Vivax MalariaPhase 4NCT04706130
Rigorous Assessment of P. Vivax Relapses and Primaquine Efficacy for Radical Cure
A Phase 4 study testing Primaquine and Artesunate in people with Vivax Malaria, run by University of Maryland, Baltimore at 1 site in Cambodia.
Trial summary
The study will be an open-labelled randomized clinical trial to determine therapeutic efficacy. Note that this will not be an Investigational New Drug application, as only World Health Organization (WHO)-approved drugs will be used at dosage and for conditions approved. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Vivax Malaria
- What is being tested?
- Primaquine and Artesunate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 1 siteCambodia
- Study dates
- 15 Apr 2021to 1 Oct 2024
- Phase
- Phase 4
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 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 15 and older
- Acute (within 10 days), symptomatic (i.e., history of fever), uncomplicated malaria caused solely by Plasmodium vivax (verified by PCR)
- G6PD normal (as determined by quantitative spectrophotometric assay)
Who cannot join
- Pregnant, planning to become pregnant or lactating women,
- Received antimalarial drugs in the past month,
- Hb < 8g/dL, < 1,500 neutrophils/μl, or signs of complicated malaria (e.g., vomiting, convulsions,…),
- History of primaquine, artesunate or artesunate-mefloquine allergy or intolerance,
- PCR-positivity for severe acute respiratory syndrome coronavirus 2.
Trial locations and contacts
1 site in 1 country.
About this study
The study will be an open-labelled randomized clinical trial to determine therapeutic efficacy. Note that this will not be an Investigational New Drug application, as only World Health Organization (WHO)-approved drugs will be used at dosage and for conditions approved.
Read the detailed description
The study will be an open-labelled randomized clinical trial to determine therapeutic efficacy. Note that this will not be an Investigational New Drug application, as only World Health Organization-approved drugs will be used at dosage and for conditions approved.
Eligible patients willing to participate will first be tested prior to enrolment for their glucose-6-phosphate dehydrogenase (G6PD) status by the gold standard spectrophotometric analysis. The investigators will exclude from the study any G6PD deficient (or intermediate females) patient. Treatment allocation will be randomized between i) 7 days of artesunate (2 mg/kg/day for 7 days) alone (Arm1), ii) same artesunate regimen + 0.25 mg/kg/day 14 days of primaquine (Arm2) and iii) same artesunate regimen + 0.5 mg/kg/day 14 days of primaquine (Arm3). All patients will be relocated to a no-transmission city to make sure they are not reinfected during the follow-up. Follow-up will be performed every 24-48h for 90 days. At the end of the follow-up period, all patients that did not receive primaquine (arm1) will be treated according to national guidelines (14 days at 0.25mg/kg/day). Patients will additionally be followed monthly for three months after the end of the relocation.
- Conditions
- Vivax Malaria
- Being tested
- Primaquine, Artesunate
- Medical subject headings
- Malaria, Vivax
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrimaquineDrug
After treatment of the blood stage infection, enrolled participants will receive either no primaquine, a low dose of primaquine or a high dose of primaquine against liver parasites
ArtesunateDrug
All enrolled participants will receive a 7-day treatment of artesunate ((2 mg/kg/day) to clear blood-stage parasites
| Study group | Role | What they receive |
|---|---|---|
| Arm1: No primaquine | Other | Enrolled patients will only received blood stage antimalarial (artesunate at 2 mg/kg per day every 24h for 7 days) Receives: Drug: Artesunate |
| Arm2: Primaquine low dose | Other | Enrolled patients will received blood stage antimalarial (artesunate at 2 mg/kg per day every 24h for 7 days) and primaquine at 0.25 mg/kg/day for 14 days (starting at day 7) Receives: Drug: Primaquine; Drug: Artesunate |
| Arm3: Primaquine high dose | Other | Enrolled patients will received blood stage antimalarial (artesunate at 2 mg/kg per day every 24h for 7 days) and primaquine at 0.50 mg/kg/day for 14 days (starting at day 7) Receives: Drug: Primaquine; Drug: Artesunate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Experiencing P. Vivax Recurrence
Number of patients experiencing recurrence as measured by microscopy and PCR and time to recurrence
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2021
- Study start15 Apr 2021
- Primary completion1 Oct 2024
- Study completion1 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The study will be an open-labelled randomized clinical trial to determine therapeutic efficacy.
- Masking
- None (open label)
- Enrolment
- 160 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Collaborators
- National Centre for Parasitology, Entomology and Malaria Control, Cambodia, Institut Pasteur du Cambodge
- Responsible party
- Principal investigator, David Serre, University of Maryland, Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04706130
- Sponsor's protocol ID
- 20-0010
- Status last verified
- May 2026
- First submitted
- 8 Jan 2021
- Last updated
- 3 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Eng V, Lek D, Sin S, Feufack-Donfack LB, Orban A, Salvador J, Seng D, Heng S, Khim N, Tebben K, Flamand C, Sommen C, van der Pluijm RW, White M, Witkowski B, Serre D, Popovici J. 14 days of high-dose versus low-dose primaquine treatment in patients with Plasmodium vivax infection in Cambodia: a randomised, single-centre, open-label efficacy study. Lancet Infect Dis. 2025 Aug;25(8):884-895. doi: 10.1016/S1473-3099(25)00033-7. Epub 2025 Mar 17.
PubMed 40112852Eng V, Lek D, Sin S, Feufack-Donfack LB, Orban A, Salvador J, Seng D, Heng S, Khim N, Tebben K, Flamand C, Sommen C, van der Pluijm RW, White M, Witkowski B, Serre D, Popovici J. High versus low dose of 14 days treatment of primaquine in Plasmodium vivax infected patients in Cambodia: a randomised open-label efficacy study. medRxiv [Preprint]. 2025 Jan 2:2025.01.01.25319862. doi: 10.1101/2025.01.01.25319862.
PubMed 39802788