MalariaPhase 4PRIMANCT03916003
Reducing the Risk of P. Vivax After Falciparum Infections in Co-endemic Areas
A Phase 4 study testing primaquine in people with Malaria and Vivax Malaria, run by Menzies School of Health Research at 3 sites in 3 countries.
Trial summary
This study is designed as a multi-centre randomized, open label trial to compare the safety and efficacy of a high dose primaquine (PQ) treatment in G6PD normal patients with P. falciparum to reduce the risk of subsequent P. vivax episodes to current standard practice of providing only schizontocidal treatment. Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- Malaria, Vivax Malaria, Falciparum Malaria
- What is being tested?
- primaquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 500 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 18 Aug 2019to 30 Jul 2022
- Phase
- Phase 4
- 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 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- P. falciparum mono-infection
- Fever (axillary temperature ≥37.5⁰C) or history of fever in preceding 48 hours
- Age >1 years (≥ 18 years at the Ethiopia site)
- G6PD normal as defined by the Biosensor (SD Biosensor, ROK) at ≥70% of the adjusted male median (AMM) for each site
- Written informed consent
- Able to comply with all study procedures and timelines
Who cannot join
- General danger signs or symptoms of severe malaria
- Anaemia, defined as Hb <8g/dl
- Pregnant women as determined by Urine β-HCG pregnancy test
- Breast feeding women
- Known hypersensitivity to any of the drugs given
- Regular use of drugs with haemolytic potential
- Blood transfusion within the last 4 months
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
About this study
Official title: Reducing the Risk of P. Vivax After Falciparum Infections in Co-endemic Areas - a Randomized Controlled Trial
This study is designed as a multi-centre randomized, open label trial to compare the safety and efficacy of a high dose primaquine (PQ) treatment in G6PD normal patients with P. falciparum to reduce the risk of subsequent P. vivax episodes to current standard practice of providing only schizontocidal treatment.
Read the detailed description
Plasmodium vivax forms dormant liver stages that reactivate weeks or months following an acute infection. Recurrent infections can be associated with a febrile illness, a cumulative risk of severe anaemia, direct and indirect mortality, and are the most important source of onward transmission of the parasite. In co-endemic areas, there is a very high risk (up to 50%) of patients representing with P. vivax malaria following treatment of P. falciparum. Hence, in co-endemic regions there is a strong rationale for eradicating P. vivax hypnozoites from the liver in patients presenting with uncomplicated P. falciparum infections.
The recently completed multicentre IMPROV study compared the efficacy of a 7 day primaquine regimen (1.0 mg/kg/day for 7 days) with a 14 day regimen (0.5 mg/kg/day for 14 days). The 7 day PQ regimen was non-inferior to the 14 day regimen and 5-fold more efficacious at reducing P. vivax recurrence than the control.
This study is designed as a multicentre randomized, open label trial to compare the safety and efficacy of a high dose PQ treatment in G6PD normal patients with P. falciparum to reduce the risk of subsequent P. vivax episodes to current standard practice of providing only schizontocidal treatment.
