Vivax MalariaPhase 3EFFORTNCT04411836
Effectiveness of Novel Approaches to Radical Cure With Tafenoquine and Primaquine
A Phase 3 study testing Tafenoquine and Primaquine in people with Vivax Malaria and Plasmodium Vivax, run by Menzies School of Health Research at 6 sites in 4 countries.
Trial summary
Health care facility based, randomized, controlled, open label, superiority trial with 3 arms Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Vivax Malaria, Plasmodium Vivax, Malaria, Vivax
- What is being tested?
- Tafenoquine and Primaquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 960 participants
- Where
- 6 sitesin 4 countries
- Study dates
- 25 Apr 2021to 30 Sep 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- P. vivax peripheral parasitaemia (mono-infection) as determined by microscopy
- G6PD normal status (G6PD activity ≥ 70% of the adjusted male median as determined by the Biosensor™ (SD Biosensor, ROK))
- Fever (temperature ≥37.5⁰C) or history of fever in the preceding 48 hours
- Age ≥18 years
- Written informed consent
- Living in the study area and willing to be followed for six months
Who cannot join
- Danger signs or symptoms of severe malaria
- Anaemia (defined as Hb <8g/dl)
- Pregnant or lactating females
- Known hypersensitivity to any of the study drugs
- Regular use of drugs with haemolytic potential
Trial locations and contacts
6 sites in 4 countries.
6 sites in 4 countries
Cambodia3 sites
Chambak Health Center
Kampong Speu
Kravanh District Hospital
Pursat, Pursat
Siem Pang Health Centre
Stung Treng
About this study
Official title: Effectiveness of Novel Approaches to Radical Cure With Tafenoquine and Primaquine - a Randomized Controlled Trial in P. Vivax Patients
Health care facility based, randomized, controlled, open label, superiority trial with 3 arms
Read the detailed description
- To assess the effectiveness of a short-course of high dose primaquine (total dose 7mg/kg given unsupervised over 7 days) compared to the current standard low dose primaquine regimen (total dose 3.5mg/kg given unsupervised over 14 days).
- To assess the effectiveness of tafenoquine (single dose of 300mg) compared to the short-course high dose primaquine regimen.
- To assess the safety of tafenoquine compared to the high and low dose primaquine regimens.
- To assess the cost-effectiveness and feasibility of high dose primaquine and tafenoquine compared to the current low dose primaquine regimen
- Conditions
- Vivax Malaria, Plasmodium Vivax, Malaria, Vivax, Malaria Relapse
- Being tested
- Tafenoquine, Primaquine
- Keywords
- tafenoquine, primaquine
- Medical subject headings
- Malaria, Vivax
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TafenoquineDrug
patients are treated with schizontocidal treatment plus a single dose of Tafenoquine (TQ).
PrimaquineDrug
Also called Primaquine 7 days
patients are treated with schizontocidal treatment plus high dose PQ (total dose 7 mg/kg) unsupervised over 7 days (PQ7)
| Study group | Role | What they receive |
|---|---|---|
| Control | No intervention | Patients are treated with schizontocidal treatment plus low dose PQ (total dose 3.5mg/kg) unsupervised over 14 days (PQ14) |
| PQ Intervention | Experimental | Patients are treated with schizontocidal treatment plus high dose PQ (total dose 7 mg/kg) unsupervised over 7 days (PQ7) Receives: Drug: Primaquine |
| TQ Intervention | Experimental | Patients are treated with schizontocidal treatment plus a single dose of Tafenoquine (TQ) Receives: Drug: Tafenoquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence risk any P vivax PQ7 / PQ14
The incidence risk (time to first event) of any P. vivax parasitaemia during the 6-month follow up period as determined by microscopy compared between the PQ7 arm and the control arm (PQ14).
Measured: 6 months
Secondary outcomes (5)
Incidence risk any P vivax PQ7 / TQ
The incidence risk (time to first event) of any P. vivax parasitaemia during the 6 months follow up period as determined by microscopy compared between PQ7 and TQ arms
Measured: 6 months
Incidence risk symptomatic P vivax TQ / PQ14
The incidence risk (time to first event) of symptomatic P. vivax parasitaemia during the 6 months follow up period as determined by microscopy compared between TQ and the control arm (PQ14).
Measured: 6 months
Incidence risk any P vivax PQ7 / PQ14
The incidence risk (time to first event) of symptomatic P. vivax parasitaemia during the 6-month follow up period as determined by microscopy compared between the PQ7 arm and the control arm (PQ14).
