Study to Evaluate Primaquine for Radical Cure of Uncomplicated Plasmodium Vivax Malaria in Children
Status:
Recruiting
Trial end date:
2022-12-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 2
Details
Lead Sponsor:
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
Collaborators:
Bill and Melinda Gates Foundation Conselho Nacional de Desenvolvimento Científico e Tecnológico