- Conditions
- Malaria, Vivax Malaria, Falciparum Malaria
- Being tested
- primaquine
- Medical subject headings
- Malaria, Malaria, Vivax, Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
primaquineDrug
Primaquine regimen over 7 days (1.0 mg/kg/day for 7 days)
| Study group | Role | What they receive |
|---|---|---|
| PQ7 | Experimental | high dose primaquine regimen over 7 days (1.0 mg/kg/day for 7 days) Receives: Drug: primaquine |
| standard care | No intervention | As per national guidelines for P. falciparum treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence risk of any P. vivax parasitaemia at day 63
The incidence risk of any P. vivax parasitaemia at day 63
Measured: 63 days
Secondary outcomes (12)
Incidence risk of symptomatic P. vivax parasitaemia at day 63
incidence risk of symptomatic P. vivax parasitaemia at day 63
Measured: 63 days
Incidence risk of all any P. vivax parasitaemia at day 28 and 42
Incidence risk of all any P. vivax parasitaemia at day 28 and 42
Measured: 28 and 42 days
Incidence risk of any P. falciparum malaria at day 28, 42 and 63
incidence risk of any P. falciparum malaria at day 28, 42 and 63
Measured: 28/42/63 days
proportion of patients vomiting their medication within 1 hour of administration
proportion of patients vomiting their medication on the day of enrollment within 1 hour of administration
Measured: 1 hour
proportion of patients vomiting any of their PQ doses within 1 hour of administration
proportion of patients vomiting any of their PQ doses within 1 hour of administration
Measured: 7 days
proportion of adverse events and serious adverse events
proportion of adverse events and serious adverse events
Measured: 63 days
incidence risk of severe anaemia (Hb<5g/dl) and moderately severe anaemia (<7g/dl) and/or the risk for blood transfusion between day 3 and 7
incidence risk of severe anaemia (Hb<5g/dl) and moderately severe anaemia (<7g/dl) and/or the risk for blood transfusion between day 3 and 7
Measured: 7 days
• The incidence risk of ≥25% fall in haemoglobin since baseline with and without hemoglobinuria at day 3 and day 7
- The incidence risk of ≥25% fall in haemoglobin since baseline with and without hemoglobinuria at day 3 and day 7
Measured: 7 days
The incidence risk of ≥25% fall in haemoglobin to under 7g/dl with and without hemoglobinuria at day 3 and day 7
The incidence risk of ≥25% fall in haemoglobin to under 7g/dl with and without hemoglobinuria at day 3 and day 7
Measured: day 7
Incidence risk of P. falciparum gametocytaemia between day 7 and 63
Incidence risk of P. falciparum gametocytaemia between day 7 and 63
Measured: 63 days
Parasite clearance on day 1, 2 and 3
Parasite clearance on day 1, 2 and 3
Measured: 3 days
Fever clearance on day 1, 2 and 3
Fever clearance on day 1, 2 and 3
Measured: 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2019
- Study start18 Aug 2019
- Primary completion14 May 2022
- Study completion30 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for 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
- Masking
- None (open label)
- Enrolment
- 500 participants (actual)
Sponsor and investigators
- Lead sponsor
- Menzies School of Health Research
- Sponsor type
- University, hospital or other
- Collaborators
- International Centre for Diarrhoeal Disease Research, Bangladesh, Tribhuvan University, Nepal, Arba Minch University, Addis Ababa University
- Responsible party
- Sponsor
- Investigators
- Kamala Thriemer, MD, Principal investigator, Menzies School of Health Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03916003
- Sponsor's protocol ID
- 19-3288
- Acronym
- PRIMA
- Status last verified
- Nov 2023
- First submitted
- 12 Apr 2019
- Last updated
- 21 Nov 2023
- 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
Vernandes M, Agustine W, Fadilah I, Christian M, Rumaseb A, Subekti D, Louisa M, Price RN, Thriemer K, Baird JK. Primaquine-derived 5,6-orthoquinone concentrations in urine associated with CYP2D6 genotype-predicted phenotype and blood methemoglobin levels. Antimicrob Agents Chemother. 2026 Aug 5;70(8):e0053926. doi: 10.1128/aac.00539-26. Epub 2026 Jul 13.
PubMed 42439801Thriemer K, Degaga TS, Christian M, Alam MS, Rajasekhar M, Ley B, Hossain MS, Kibria MG, Tego TT, Abate DT, Weston S, Mnjala H, Rumaseb A, Satyagraha AW, Sadhewa A, Panggalo LV, Ekawati LL, Lee G, Anose RT, Kiros FG, Simpson JA, Karahalios A, Woyessa A, Baird JK, Sutanto I, Hailu A, Price RN. Primaquine radical cure in patients with Plasmodium falciparum malaria in areas co-endemic for P falciparum and Plasmodium vivax (PRIMA): a multicentre, open-label, superiority randomised controlled trial. Lancet. 2023 Dec 2;402(10417):2101-2110. doi: 10.1016/S0140-6736(23)01553-2. Epub 2023 Nov 15.
