Journal Article

FocaL mass drug administration for Plasmodium vivax malaria elimination (FLAME): study protocol for an open-label cluster randomized controlled trial in Peru

Roh, Michelle E., Carrasco Escobar, Gabriel, Benjamin-Chung, Jade, Bennett, Adam, Soto Calle, Veronica, Manrique, Paulo, Greenhouse, Bryan, Llanos-Cuentas, Alejandro, Auburn, Sarah, Baird, J. Kevin, Price, Ric N., Hsiang, Michelle S., Fine, Sydney R., Rodriquez Ferruci, Hugo, Wu, Xue, Altamirano Quiroz, Astrid, Domingo, Gonzalo J., Rosas, Angel

2025

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Aminoquinolines / Antimalarials / Antimalarials - administration & dosage / Antimalarials - adverse effects / Antimalarials - economics / Biomedicine / Case management / Chloroquine - administration & dosage / Chloroquine - adverse effects / Chloroquine - economics / Cost analysis / Disease Eradication - methods / Distribution / Drug therapy / Drug Therapy, Combination / Health facilities / Health Sciences / Humans / Infection control / Infections / Malaria / Malaria, Vivax - diagnosis / Malaria, Vivax - drug therapy / Malaria, Vivax - parasitology / Malaria, Vivax - prevention & control / Mass Drug Administration / Medicine / Medicine & Public Health / Methods / Microscopy / Peru - epidemiology / Plasmodium vivax - drug effects / Plasmodium vivax - pathogenicity / Prevention / Primaquine - administration & dosage / Primaquine - adverse effects / Randomized Controlled Trials as Topic / Serology / Statistics for Life Sciences / Study Protocol / Time Factors / Treatment Outcome