Malaria, VivaxPhase 2CHILDPRIMNCT05044637
Study to Evaluate Primaquine for Radical Cure of Uncomplicated Plasmodium Vivax Malaria in Children
A Phase 2 study testing Primaquine in people with Malaria, Vivax, run by Fundação de Medicina Tropical Dr. Heitor Vieira Dourado at 2 sites in Brazil.
Trial summary
The main determinant of primaquine efficacy is the total dose of primaquine administered, rather than the dosing schedule. Infants and children younger than 4 years of age are at a higher risk of frequent relapses than older age groups, which may lead to severe anaemia. Read more about this study
- Who is it for?
- Ages 6 months to 14 years
- Conditions the study is for
- Malaria, Vivax
- What is being tested?
- Primaquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 2 sitesBrazil
- Study dates
- 26 Aug 2021to 7 Jan 2025
- Phase
- Phase 2
- 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 6 months to 14 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Infection with P.vivax parasitaemia;
- ≥ 6 months and ˂ 15 years of age;
- Body weight ≥ 5 Kg;
- Hb > 7 g/dL
- presence of axillary temperature >37.5 Celsius or history of fever during the past 48 hours;
- ability to swallow oral medication;
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- Absence of severe malnutrition (defined as a child whose growth standard is below -3-Z-score, has symmetrical oedema involving at least the feet or has a mid-upper arm circumference < 110 mm)
- Absence of febrile conditions due to disease other than malaria (e.g., measles, acute lower respiratory tract infection, severe diarrhea with dehydration) or the known underlying chronic or severe diseases (e.g., cardiac, renal, hepatic diseases, HIV/AIDS);
- History of hypersensitivity reactions to or contraindicated for any of the medicine(s) being teste d or used as alternative treatment(s);
- A negative pregnancy test or non-lactating
- Ability and willingness to comply with the study protocol for the duration of the study, including 6 months of follow up;
- Informed consent from the patient/parent/guardian (with additional informed assent for any participant between 7 and 14 years of age);
- Pregnancy test consent from girls of childbearing age (defined as having had menarche) and their parents or guardians;
Who cannot join
- G6PD- Deficiency (< 4.0 U/g Hb)
- The subject has severe P. vivax malaria as defined by the World Health Organization (WHO) criteria
- intolerance of or allergy to one of the medications in the study
- Pregnant or breastfeeding women
- Inability to tolerate oral medication
- Blood tranfusion in the last 3 months (as this may mask the G6PD deficiency)
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- Serious or chronic medical condition (cardiac, renal, hepatic diseases, sickle cell disease, HIV/AIDS)
- History of malaria in the last 30 days
- Belonging to the indigenous community
Trial locations and contacts
2 sites in 1 country.
Brazil2 sites
Universidade Federal do Acre
Cruzeiro do Sul, Acre
Fundação de Medicina Tropical Doutor Heitor Vieira Dourado
Manaus, Amazonas, 69040-000
About this study
Official title: Phase IIB Study to Evaluate Primaquine Safety and Tolerability for Radical Cure of Uncomplicated Plasmodium Vivax Malaria in Children < 15 Years-old (CHILDPRIM)
The main determinant of primaquine efficacy is the total dose of primaquine administered, rather than the dosing schedule. Infants and children younger than 4 years of age are at a higher risk of frequent relapses than older age groups, which may lead to severe anaemia. In view of this issue, after Glucose-6-phosphate dehydrogenase (G6PD) testing, WHO recommends the use of a low dose (0·25 mg/kg of bodyweight) of primaquine for 14 days in infants aged 6 months and older, as a follow-up treatment for malaria caused by P. vivax and P. ovale. Nevertheless, previous trials have demonstrated that the standard low dose regimen of primaquine (3.5 mg/kg total) fails to prevent relapses in many different endemic locations. For this reason, the 2010 WHO antimalarial guidelines now recommend a high dose regimen of 7 mg/kg (equivalent to an adult dose of 30mg per day), although many countries still recommend lower doses for fear of causing more serious harm to unscreened G6PD deficiency patients.
