Last Updated: 29/10/2025

ACT vs CQ With Tafenoquine for P. Vivax Mono-infection (ACTQ)

Objectives

The study aims to find out whether 450 mg dose of tafenoquine can be combined effectively with Artemisinin Combination Therapy (ACT) providing a short course treatment for P. vivax malaria.

Primary objective: determine whether ACTs (artemether-lumefantrine or dihydroartemisinin-piperaquine (DHA-PPQ)) plus tafenoquine (TQ) is non-inferior to chloroquine (CQ) plus TQ.

Secondary objectives:

Characterise the safety and tolerability of three regimens.
Characterise population pharmacokinetics of tafenoquine in three treatments.
Characterise methaemoglobin levels as in vivo pharmacodynamic proxy of oxidative antimalarial activity of tafenoquine.

Principal Institution

Shoklo Malaria Research Unit (SMRU), Thailand

Principal Investigators / Focal Persons

Aung Pyae Phyo

Partner Institutions

Mahidol Oxford Tropical Medicine Research Unit (MORU), Thailand
University of Oxford, United Kingdom

Rationale and Abstract

In this area of Greater Mekong Subregion (GMS), vivax malaria is the most common kind of malaria. It can stay very long in the liver, and come out later to make another episode of illness. This can happen many times even without a mosquito bite. Only 8-aminoquinoline drugs can kill the liver forms of the malaria parasite. One of these drugs is called primaquine, and it has been used all over the world for a long time. There is now a new formulation of this 8-aminoquinoline drug called tafenoquine that can also treat the malaria in the liver. The main benefit of this drug is that it is a single dose, which makes much convenient for the patients as well as for the malaria control program than conventional 14 days of primaquine. Recent research suggests that ACT (Artemisinin Combination Therapy) may antagonise the efficacy of tafenoquine (Baird et al. 2020 ASTMH Annual Meeting). This could prevent the use of tafenoquine in areas with chloroquine resistant P. vivax parasites where national malaria programmes recommend ACTs for vivax malaria. Also, currently recommended tafenoquine dose is sub-optimal: 300 mg dose proved significantly inferior to low dose primaquine in a meta-analysis of the phase 3 studies when restricted to the Southeast Asian region (Llanos-Cuentas et al. 2019 NEJM; Watson et al. 2022a Elife). A tafenoquine dose of 450mg is predicted to provide >90% of the maximal effect. The objective of this research is to find out whether 450 mg dose of tafenoquine can be combined effectively with ACT providing a short course treatment for P. vivax malaria.

Study Design

ClinicalTrials.gov ID: NCT05788094

Study Type: Interventional

Study Phase: Phase 4

Study Design:

Allocation: Randomized

Interventional Model: Parallel Assignment

Interventional Model Description: Randomised open label non-inferiority trial

Masking: None (Open Label)

Primary Purpose: Treatment

External reference

Project Details Clinical Trials - Project details