The Tafenoquine Roll-out STudy (TRuST)
The Tafenoquine Roll-oUt Study (TRuST) was the first real-world, observational study to assess the feasibility of providing appropriate relapse-prevention treatment with tafenoquine (TQ) or primaquine (PQ) based on G6PD test results. The study, co-sponsored by the Brazilian Ministry of Health (MoH) and MMV, was conducted in the municipalities of Manaus, Amazonas (AM), and Porto Velho, Rondônia (RO) and was launched in September 2021. TRuST was led by two malaria researchers and their associated institutes in Brazil: Dr. Marcus Lacerda from Dr. Heitor Vieira Dourado Tropical Medicine Foundation (FMT-HVD) and Dr. Dhelio Pereira, Tropical Medicine Research Centre of Rondônia (CEPEM).
The study assessed the feasibility of introducing a new P. vivax treatment protocol with point-of-care G6PD testing and single-dose tafenoquine. The new tools were provided to the health care facilities together with the regular blood-stage antimalarial drug, chloroquine (CQ). After confirming the diagnosis of P. vivax malaria and measuring the patient’s G6PD enzyme levels, the health care provider provided the appropriate treatment for relapse prevention (TQ or PQ) based on the updated treatment algorithm.
The health care provider recorded information about the results of the malaria test and G6PD diagnosis as well as the treatment provided in the Epidemiological Surveillance Information System (SIVEP) – Malaria, following the regular health service routine. Only patients who provided informed consent to data sharing have been included in the study database, after being de-identified.
The study was implemented in two phases by the MoH and the State and Municipal health secretariats in Manaus and Porto Velho. The first phase started in September 2021 and was conducted in nine high- and medium-level health facilities. In February 2022, the study was expanded to 40 lower-level facilities in the same municipalities following the recommendation by the Independent Study Oversight Committee based on the review of the first interim analysis. The last patient was recruited in the study on 31st August 2022. A qualitative research study known as ‘Quali-TRuST’ was conducted by researchers at FMT-HVD alongside TRuST to understand the perspectives of health workers and patients on the introduction and use of the new tools.
Learn more about the phases of the TRuST study in this infographic.
In December 2022, the results of the first and second interim analysis of TRuST were included in a comprehensive dossier, along with the results from QualiTRuST, a cost-effectiveness and a budget impact analysis and other tafenoquine and G6PD related scientific evidence, that was submitted to the National Commission for the Incorporation of Technologies (CONITEC) in the national health system (SUS) requesting the incorporation of single-dose TQ and the STANDARD™ G6PD test into the SUS. In June 2023, CONITEC decided in favor of the incorporation, making Brazil the first country to incorporate single-dose TQ for the treatment of P. vivax malaria.
Key results: New tools can be appropriately incorporated within the health services
The primary objective of TRuST was to investigate whether patients with P. vivax aged ≥16 years were treated with tafenoquine according to the appropriate level of G6PD enzyme activity. Scientific papers are still going through a review process by journals, but some of the key conclusions are highlighted below.
TRuST and Quali-TRuST Key conclusions
- The level of compliance with the new treatment protocol of providing tafenoquine based on appropriate levels of G6PD activity was above 99% and was consistent across higher/medium- and lower-level healthcare facilities.
- The healthcare providers were able to routinely test patients for G6PD activity before providing radical cure with tafenoquine or primaquine.
- Routine testing for G6PD activity before providing radical cure was feasible at different levels of the Brazilian health system.
- Healthcare providers and patients reported the use of a single dose for radical cure as a positive development, contributing to improving malaria treatment.
- Patients with previous infections of P. vivax highlighted the benefit of the reduced pill count and shorter treatment.
- As with any new intervention, there was a steep learning curve for healthcare providers to incorporate G6PD testing in health units' routine. The challenges at the beginning with using the G6PD test were overcome with training and practice.
- Brazil’s health surveillance system is very robust and enables the linkage of surveillance, hospitalization, and mortality data to monitor adverse events related to antimalarials.
- These results suggest that the training provided for health workers on the use of tafenoquine was appropriate. Training was delivered by the State and Municipal Health secretariats and the study team, focusing on how to use the G6PD test and provide the appropriate treatment based on the MoH guidelines.