The pharmacokinetics of several antimalarial drugs are different in children younger than 10 years of age or who are underweight for their age compared with children of 10 years and older and adults.The doses of several antimalarials in children are suboptimal. This oversight is a consequence of designing dosing regimens in a different population (i.e., adults) for the one most affected by the disease and this has led to revisions of some dosing recommendations. The different pharmacokinetic performance of drugs in children might also relate to maturation (e.g., of metabolic processes, particularly in the first 2 years of life). Pharmacogenomic factors affecting drug metabolism are increasingly being studied. Polymorphisms in cytochrome P4502D6 are associated with different primaquine metabolizer phenotypes with resulting differing efficacies for radical cure. Shorter courses of higher daily doses of primaquine have the potential to improve adherence and, thus, effectiveness without compromising efficacy. If the efficacy, tolerability and safety of short-course, high-dose primaquine regimens can be assured across the range of endemic settings, along with reliable point-of-care G6PD deficiency diagnostics, then this would be a major advance in malaria treatment by improving adherence and thus the effectiveness of anti-relapse therapy.
- Conditions
- Malaria, Vivax
- Being tested
- 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.
PrimaquineDrug
Also called Low-standard dose
7 days of unsupervised primaquine (3.5 mg/kg total dose) administered once per day (0.5 mg/kg OD).
PrimaquineDrug
Also called High-dose short course
7 days of unsupervised primaquine (7.0 mg/kg total dose) administered once per day (1.0 mg/kg OD).
PrimaquineDrug
Also called High-dose long course
14 days of unsupervised primaquine (7mg/kg total dose) administered once per day (0.5 mg/kg).
| Study group | Role | What they receive |
|---|---|---|
| Primaquine (3.5mg x 7d) | Experimental | Primaquine 7 days Standard blood schizontocidal therapy plus 7 days of unsupervised primaquine (3.5 mg/kg total dose) administered once per day (0.5 mg/kg OD). Receives: Drug: Primaquine |
| Primaquine (7.0mg x 7d) | Active comparator | Primaquine 7 days Standard blood schizontocidal therapy plus 7 days of unsupervised primaquine (7.0 mg/kg total dose) administered once per day (1.0 mg/kg OD). Receives: Drug: Primaquine |
| Primaquine (7.0mg x 14d) | Active comparator | Primaquine 14 days Standard blood schizontocidal therapy plus 14 days of unsupervised primaquine (7.0 mg/kg total dose) administered once per day (0.5 mg/kg). Receives: Drug: Primaquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety - Adverse Event
To diagnose, resolve and catalog adverse events of any intensity, whether clinical or laboratory
Measured: 6 months after randomization
Efficacy - Radical cure
The incidence rate (i.e., per person-year) of symptomatic recurrent P. vivax parasitaemia (detected by microscopy) over 6 months of follow-up in the 3.5 mg/Kg total dose versus 7.0 mg/Kg total dose primaquine groups
Measured: 6 months after randomization
Secondary outcomes (9)
Incidence rate (per person-year) of recurrent P. vivax
The overall incidence rate (per person-year) of any recurrent P. vivax parasitaemia detected by microscopy over 6 months of follow-up in the 3.5 mg/Kg total dose group versus the 7.0 mg/Kg total dose groups
Measured: 6 months after randomization
Incidence risk of any recurrent symptomatic P. vivax malaria
The incidence rate (per person-year) of any recurrent symptomatic P. vivax parasitaemia over 6 months of follow-up in either the 7-day or the 14-day primaquine arms of 7.0 mg/kg total dose compared with 7-day primaquine arm of 3.5 mg/Kg total dose.
Measured: 6 months after randomization
The hematological recovery in patients with vivax malaria
Hematological recovery will be assessed as the incidence risk of severe anaemia (Hb<7g/dl) and/or blood transfusion within the 6 month follow up period, and the mean fall in baseline Hb on day 7 and day 14. These outcomes will be compared between the treatment arms
Measured: 6 months after randomization
Proportion of patients with any adverse drug reactions