PubMed 37979594Thriemer K, Degaga TS, Christian M, Alam MS, Ley B, Hossain MS, Kibria MG, Tego TT, Abate DT, Weston S, Karahalios A, Rajasekhar M, Simpson JA, Rumaseb A, Mnjala H, Lee G, Anose RT, Kidane FG, Woyessa A, Baird K, Sutanto I, Hailu A, Price RN. Reducing the risk of Plasmodium vivax after falciparum infections in co-endemic areas-a randomized controlled trial (PRIMA). Trials. 2022 May 18;23(1):416. doi: 10.1186/s13063-022-06364-z.
PubMed 35585641
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reducing the Risk of P. Vivax After Falciparum Infections in Co-endemic Areas - a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03916003
- Acronym / sponsor ID
- PRIMA / 19-3288
- Conditions
- Malaria, Vivax Malaria, Falciparum Malaria
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 500 participants (actual)
- Lead sponsor
- Menzies School of Health ResearchUniversity, hospital or other
- Collaborators
- International Centre for Diarrhoeal Disease Research, Bangladesh, Tribhuvan University, Nepal, Arba Minch University, Addis Ababa University
- Study start
- 18 Aug 2019 (actual)
- Primary completion
- 14 May 2022 (actual)
- Study completion
- 30 Jul 2022 (actual)
- First posted
- 16 Apr 2019 (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.
This study is designed as a multi-centre randomized, open label trial to compare the safety and efficacy of a high dose primaquine (PQ) treatment in G6PD normal patients with P. falciparum to reduce the risk of subsequent P. vivax episodes to current standard practice of providing only schizontocidal treatment.
Detailed description
Plasmodium vivax forms dormant liver stages that reactivate weeks or months following an acute infection. Recurrent infections can be associated with a febrile illness, a cumulative risk of severe anaemia, direct and indirect mortality, and are the most important source of onward transmission of the parasite. In co-endemic areas, there is a very high risk (up to 50%) of patients representing with P. vivax malaria following treatment of P. falciparum. Hence, in co-endemic regions there is a strong rationale for eradicating P. vivax hypnozoites from the liver in patients presenting with uncomplicated P. falciparum infections.
The recently completed multicentre IMPROV study compared the efficacy of a 7 day primaquine regimen (1.0 mg/kg/day for 7 days) with a 14 day regimen (0.5 mg/kg/day for 14 days). The 7 day PQ regimen was non-inferior to the 14 day regimen and 5-fold more efficacious at reducing P. vivax recurrence than the control.
This study is designed as a multicentre randomized, open label trial to compare the safety and efficacy of a high dose PQ treatment in G6PD normal patients with P. falciparum to reduce the risk of subsequent P. vivax episodes to current standard practice of providing only schizontocidal treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PQ7 | Experimental | Drug: primaquinehigh dose primaquine regimen over 7 days (1.0 mg/kg/day for 7 days) |
| standard care | No intervention | –As per national guidelines for P. falciparum treatment |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- P. falciparum mono-infection
- Fever (axillary temperature ≥37.5⁰C) or history of fever in preceding 48 hours
- Age >1 years (≥ 18 years at the Ethiopia site)
- G6PD normal as defined by the Biosensor (SD Biosensor, ROK) at ≥70% of the adjusted male median (AMM) for each site
- Written informed consent
Key exclusion criteria (7 listed)
- General danger signs or symptoms of severe malaria
- Anaemia, defined as Hb <8g/dl
- Pregnant women as determined by Urine β-HCG pregnancy test
- Breast feeding women
- Known hypersensitivity to any of the drugs given
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 |
