FocaL Mass Drug Administration for Vivax Malaria Elimination — FLAME  

Malaria Clinical Trial

Official title: FocaL Mass Drug Administration for Vivax Malaria Elimination (FLAME): a Pragmatic Cluster Randomized Controlled Trial in Peru

Status Not yet recruiting

Clinical Trial 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.

Clinical Trial Description

This trial 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 two months apart for three cycles, each cycle separated by regular intervals of 9-11 months. 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 (2 months after each 1st 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 end-line survey will be carried out at the end of the 3-year trial intervention period. Interim surveys will also be conducted in both arms. In each of these surveys, a blood sample will be collected in microtainer tubes, and a dried blood spot will be collected from anyone with fever in the prior 48 hours and a positive blood smear from a local health post. They 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, but if not, study staff will collect a blood smear and they will receive treatment per national policy if found to have malaria. To maximize public health relevance, the trial will be pragmatic and implemented through the existing health system.

The primary research objectives are:

1. To determine the effectiveness of three rounds of fMDA to reduce Pv transmission in the Loreto Department, Peru compared to standard interventions.

2. To evaluate the safety and tolerability of fMDA by measuring incidence of severe adverse events or severe malaria in the treatment arm.

3. To measure the cost-effectiveness and acceptability of fMDA by calculating the cost per malaria case averted for intervention and control arms. ;

Related Conditions & MeSH terms

• Malaria
• Malaria, Vivax

• NCT number: NCT05690841
• Study type: Interventional
• Source: University of California, San Francisco
• Contact: Sydney Fine, MPH
• Phone: 415-476-5494
• Email: sydney.fine@ucsf.edu
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 1, 2024
• Completion date: May 1, 2027