Study to Evaluate Primaquine for Radical Cure of Uncomplicated Plasmodium Vivax Malaria in Children

NCT05044637 | Completed Phase 2 DMC

• 1 other identifier: CAAE: 50193921.6.1001.0005
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

Brief 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. 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

Outcome Measures

Primary Outcomes (2)

• Safety - Adverse Event

  To diagnose, resolve and catalog adverse events of any intensity, whether clinical or laboratory

  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

  6 months after randomization

Secondary Outcomes (9)

• Incidence rate (per person-year) of recurrent P. vivax

  6 months after randomization

• Incidence risk of any recurrent symptomatic P. vivax malaria

  6 months after randomization

• The hematological recovery in patients with vivax malaria

  6 months after randomization

• Proportion of patients with any adverse drug reactions

  6 months after randomization

• Primaquine tolerability 1 hour

  7 to 14 days after randomization

Other Outcomes (4)

• Exploratory - Pharmacokinetics of primaquine Area Under the Curve (AUC)

  24 hours

• Exploratory - Pharmacokinetics of primaquine Conc

  24 hours

• Exploratory - Pharmacokinetics of primaquine Elimination rate

  24 hours

Study Arms (3)

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).

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).

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).

Drug: Primaquine

Interventions

Primaquine DRUG

7 days of unsupervised primaquine (3.5 mg/kg total dose) administered once per day (0.5 mg/kg OD).

Also known as: Low-standard dose

Primaquine (3.5mg x 7d)

Eligibility Criteria

• Age: 6 Months - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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;
• 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;

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Fundação de Medicina Tropical Dr. Heitor Vieira Dourado: lead
• Bill and Melinda Gates Foundation: collaborator
• Conselho Nacional de Desenvolvimento Científico e Tecnológico: collaborator

Study Sites (2)

Universidade Federal do Acre

Cruzeiro do Sul, Acre, Brazil

Location

Fundação de Medicina Tropical Doutor Heitor Vieira Dourado

Manaus, Amazonas, 69040-000, Brazil

Location

Related Publications (1)

• 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. doi: 10.1186/s12936-025-05686-y. Online ahead of print.

  PMID: 41430686 DERIVED

MeSH Terms

Conditions

Malaria, Vivax

Interventions

Primaquine

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Maria das Graças C Alecrim, PhD, MD

  Fundação de Medicina Tropical - HVD

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2021
• First Posted: September 16, 2021
• Study Start: August 26, 2021
• Primary Completion: July 29, 2024
• Study Completion: January 7, 2025
• Last Updated: February 20, 2025

Record last verified: 2025-02

Locations

BR (2)