|---|---|---|
| primaquinePrimaquine regimen over 7 days (1.0 mg/kg/day for 7 days) | Drug | PQ7 |
Primary outcome
Incidence risk of any P. vivax parasitaemia at day 63
Time frame: 63 days
The incidence risk of any P. vivax parasitaemia at day 63
12 secondary outcomes
Incidence risk of symptomatic P. vivax parasitaemia at day 63
Time frame: 63 days
Incidence risk of all any P. vivax parasitaemia at day 28 and 42
Time frame: 28 and 42 days
Incidence risk of any P. falciparum malaria at day 28, 42 and 63
Time frame: 28/42/63 days
proportion of patients vomiting their medication within 1 hour of administration
Time frame: 1 hour
proportion of patients vomiting any of their PQ doses within 1 hour of administration
Time frame: 7 days
proportion of adverse events and serious adverse events
Time frame: 63 days
incidence risk of severe anaemia (Hb<5g/dl) and moderately severe anaemia (<7g/dl) and/or the risk for blood transfusion between day 3 and 7
Time frame: 7 days
• The incidence risk of ≥25% fall in haemoglobin since baseline with and without hemoglobinuria at day 3 and day 7
Time frame: 7 days
The incidence risk of ≥25% fall in haemoglobin to under 7g/dl with and without hemoglobinuria at day 3 and day 7
Time frame: day 7
Incidence risk of P. falciparum gametocytaemia between day 7 and 63
Time frame: 63 days
Parasite clearance on day 1, 2 and 3
Time frame: 3 days
Fever clearance on day 1, 2 and 3
Time frame: 3 days
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 21 Nov 2023.
- Derived from this study: PubMed 42439801Vernandes M, Agustine W, Fadilah I, Christian M, Rumaseb A, Subekti D, Louisa M, Price RN, Thriemer K, Baird JK. Primaquine-derived 5,6-orthoquinone concentrations in urine associated with CYP2D6 genotype-predicted phenotype and blood methemoglobin levels. Antimicrob Agents Chemother. 2026 Aug 5;70(8):e0053926. doi: 10.1128/aac.00539-26. Epub 2026 Jul 13.
- Derived from this study: PubMed 37979594Thriemer K, Degaga TS, Christian M, Alam MS, Rajasekhar M, Ley B, Hossain MS, Kibria MG, Tego TT, Abate DT, Weston S, Mnjala H, Rumaseb A, Satyagraha AW, Sadhewa A, Panggalo LV, Ekawati LL, Lee G, Anose RT, Kiros FG, Simpson JA, Karahalios A, Woyessa A, Baird JK, Sutanto I, Hailu A, Price RN. Primaquine radical cure in patients with Plasmodium falciparum malaria in areas co-endemic for P falciparum and Plasmodium vivax (PRIMA): a multicentre, open-label, superiority randomised controlled trial. Lancet. 2023 Dec 2;402(10417):2101-2110. doi: 10.1016/S0140-6736(23)01553-2. Epub 2023 Nov 15.
- Derived from this study: PubMed 35585641Thriemer K, Degaga TS, Christian M, Alam MS, Ley B, Hossain MS, Kibria MG, Tego TT, Abate DT, Weston S, Karahalios A, Rajasekhar M, Simpson JA, Rumaseb A, Mnjala H, Lee G, Anose RT, Kidane FG, Woyessa A, Baird K, Sutanto I, Hailu A, Price RN. Reducing the risk of Plasmodium vivax after falciparum infections in co-endemic areas-a randomized controlled trial (PRIMA). Trials. 2022 May 18;23(1):416. doi: 10.1186/s13063-022-06364-z.
- 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 principal investigator
Menzies School of Health Research
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing primaquine in people with Malaria and Vivax Malaria, run by Menzies School of Health Research at 3 sites in 3 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 7 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 21 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Bangladesh, Ethiopia, Indonesia. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 of any P. vivax parasitaemia at day 63 (time frame: 63 days). 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 NCT03916003, which also lists 3 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 21 Nov 2023.