Measured: 6 months
Incidence risk any P vivax PQ7 / TQ
- The incidence risk (time to first event) of any P. vivax parasitaemia during the 6 months follow up period as determined by microscopy compared between PQ7 and TQ arms
Measured: 6 months
Incidence risk any P vivax PQ14 / TQ
The incidence risk (time to first event) of any P. vivax parasitaemia during the 6 months follow up period as determined by microscopy compared between PQ14 and TQ arms
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2020
- Study start25 Apr 2021
- Primary completion30 Sep 2024
- Study completion30 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Vivax MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 960 participants (actual)
Sponsor and investigators
- Lead sponsor
- Menzies School of Health Research
- Sponsor type
- University, hospital or other
- Collaborators
- University of Melbourne, National Centre for Parasitology, Entomology and Malaria Control, Cambodia, Mahidol Oxford Tropical Medicine Research Unit, Ethiopian Public Health Institute, Universitas Sumatera Utara, Arba Minch University, Aga Khan University
- Responsible party
- Sponsor
- Investigators
- Kamala Thriemer, MD, MPH, PhD, Principal investigator, Menzies School of Health Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04411836
- Sponsor's protocol ID
- EFFORT
- Acronym
- EFFORT
- Status last verified
- Oct 2024
- First submitted
- 28 May 2020
- Last updated
- 8 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Study Protocol and Statistical Analysis Plan will be made available to others. Data collected for the study, including individual patient data and the final trial dataset are reserved for the chief investigator and co-investigators of the trial. The trial will be reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines. Trial results will be published in peer-reviewed open access journals and disseminated to trial stakeholders, including participants, as per ethical guidelines.
Publications
Cassidy-Seyoum SA, Adhikari B, Mwaura M, Khan A, Zaidi SE, Azizullah Z, Qurashi B, Gellebo K, Bamboro SA, Ean M, Tripura R, Vattanak H, Vanda T, Sovann K, Simvieng O, Chanpheakdey P, Mnjala H, Lee G, Ghanchi N, Cheah PY, Price RN, Beg MA, Degaga TS, Dysoley L, Thriemer K. Dissemination of trial results to study participants in Cambodia, Ethiopia and Pakistan: a qualitative study. BMJ Open. 2026 Aug 10;16(8):e119698. doi: 10.1136/bmjopen-2026-119698.
PubMed 42575554Degaga TS, Pasaribu AP, Tripura R, Ghanchi N, Rajasekhar M, Adhikari B, Ley B, Bamboro SA, Jabbar FA, Hasibuan N, Tego TT, Zehra S, Qurashi B, Mnjala H, Lee G, Li P, Kazi AM, Safitri W, Yulita Y, Siagian DSP, Syahputra D, Hadi H, Muhammad T, Ibrahim A, Syed N, Dost K, Puspitrasari AM, Kariodimedjo PP, Rai A, Rumaseb A, Sutanto E, Ean M, Khan A, Sokha M, Commons RJ, Weston S, Noviyanti R, Peto T, Callery JJ, Ali U, Mehmood T, Dondorp A, Devine A, Setiawan E, Mwaura M, Cassidy-Seyoum S, Temesgen R, Abate DT, Erjabo EB, Gessa GG, Kiros FG, Usmani MI, Raza A, Woyessa A, Hailu A, Simpson JA, Karahalios A, Beg MA, von Seidlein L, Dysoley L, Auburn S, Price RN, Thriemer K. 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. Lancet Infect Dis. 2026 Jun;26(6):614-626. doi: 10.1016/S1473-3099(25)00729-7. Epub 2026 Feb 11.
PubMed 41690325
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectiveness of Novel Approaches to Radical Cure With Tafenoquine and Primaquine - a Randomized Controlled Trial in P. Vivax Patients
- ClinicalTrials.gov ID
- NCT04411836
- Acronym / sponsor ID
- EFFORT / EFFORT
- Conditions
- Vivax Malaria, Plasmodium Vivax, Malaria, Vivax, Malaria Relapse
- Keywords
- tafenoquine, primaquine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 960 participants (actual)
- Lead sponsor
- Menzies School of Health ResearchUniversity, hospital or other
- Collaborators
- University of Melbourne, National Centre for Parasitology, Entomology and Malaria Control, Cambodia, Mahidol Oxford Tropical Medicine Research Unit, Ethiopian Public Health Institute, Universitas Sumatera Utara, Arba Minch University, Aga Khan University
- Study start
- 25 Apr 2021 (actual)
- Primary completion
- 30 Sep 2024 (actual)
- Study completion
- 30 Sep 2024 (actual)
- First posted
- 2 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Health care facility based, randomized, controlled, open label, superiority trial with 3 arms
Detailed description
- To assess the effectiveness of a short-course of high dose primaquine (total dose 7mg/kg given unsupervised over 7 days) compared to the current standard low dose primaquine regimen (total dose 3.5mg/kg given unsupervised over 14 days).
- To assess the effectiveness of tafenoquine (single dose of 300mg) compared to the short-course high dose primaquine regimen.
- To assess the safety of tafenoquine compared to the high and low dose primaquine regimens.
