FocaL Mass Drug Administration for Vivax Malaria Elimination

NCT05690841 | Recruiting Phase 3 DMC

• 3 other identifiers: 22-364171U01AI15796223-0008
• Study Type: interventional
• Target: 7,530
• Locations: 1 country
• Sites: 1

Brief Summary

FLAME is an open-label cluster-randomized controlled trial that aims to determine the effectiveness of focal mass drug administration (fMDA) to reduce the incidence of Plasmodium vivax malaria in the Loreto Department in Peru. Standard interventions, including symptomatic and asymptomatic screening for malaria infections, provision of insecticide-treated bednets, and environmental transmission monitoring, will be compared to clusters of villages randomized to receive anti-malarial drugs.

Conditions

Plasmodium Vivax Malaria; Malaria

Keywords

Antimalarial drugs; Primaquine; Chloroquine; Tafenoquine; Parasitic disease

Outcome Measures

Primary Outcomes (1)

• Cumulative Incidence of Plasmodium vivax infections

  Number of microscopy-confirmed, Plasmodium vivax malaria cases in residents reported from health facilities per population over the 36-month follow-up study period

  From enrollment through study completion, over 36-month follow-up study period

Secondary Outcomes (11)

• Prevalence of Plasmodium vivax infection

  At endline survey in trial year 4, 3 years after enrollment in study in trial year 1

• Plasmodium vivax seroprevalence

  At endline survey in trial year 4, 3 years after enrollment in study in trial year 1

• Genetic diversity of Plasmodium vivax

  From enrollment through study completion, over 4 trial years

• Tolerability of study drugs

  Over drug administration period, unique for each study drug (7 days for CQ/PQ regimens and 3 days for CQ/TQ regimens)

• Adherence to study drugs

  Unique for each patient based on drug regimen (7 days for CQ/PQ regimens and 3 days for CQ/TQ regimens)

Study Arms (2)

Control: Standard Interventions

NO INTERVENTION

Standard interventions for the control cluster will include providing participants with long-lasting insecticide-treated bednets, management of known and possible mosquito breeding sites, passive case detection through detection and diagnosis of symptomatic cases of malaria in health facilities and through community health workers (conducted in villagers with fever), microscopy testing in households of recent index cases to detect asymptomatic malaria cases, and treatment of active cases of malaria (artesunate-mefloquine (AS-MQ) for Plasmodium falciparum and Chloroquine (CQ) (10 mg/kg on days 1 and 2, followed by 5 mg/kg on day 3) + PQ (0.5mg/kg x 7 days).

Focal Mass Drug Administration (fMDA)

EXPERIMENTAL

Standard interventions in addition to focal mass drug administration. Focal mass drug administration will include using primaquine, chloroquine, and tafenoquine, for high-risk individuals residing in households that are within 200 meters of a Plasmodium vivax (Pv) index case households from the prior 2 years (including individuals in the index case household). Pv index cases include symptomatic cases detected at health facilities or in fever screenings, and asymptomatic cases identified during routine active case detection by health facilities. Households will then be notified regarding their potential to receive two rounds fMDA that cycle. Eligibility to receive medications as part of fMDA will be assessed prior to each administration and include glucose 6 phosphate dehydrogenase (G6PD) testing and counseling if not previously conducted or result is not available on the participant's identification card.

Drug: Focal Mass Drug Administration (fMDA)

Interventions

Focal Mass Drug Administration (fMDA) DRUG

Administration of focal mass drug administration for high-risk individuals residing in households that are within 200 meters of a Plasmodium vivax index case households from the prior 2 years (including individuals in the index case household). Intervention to be administered two times, two months apart each cycle, for 3 cycles spaced apart by regular intervals. Each year will include 2 rounds of fMDA. Round 1) Chloroquine (CQ)+ Tafenoquine (TQ) for \>= 16y (CQ: Day1 600 mg, Day 2 600 mg, Day 3 300 mg CQ, TQ 300 mg on Day 1); CQ+ Primaquine (PQ) for \<16y (CQ: age-based dosing, PQ age-based dosing); CQ+PQ for G6PD intermediate individuals \>=6mo and \<16y ((CQ: Day1 600 mg, Day 2 600 mg, Day 3 300 mg, PQ age-based dosing). Round 2) single dose CQ+TQ for \>= 16y (CQ: Day1 600 mg, TQ 300 mg on Day 1); single dose CQ+PQ for \<16y (CQ: age-based dosing, PQ age-based dosing); single dose CQ+PQ for G6PD intermediate individuals \>=6mo and \<16y ((CQ: Day1 600 mg, PQ age-based dosing).

