina Tropical Alexander von Humboldt
Corresponding Author(s)
Other Contributor(s)
Abstract
BACKGROUND: Outside of sub-Saharan Africa, Plasmodium vivax has become the dominant species of malaria. Focal mass drug administration (fMDA) is a potential strategy to support elimination efforts, but controlled studies are lacking. METHODS: The FocaL mass drug Administration for Plasmodium vivax Malaria Elimination (FLAME) study is a 3-year cluster randomized controlled trial to determine the impact and safety of fMDA to reduce P. vivax transmission. The study will be conducted in Loreto, Peru, where standard interventions have reduced P. vivax cases, but transmission persists due to a high proportion of subclinical infections. Thirty low transmission communities (API < 250 cases/1000 population) will be randomized 1:1 to fMDA versus control using a restricted randomization. All communities will receive Peruvian national standard malaria control measures. In the intervention arm, high-risk individuals (living within 200 m of a P. vivax case reported in the prior 2 years) without contraindication to study medications, including G6PD deficiency, will receive three cycles of fMDA over a 2-year period. Each cycle will include two rounds of directly observed therapy delivered 2 months apart. The fMDA regimen will include 25 mg/kg chloroquine (CQ) plus a single 300 mg dose of tafenoquine (TQ) for individuals age ≥ 16 years, and 25 mg/kg of CQ plus 7 days of 0.5 mg/kg/day of primaquine (PQ) if younger. The primary outcome is the cumulative incidence of symptomatic P. vivax malaria. The sample size provides 80% power to detect at least a 68% relative reduction in cumulative P. vivax incidence, based on alpha of 0.05 and a coefficient of variation (k) of 0.87. Secondary outcomes include safety, cost-effectiveness, and infection prevalence and seroprevalence which will be assessed in annual cross-sectional surveys. Safety will be assessed in passive and active pharmacovigilance, including post-treatment screening for G6PD-associated hemolysis by assessing for anemia and hematuria in a sample. DISCUSSION: The trial will generate evidence regarding fMDA for P. vivax and inform malaria elimination efforts in Peru and similarly endemic settings. Findings will be disseminated in peer-reviewed publications and through stakeholder meetings in Peruvian and international research forums. TRIAL REGISTRATION: Clinicaltrials.gov NCT05690841. This trial was registered on 09 January 2023. Peruvian Clinical Trial Registry (REPEC) 020-23. This trial was registered on 21 February 2024.