- To assess the cost-effectiveness and feasibility of high dose primaquine and tafenoquine compared to the current low dose primaquine regimen
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Control | No intervention | –Patients are treated with schizontocidal treatment plus low dose PQ (total dose 3.5mg/kg) unsupervised over 14 days (PQ14) |
| PQ Intervention | Experimental | Drug: PrimaquinePatients are treated with schizontocidal treatment plus high dose PQ (total dose 7 mg/kg) unsupervised over 7 days (PQ7) |
| TQ Intervention | Experimental | Drug: TafenoquinePatients are treated with schizontocidal treatment plus a single dose of Tafenoquine (TQ) |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- P. vivax peripheral parasitaemia (mono-infection) as determined by microscopy
- G6PD normal status (G6PD activity ≥ 70% of the adjusted male median as determined by the Biosensor™ (SD Biosensor, ROK))
- Fever (temperature ≥37.5⁰C) or history of fever in the preceding 48 hours
- Age ≥18 years
- Written informed consent
Key exclusion criteria (5 listed)
- Danger signs or symptoms of severe malaria
- Anaemia (defined as Hb <8g/dl)
- Pregnant or lactating females
- Known hypersensitivity to any of the study drugs
- Regular use of drugs with haemolytic potential
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tafenoquinepatients are treated with schizontocidal treatment plus a single dose of Tafenoquine (TQ). | Drug | TQ Intervention |
| PrimaquineAlso: Primaquine 7 dayspatients are treated with schizontocidal treatment plus high dose PQ (total dose 7 mg/kg) unsupervised over 7 days (PQ7) | Drug | PQ Intervention |
Primary outcome
Incidence risk any P vivax PQ7 / PQ14
Time frame: 6 months
The incidence risk (time to first event) of any P. vivax parasitaemia during the 6-month follow up period as determined by microscopy compared between the PQ7 arm and the control arm (PQ14).
5 secondary outcomes
Incidence risk any P vivax PQ7 / TQ
Time frame: 6 months
Incidence risk symptomatic P vivax TQ / PQ14
Time frame: 6 months
Incidence risk any P vivax PQ7 / PQ14
Time frame: 6 months
Incidence risk any P vivax PQ7 / TQ
Time frame: 6 months
Incidence risk any P vivax PQ14 / TQ
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2024.
- Derived from this study: PubMed 42575554Cassidy-Seyoum SA, Adhikari B, Mwaura M, Khan A, Zaidi SE, Azizullah Z, Qurashi B, Gellebo K, Bamboro SA, Ean M, Tripura R, Vattanak H, Vanda T, Sovann K, Simvieng O, Chanpheakdey P, Mnjala H, Lee G, Ghanchi N, Cheah PY, Price RN, Beg MA, Degaga TS, Dysoley L, Thriemer K. Dissemination of trial results to study participants in Cambodia, Ethiopia and Pakistan: a qualitative study. BMJ Open. 2026 Aug 10;16(8):e119698. doi: 10.1136/bmjopen-2026-119698.
- Derived from this study: PubMed 41690325Degaga TS, Pasaribu AP, Tripura R, Ghanchi N, Rajasekhar M, Adhikari B, Ley B, Bamboro SA, Jabbar FA, Hasibuan N, Tego TT, Zehra S, Qurashi B, Mnjala H, Lee G, Li P, Kazi AM, Safitri W, Yulita Y, Siagian DSP, Syahputra D, Hadi H, Muhammad T, Ibrahim A, Syed N, Dost K, Puspitrasari AM, Kariodimedjo PP, Rai A, Rumaseb A, Sutanto E, Ean M, Khan A, Sokha M, Commons RJ, Weston S, Noviyanti R, Peto T, Callery JJ, Ali U, Mehmood T, Dondorp A, Devine A, Setiawan E, Mwaura M, Cassidy-Seyoum S, Temesgen R, Abate DT, Erjabo EB, Gessa GG, Kiros FG, Usmani MI, Raza A, Woyessa A, Hailu A, Simpson JA, Karahalios A, Beg MA, von Seidlein L, Dysoley L, Auburn S, Price RN, Thriemer K. 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. Lancet Infect Dis. 2026 Jun;26(6):614-626. doi: 10.1016/S1473-3099(25)00729-7. Epub 2026 Feb 11.
- Individual participant dataSharing planned: Yes. Study Protocol and Statistical Analysis Plan will be made available to others. Data collected for the study, including individual patient data and the final trial dataset are reserved for the chief investigator and co-investigators of the trial. The trial will be reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines. Trial results will be published in peer-reviewed open access journals and disseminated to trial stakeholders, including participants, as per ethical guidelines.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kamala Thriemer, MD, MPH, PhD principal investigator
Menzies School of Health Research
6 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tafenoquine and Primaquine in people with Vivax Malaria and Plasmodium Vivax, run by Menzies School of Health Research at 6 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Cambodia, Ethiopia, Indonesia, Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence risk any P vivax PQ7 / PQ14 (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04411836, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2024; AzTrials last refreshed its copy on 8 Nov 2026.