The proportion of patients with one or more adverse drug reactions within 42 days of their primary treatment and also at 6 months
Measured: 6 months after randomization
Primaquine tolerability 1 hour
Tolerability of primaquine will be assessed by comparing the proportion of patients with nausea, vomiting, abdominal pain and vomiting of a dose within 1 hour of administration between the treatment arms
Measured: 7 to 14 days after randomization
Primaquine tolerability
Drug tolerability between the treatment arms will also be assessed by comparing the proportion of patients completing a full course of primaquine therapy
Measured: 7 to 14 days after randomization
Pharmacogenetics CYP2D6
Characterize hepatic cytochrome CYP2D6 enzyme phenotypes using Activity Score A (AS-A)
Measured: 1 day after randomization
Genotype CYP2D6
Genotype CYP2D6 alleles in this study population
Measured: 1 day after randomization
Metabolomics
Describe the metabolic signatures present in patients with adverse events (AEs) and severe AEs (SAEs)
Measured: 28 days after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2021
- Study start26 Aug 2021
- Primary completion29 Jul 2024
- Study completion7 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Malaria, VivaxStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
- Sponsor type
- University, hospital or other
- Collaborators
- Bill and Melinda Gates Foundation, Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Responsible party
- Sponsor
- Investigators
- Maria das Graças C Alecrim, PhD, MD, Principal investigator, Fundação de Medicina Tropical - HVD
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05044637
- Sponsor's protocol ID
- CAAE: 50193921.6.1001.0005
- Acronym
- CHILDPRIM
- Status last verified
- Feb 2025
- First submitted
- 20 Aug 2021
- Last updated
- 20 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Pacheco ALO, Omena AG, Baia-da-Silva DC, Jardim TAP, Silva DCB, Lopes APB, Barbosa LRA, Souza IG, Araujo RF, Nogueira LOS, Vale SCN, Melo GC, Cordeiro JSM, Bassat Q, Sampaio VS, Lima VDS, Martinez-Espinosa FE, Mourao MPG, Monteiro WM, Alecrim MGC, Brito-Sousa JD, Lacerda MVG. Safety, tolerability, and efficacy of high versus low-dose, short versus long-course daily primaquine for the radical cure of uncomplicated Plasmodium vivax malaria in children under 15 years of age: an open-label, non-inferiority, randomized controlled trial (CHILDPRIM). Malar J. 2025 Dec 22;25(1):58. doi: 10.1186/s12936-025-05686-y.
PubMed 41430686
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IIB Study to Evaluate Primaquine Safety and Tolerability for Radical Cure of Uncomplicated Plasmodium Vivax Malaria in Children < 15 Years-old (CHILDPRIM)
- ClinicalTrials.gov ID
- NCT05044637
- Acronym / sponsor ID
- CHILDPRIM / CAAE: 50193921.6.1001.0005
- Conditions
- Malaria, Vivax
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Fundação de Medicina Tropical Dr. Heitor Vieira DouradoUniversity, hospital or other
- Collaborators
- Bill and Melinda Gates Foundation, Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Study start
- 26 Aug 2021 (actual)
- Primary completion
- 29 Jul 2024 (actual)
- Study completion
- 7 Jan 2025 (actual)
- First posted
- 16 Sep 2021 (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.
The main determinant of primaquine efficacy is the total dose of primaquine administered, rather than the dosing schedule. Infants and children younger than 4 years of age are at a higher risk of frequent relapses than older age groups, which may lead to severe anaemia. In view of this issue, after Glucose-6-phosphate dehydrogenase (G6PD) testing, WHO recommends the use of a low dose (0·25 mg/kg of bodyweight) of primaquine for 14 days in infants aged 6 months and older, as a follow-up treatment for malaria caused by P. vivax and P. ovale. Nevertheless, previous trials have demonstrated that the standard low dose regimen of primaquine (3.5 mg/kg total) fails to prevent relapses in many different endemic locations. For this reason, the 2010 WHO antimalarial guidelines now recommend a high dose regimen of 7 mg/kg (equivalent to an adult dose of 30mg per day), although many countries still recommend lower doses for fear of causing more serious harm to unscreened G6PD deficiency patients.