Focal Mass Drug Administration (fMDA)

Eligibility Criteria

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

You may qualify if:

• Cluster eligibility
• Within 8 hours transport of Iquitos
• Incidence \<250/1000 and \>2 cases year prior to trial
• Population size (\<650)
• Chloroquine (CQ) eligibility
• Resides in neighboring household but within 200 m of Pv index case in the past 2 years
• Age ≥6 months old
• Present for intervention
• Adult ≥18 years old that provides informed consent
• A child ≥8 years and \<18 years old that provides informed assent and has informed consent from their parents
• A child ≥6 months old and \<8 years old that has informed consent from their parents
• Tafenoquine (TQ) eligibility
• Eligible to receive CQ
• Age ≥16 years old
• Adult ≥18 years old that provides informed consent

You may not qualify if:

• Chloroquine eligibility
• History of retinal or visual field changes
• Known hypersensitivity or adverse reaction to CQ
• Currently taking CQ or have taken CQ in the past four weeks
• Ineligible for TQ or PQ (see criteria below)
• Hemoglobin \<9 g/dL
• Tafenoquine eligibility
• G6PD deficiency or intermediate status (defined as activity ≤6.0 UI/gHb per SD biosensor)
• G6PD status unknown or refusal of G6PD status test
• Acute or severe malaria
• Pregnancy (known or identified by pregnancy test)
• Refusal of pregnancy test if new amenorrhea in the past 4 weeks
• Woman breastfeeding a child that is G6PD deficient or with unknown G6PD status
• Known hypersensitivity or adverse reaction to TQ or PQ
• Have taken mefloquine (i.e. artesunate- mefloquine), TQ or PQ, or other antimalarial in the past four weeks

Sponsors & Collaborators

• University of California, San Francisco: lead
• Universidad Peruana Cayetano Heredia- subcontractor to UCSF as local Sponsor: collaborator
• PATH: collaborator
• Stanford University: collaborator
• Oxford University Clinical Research Unit Indonesia: collaborator
• Menzies School of Health Research: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Asociación Civil Selva Amazónica

Iquitos, Peru

RECRUITING

Related Publications (8)

• PAHO. Fourth Meeting of the Malaria Technical Advisory Group (TAG) to the Pan American Health Organization (PAHO). Washington D.C.: Pan American Health Organization, World Health Organization, Americas. https://www.paho.org/hq/index.php?option=com_docman&view=download&alias=50391-fourthmalaria-technical-advisory-group-meeting-report-may-washington-dc&category_slug=malariatechnical-advisory-group&Itemid=270&lang=en; 2019.

  BACKGROUND

• Hsiang MS, Ntuku H, Roberts KW, Dufour MK, Whittemore B, Tambo M, McCreesh P, Medzihradsky OF, Prach LM, Siloka G, Siame N, Gueye CS, Schrubbe L, Wu L, Scott V, Tessema S, Greenhouse B, Erlank E, Koekemoer LL, Sturrock HJW, Mwilima A, Katokele S, Uusiku P, Bennett A, Smith JL, Kleinschmidt I, Mumbengegwi D, Gosling R. Effectiveness of reactive focal mass drug administration and reactive focal vector control to reduce malaria transmission in the low malaria-endemic setting of Namibia: a cluster-randomised controlled, open-label, two-by-two factorial design trial. Lancet. 2020 Apr 25;395(10233):1361-1373. doi: 10.1016/S0140-6736(20)30470-0.

