the Tafenoquine Roll-oUt STudy (TRuST)
The Brazilian Ministry of Health (MoH) and MMV, will conduct a study to understand the feasibility of providing appropriate radical cure treatment (primaquine - PQ - or tafenoquine – TQ) based on the results of G6PD testing conducted in real-world settings. This study, known as the Tafenoquine Roll-oUt STudy (TRuST), is being conducted in the municipalities of Manaus, Amazonas (AM), and Porto Velho, Rondônia (RO). The results will provide evidence for the MoH to decide whether to adopt the new tools (semiquantitative G6PD testing and TQ) for use within the health services, and how to best deploy them in P. vivax endemic areas. TRuST has already received ethical approval by CONEP, the National Ethics Committee in Brazil, attesting the study’s reliability and compliance with national research standards.
Besides CONEP’s approval, the Commission of Technology Incorporation in the Public Health System (CONITEC), the Brazilian Health Technology Assessment body, has reviewed the evidence available on the new tools and approved their temporary use in the study’s municipalities. This enabled the National Malaria Control Program (NMCP) to officially recommend the use of TQ and the semiquantitative G6PD test for Manaus (AM) and Porto Velho (RO) during the study duration in addition to PQ.
The new tools will be provided to the health care facilities together with the regular antimalarial drugs chloroquine (CQ) and PQ that are already part of the P. vivax malaria treatment guidelines in Brazil and provided by the MoH. After confirming the diagnosis of P. vivax malaria and measuring the patient’s G6PD enzyme levels, the health care provider will provide the appropriate treatment for relapse prevention (tafenoquine (TQ) or primaquine (PQ)) based on the updated treatment algorithm.
The health care provider will record information about the results of the malaria test and G6PD diagnosis as well as treatment provided, in the Epidemiological Surveillance Information System (SIVEP) – Malaria, following the regular health service routine. Only patients who consent to data sharing will be included in the study database, after being de-identified. The study will start at 10 higher-level facilities and will only be extended to lower-level facilities following an interim analysis and a positive recommendation from the Independent Study Oversight Committee (ISOC).
To issue this recommendation, the ISOC will evaluate the percentage of patients that receive TQ or daily PQ as per protocol, the number and frequency of cases with suspected and confirmed acute hemolytic anemia, health care provider and patient experience with the new clinical management tools and their general acceptability to both groups. It is anticipated that about 16,000 patients will be enrolled in the study during its one-year duration.
Partner organizations are responsible for different aspects of the programme. It is the MoH and the state and municipal health secretariats’ role to deploy the new tools in the health care facilities in Manaus and Porto Velho, through the update of the guidelines and surveillance reporting forms, training of health care workers, supervision, surveillance, supply of G6PD tests and drugs, as well as managing and reporting adverse events. The study team (MMV, Tropical Medicine Foundation (FMT), and the Tropical Medicine Research Centre of Rondônia (CEPEM)), will be responsible for procuring the G6PD tests and TQ, supporting the MoH in developing training and patient information materials, analyzing the routine de-identified surveillance data collected through the health system and developing the study’s reports.