A Phase 3 interventional study of Focal Mass Drug Administration (fMDA) in Plasmodium Vivax Malaria and Malaria, sponsored by University of California, San Francisco. Recruiting at 1 site in Peru. Per ClinicalTrials.gov, last updated 2026-06-09.
Sponsored by University of California, San Francisco · Phase 3, Interventional, and Prevention
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.
This trial is an open-label cluster-randomized controlled trial in Loreto Region, Peru, a low transmission setting (i.e. anual incidence \<250/1000), where the unit of randomization is a village, or cluster. There will be two study arms: Control and fMDA. Villages will receive fMDA or control based on a restricted randomization that includes baseline factors such as incidence, distance to a health post, and population.
The interventions for both control and fMDA clusters will include standard interventions (high coverage of vector control, passive and active symptomatic case management, and RACD of asymptomatic cases). The intervention will take place in 2 rounds for three cycles, each cycle separated by regular intervals. fMDA will target high-risk villagers (individuals residing in households that are within 200 meters of a Pv index case households from the prior 2 years). High-risk status will be determined in each survey before the administration of Round "a" of fMDA. Pv index cases refers to confirmed Pv cases reported by the health system.
In each cycle of fMDA, the 1st round will include 3 days of chloroquine (CQ) for treatment of Pv asexual blood stages, with TQ for Pv liver stages. With a prolonged half-life up to 15 days and post-treatment effect observed up to 77 days. TQ will also have a prophylactic and likely gametocytocidal effect for Pv and Pf. For continued anti-relapse, prophylactic, and transmission-blocking effects, a follow-up round will include TQ with single-dose CQ (sdCQ). If TQ, but not PQ, is contraindicated, a standard 7-day PQ course will be used. CQ, including in a single dose, will potentiate the anti-relapse effect of PQ, and likely TQ. Preliminary data from the study area shows that 32% of the study population is \<16 years old and will receive PQ. However, the investigators do not anticipate this to influence the impact of the fMDA due to our use of directly observed therapy (DOT). If pediatric TQ is approved for use in Peru during the study, an addendum to the protocol will be presented for approval by the IRB and INS and incorporated into the study.
An endline survey will be carried out at the end of the 3-year trial intervention period. An interim survey will also be conducted in the entirety of the population both arms. In each of these surveys, a dried blood spot will be collected from all participants. Anyone with fever in the prior 48 hours and a positive blood smear from a local health post will receive treatment per national policy. Anyone with fever in the prior 48 hours without a positive blood smear will be encouraged to go to a health post. To maximize public health relevance, the trial will be pragmatic and implemented through the existing health system.
The primary research objectives are:
123 studies on the registry are indexed under Malaria, Vivax; 19 are open to participants now.
This study's planned enrollment of 7,530 is above the median of 150 across 103 interventional studies indexed under Malaria, Vivax.
Browse Malaria, Vivax studies →University of California, San Francisco is the lead sponsor of 2,169 studies on the registry; 372 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Cluster eligibility
Chloroquine (CQ) eligibility
Tafenoquine (TQ) eligibility
Primaquine eligibility
Baseline evaluation and informed consent
-Villagers will be eligible to participate in surveys if they slept in a household in cluster randomized to control or focal mass drug administration (fMDA) for at least one night in the past four weeks
Eligibility for fMDA
Exclusion Criteria:
Chloroquine eligibility
Tafenoquine eligibility
Primaquine eligibility
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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).
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)
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).
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
Time frame: From enrollment through study completion, over 36-month follow-up study period
Prevalence of Plasmodium vivax infection
Proportion of individuals with polymerase chain reaction (PCR)-confirmed infection in an endline survey
Time frame: At endline survey in trial year 4, 3 years after enrollment in study in trial year 1
Plasmodium vivax seroprevalence
Proportion of participants who are seropositive, rate at which seronegative individuals became seropositive estimated from age-specific seroprevalence from endline survey, adjusted by modeling longitudinal individual serological status and/or antibody titers
Time frame: At endline survey in trial year 4, 3 years after enrollment in study in trial year 1
Genetic diversity of Plasmodium vivax
Diversity of locally acquired infections as defined by sequencing results
Time frame: From enrollment through study completion, over 4 trial years
Tolerability of study drugs
Vomiting following administration of study drugs and non-adherence related to adverse effects
Time frame: 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
Number of missed doses
Time frame: Unique for each patient based on drug regimen (7 days for CQ/PQ regimens and 3 days for CQ/TQ regimens)
Refusal rates
Number of refusals divided by number of individuals invited to participate
Time frame: During each fMDA round, twice per year for 3 consecutive years
Program costs per unit fMDA round
Total costs divided by number of fMDA rounds
Time frame: From enrollment through study completion, over 4 years
Program costs per unit
Total costs divided by number of individuals receiving intervention
Time frame: From enrollment through study completion, over 4 years
Cost per incident case averted
Difference in cost between fMDA and control divided by the difference in the effect (incidence)
Time frame: From enrollment through study completion, over 4 years
Cost per disability life year (DALY)
Difference in cost between fMDA and control divided by the difference in the effect (DALYs)
Time frame: From enrollment through study completion, over 4 years
Cost per economic dollar due to malaria saved
Difference in cost between fMDA and control divided by the difference in the effect (economic dollar due to malaria)
Time frame: From enrollment through study completion, over 4 years
Plan to share: No — After completion of the trial, un-blinding will be performed and results will be disseminated widely at scientific meetings and in publications in peer-reviewed journals. Upon publication of the trial results, data will be made available for to other individuals in the scientific community upon request. Informed consent documents for the study will include a specific statement relating to posting and sharing of study information and that no individual identities will ever be used in these materials and forums. Human genomic data will consist of G6PD and CYP2D6 single nucleotide polymorphisms (SNPs). Plasmodium parasite genomic data will consist of microhaplotype SNPs. All genomic data will be shared in accordance with institutional and NIH policies. Informed consent forms will indicate that the investigators may share genetic data and no individual identities will be linked to these data. All genetic information generated will be analyzed through pipelines in Git.
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