  PMID: 32334702 BACKGROUND

• Ntuku H, Smith-Gueye C, Scott V, Njau J, Whittemore B, Zelman B, Tambo M, Prach LM, Wu L, Schrubbe L, Kang Dufour MS, Mwilima A, Uusiku P, Sturrock H, Bennett A, Smith J, Kleinschmidt I, Mumbengegwi D, Gosling R, Hsiang M. Cost and cost effectiveness of reactive case detection (RACD), reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) to reduce malaria in the low endemic setting of Namibia: an analysis alongside a 2x2 factorial design cluster randomised controlled trial. BMJ Open. 2022 Jun 23;12(6):e049050. doi: 10.1136/bmjopen-2021-049050.

  PMID: 35738650 BACKGROUND

• Hsiang MS, Hwang J, Tao AR, Liu Y, Bennett A, Shanks GD, Cao J, Kachur SP, Feachem RG, Gosling RD, Gao Q. Mass drug administration for the control and elimination of Plasmodium vivax malaria: an ecological study from Jiangsu province, China. Malar J. 2013 Nov 1;12:383. doi: 10.1186/1475-2875-12-383.

  PMID: 24175930 BACKGROUND

• Llanos-Cuentas A, Lacerda MVG, Hien TT, Velez ID, Namaik-Larp C, Chu CS, Villegas MF, Val F, Monteiro WM, Brito MAM, Costa MRF, Chuquiyauri R, Casapia M, Nguyen CH, Aruachan S, Papwijitsil R, Nosten FH, Bancone G, Angus B, Duparc S, Craig G, Rousell VM, Jones SW, Hardaker E, Clover DD, Kendall L, Mohamed K, Koh GCKW, Wilches VM, Breton JJ, Green JA. Tafenoquine versus Primaquine to Prevent Relapse of Plasmodium vivax Malaria. N Engl J Med. 2019 Jan 17;380(3):229-241. doi: 10.1056/NEJMoa1802537.

  PMID: 30650326 BACKGROUND

• World Health Organization (WHO). WHO Guidelines for malaria. 3 June 2022. https://reliefweb.int/report/world/who-guidelines-malaria-3-june-2022#:~:text=The%20WHO%20global%20malaria%20strategy,residual%20foci%20of%20malaria%20transmission.

  BACKGROUND

• Fine SR, Soto Calle V, Altamirano Quiroz A, Rodriquez Ferruci H, Manrique P, Wu X, Carrasco Escobar G, Benjamin-Chung J, Bennett A, Auburn S, Price RN, Greenhouse B, Baird JK, Domingo GJ, Roh ME, Rosas A, Llanos-Cuentas A, Hsiang MS. FocaL mass drug administration for Plasmodium vivax malaria elimination (FLAME): study protocol for an open-label cluster randomized controlled trial in Peru. Trials. 2025 Oct 14;26(1):408. doi: 10.1186/s13063-025-09112-1.

  PMID: 41088393 DERIVED

• Fine S, Quiroz AA, Calle VS, Manrique P, Rodriguez H, Carrasco G, Benjamin-Chung J, Bennett A, Auburn S, Price R, Greenhouse B, Baird JK, Domingo G, Roh M, Rosas A, Llanos-Cuentas A, Hsiang M. FocaL mass drug Administration for Plasmodium vivax Malaria Elimination (FLAME): study protocol for an open-label cluster randomized controlled trial in Peru. Res Sq [Preprint]. 2025 Apr 17:rs.3.rs-5594891. doi: 10.21203/rs.3.rs-5594891/v1.

  PMID: 40321759 DERIVED

MeSH Terms

Conditions

Malaria, Vivax; Malaria; Parasitic Diseases

Condition Hierarchy (Ancestors)

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

Study Officials

• Michelle Hsiang, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Alejandro Llanos-Cuentas, MD, PhD

  Universidad Peruana Cayetano Heredia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sydney Fine, MPH

CONTACT

415-476-5494; sydney.fine@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2023
• First Posted: January 19, 2023
• Study Start: October 14, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: November 14, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

PE (1)