The pharmacokinetics of several antimalarial drugs are different in children younger than 10 years of age or who are underweight for their age compared with children of 10 years and older and adults.The doses of several antimalarials in children are suboptimal. This oversight is a consequence of designing dosing regimens in a different population (i.e., adults) for the one most affected by the disease and this has led to revisions of some dosing recommendations. The different pharmacokinetic performance of drugs in children might also relate to maturation (e.g., of metabolic processes, particularly in the first 2 years of life). Pharmacogenomic factors affecting drug metabolism are increasingly being studied. Polymorphisms in cytochrome P4502D6 are associated with different primaquine metabolizer phenotypes with resulting differing efficacies for radical cure. Shorter courses of higher daily doses of primaquine have the potential to improve adherence and, thus, effectiveness without compromising efficacy. If the efficacy, tolerability and safety of short-course, high-dose primaquine regimens can be assured across the range of endemic settings, along with reliable point-of-care G6PD deficiency diagnostics, then this would be a major advance in malaria treatment by improving adherence and thus the effectiveness of anti-relapse therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Primaquine (3.5mg x 7d) | Experimental | Drug: PrimaquinePrimaquine 7 days Standard blood schizontocidal therapy plus 7 days of unsupervised primaquine (3.5 mg/kg total dose) administered once per day (0.5 mg/kg OD). |
| Primaquine (7.0mg x 7d) | Active comparator | Drug: PrimaquinePrimaquine 7 days Standard blood schizontocidal therapy plus 7 days of unsupervised primaquine (7.0 mg/kg total dose) administered once per day (1.0 mg/kg OD). |
| Primaquine (7.0mg x 14d) | Active comparator | Drug: PrimaquinePrimaquine 14 days Standard blood schizontocidal therapy plus 14 days of unsupervised primaquine (7.0 mg/kg total dose) administered once per day (0.5 mg/kg). |
Who may qualify
- Ages
- 6 months to 14 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (13 listed)
- Infection with P.vivax parasitaemia;
- ≥ 6 months and ˂ 15 years of age;
- Body weight ≥ 5 Kg;
- Hb > 7 g/dL
- presence of axillary temperature >37.5 Celsius or history of fever during the past 48 hours;
Key exclusion criteria (9 listed)
- G6PD- Deficiency (< 4.0 U/g Hb)
- The subject has severe P. vivax malaria as defined by the World Health Organization (WHO) criteria
- intolerance of or allergy to one of the medications in the study
- Pregnant or breastfeeding women
- Inability to tolerate oral medication
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 |
|---|---|---|
| PrimaquineAlso: Low-standard dose7 days of unsupervised primaquine (3.5 mg/kg total dose) administered once per day (0.5 mg/kg OD). | Drug | Primaquine (3.5mg x 7d) |
| PrimaquineAlso: High-dose short course7 days of unsupervised primaquine (7.0 mg/kg total dose) administered once per day (1.0 mg/kg OD). | Drug | Primaquine (7.0mg x 7d) |
| PrimaquineAlso: High-dose long course14 days of unsupervised primaquine (7mg/kg total dose) administered once per day (0.5 mg/kg). | Drug | Primaquine (7.0mg x 14d) |
Primary outcome
Safety - Adverse Event
Time frame: 6 months after randomization
To diagnose, resolve and catalog adverse events of any intensity, whether clinical or laboratory
Efficacy - Radical cure
Time frame: 6 months after randomization
The incidence rate (i.e., per person-year) of symptomatic recurrent P. vivax parasitaemia (detected by microscopy) over 6 months of follow-up in the 3.5 mg/Kg total dose versus 7.0 mg/Kg total dose primaquine groups
9 secondary outcomes
Incidence rate (per person-year) of recurrent P. vivax
Time frame: 6 months after randomization
Incidence risk of any recurrent symptomatic P. vivax malaria
Time frame: 6 months after randomization
The hematological recovery in patients with vivax malaria
Time frame: 6 months after randomization
Proportion of patients with any adverse drug reactions
Time frame: 6 months after randomization
Primaquine tolerability 1 hour
Time frame: 7 to 14 days after randomization
Primaquine tolerability
Time frame: 7 to 14 days after randomization
Pharmacogenetics CYP2D6
Time frame: 1 day after randomization
Genotype CYP2D6
Time frame: 1 day after randomization
Metabolomics
Time frame: 28 days after randomization
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 20 Feb 2025.
- Derived from this study: PubMed 41430686Pacheco ALO, Omena AG, Baia-da-Silva DC, Jardim TAP, Silva DCB, Lopes APB, Barbosa LRA, Souza IG, Araujo RF, Nogueira LOS, Vale SCN, Melo GC, Cordeiro JSM, Bassat Q, Sampaio VS, Lima VDS, Martinez-Espinosa FE, Mourao MPG, Monteiro WM, Alecrim MGC, Brito-Sousa JD, Lacerda MVG. Safety, tolerability, and efficacy of high versus low-dose, short versus long-course daily primaquine for the radical cure of uncomplicated Plasmodium vivax malaria in children under 15 years of age: an open-label, non-inferiority, randomized controlled trial (CHILDPRIM). Malar J. 2025 Dec 22;25(1):58. doi: 10.1186/s12936-025-05686-y.
- Individual participant dataSharing planned: Undecided
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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.
Maria das Graças C Alecrim, PhD, MD principal investigator
Fundação de Medicina Tropical - HVD
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Primaquine in people with Malaria, Vivax, run by Fundação de Medicina Tropical Dr. Heitor Vieira Dourado at 2 sites in Brazil.
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 13 inclusion and 9 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 20 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Brazil. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Safety - Adverse Event (time frame: 6 months after randomization). The study lists 2 primary outcomes in all. 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 NCT05044637, which also lists 1 linked publication.
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 20 Feb 2025.