Trial reportThe Lancet. Infectious diseases2026
Effectiveness and safety of 7-day high-dose primaquine and single-dose tafenoquine versus 14-day low-dose primaquine in patients with Plasmodium vivax malaria (EFFORT): a multicentre, open-label, randomised, controlled, superiority trial.
Trial report in The Lancet. Infectious diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04411836 (Effectiveness of Novel Approaches to Radical Cure With Tafenoquine and Primaquine - a Randomized Controlled Trial in P. Vivax Patients), which is not on this map. Cited by 12 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Effectiveness of Novel Approaches to Radical Cure With Tafenoquine and Primaquine - a Randomized Controlled Trial in P. Vivax Patients
Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Analysis of the effect of primaquine dose on efficacy, safety, and tolerability in patients with Plasmodium vivax malaria in Ethiopia: a systematic review and individual patient data meta-analysis.Malaria journal · 2026Pooled it
- Dissemination of trial results to study participants in Cambodia, Ethiopia and Pakistan: a qualitative study.BMJ open · 2026Trial
- A systematic review and individual patient data meta-analysis to determine the effect of primaquine dose on efficacy, tolerability and safety in uncomplicatedLancet regional health. Americas · 2026Article
- Seven-day versus fourteen-day low-dose primaquine forThe Lancet regional health. Southeast Asia · 2026Article
- Genetic Evidence of Cross-Border Plasmodium vivax Spread in a Malaria Pre-elimination Region of South Asia.The Journal of infectious diseases · 2026Article
- Community perceptions, trust, and experiences of malaria clinical research and participation in rural Cambodia.Tropical medicine and health · 2026Article
- Building the toolkit to address malaria resurgence and radical cure of vivax malaria in Ethiopia: a meeting report.Malaria journal · 2026Article
- Effect of higher dose primaquine for the radical cure ofThe Lancet regional health. Western Pacific · 2026Article
- Risk perceptions of high-dose primaquine and tafenoquine amongBMJ global health · 2026Article
- High-dose, short-course primaquine after point-of-care G6PD testing for the radical cure ofThe Lancet regional health. Western Pacific · 2026Article
- Dissemination of EFFORT trial results in Indonesia: a stakeholder meeting report on tafenoquine and primaquine for radical cure of Plasmodium vivax.Malaria journal · 2026Article
- G6PD deficiency in Indonesia: a systematic review and update of prevalence and variant maps in the context of malaria elimination.The Lancet regional health. Western Pacific · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
63 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundShorter courses of primaquine and single-dose tafenoquine have potential to improve the prevention of recurrent Plasmodium vivax infections, but there are few data on their comparative effectiveness when provided unsupervised. We aimed to assess the effectiveness and safety of these new treatment options.
methodsWe conducted a multicentre, open-label, randomised, controlled, superiority trial in Ethiopia, Pakistan, Indonesia, and Cambodia. Adult patients (aged ≥18 years, or aged ≥16 years in Indonesia) with uncomplicated P vivax infection and glucose-6-phosphate dehydrogenase (G6PD) activity of 70% or greater were eligible for enrolment. Patients were treated with blood schizonticidal drugs (chloroquine in Ethiopia and Pakistan, dihydroartemisinin-piperaquine in Indonesia, and artesunate-pyronaridine in Cambodia) and randomly assigned (1:1:1) by an independent statistician using randomly permuted blocks of varying sizes to receive 7 days of unsupervised high-dose primaquine (total dose 7 mg/kg), single-dose tafenoquine (300 mg), or 14 days of low-dose primaquine (total dose 3·5 mg/kg). Randomisation was stratified by site. The primary endpoint, assessed in the modified intention-to-treat population (ie, patients who received allocated treatment, and were not lost to follow-up before day 15), was the cumulative incidence of any P vivax parasitaemia within 6 months compared between the primaquine groups, with the comparison of cumulative incidence between the tafenoquine group and the 14-day low-dose primaquine group a secondary endpoint. Key safety outcomes included the numbers of adverse and serious adverse events, including the number of gastrointestinal symptoms as well as the risk of anaemia. Safety outcomes were assessed in all patients who received any doses of study drug. The study is registered at ClinicalTrials.gov, NCT04411836, and is complete.
findingsBetween April 25, 2021 and Sept 13, 2024, 4850 patients were screened for eligibility, of whom 960 patients (672 [70·0%] were male and 288 [30·0%] were female) were enrolled and randomly assigned (320 patients per group). The modified intention-to-treat population of 295 patients allocated to the 7-day high-dose primaquine group, 305 patients allocated to the tafenoquine group, and 301 patients allocated to the 14-day low-dose primaquine group were considered at risk of P vivax recurrence from day 15 onwards. The cumulative incidence of P vivax recurrence at 6 months was 13·0% (97·55% CI 9·0-18·5) in the 7-day high-dose primaquine group and 18·5% (13·8-24·6) in the 14-day low-dose primaquine group (hazard ratio [HR] 0·66 [97·55% CI 0·40-1·09], p=0·063). The corresponding incidence in the tafenoquine group was 12·6% (97·55% CI 8·8-18·0), with an HR of 0·64 (97·55% CI 0·39-1·05, p=0·041) compared with the 14-day low-dose primaquine group. Of the adverse events occurring before day 42, 24 (42·9%) of 56 were considered drug related in the 7-day high-dose primaquine group, compared with 16 (22·2%) of 72 in the tafenoquine group and 13 (34·2%) of 38 in the 14-day low-dose primaquine group. Four serious adverse events occurred, of which two (gastrointestinal symptoms in two patients in the 7-day high-dose primaquine group) were considered probably related to study drug. One study drug unrelated death occurred in the 14-day low-dose primaquine group.
interpretationBoth unsupervised 7-day high-dose primaquine and single-dose tafenoquine were well tolerated in patients with normal G6PD activity and they had a lower risk of P vivax recurrence compared with those in the 14-day low-dose primaquine group, albeit with uncertain magnitude. Our findings support the effectiveness and operational feasibility of shorter radical cure regimens across diverse malaria-endemic settings.
fundingNational Health and Medical Research Council of Australia and Bill and Melinda Gates Foundation.
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