The purpose of this study is to evaluate the safety and efficacy of lower doses of primaquine compared to the dose recommended by the WHO for reducing P. falciparum gametocytes in the infected human host to prevent transmission of falciparum malaria to the anopheles mosquito vector.
A single dose of 0.75mg/kg primaquine base is recommended by the WHO to block transmission of falciparum malaria from infected humans to mosquitoes by clearing gametocytes. However, the optimal dose for safety and efficacy has not been evaluated. Dose-finding data is important because primaquine has a dose-dependent risk of causing haemolysis (destruction of blood cells) in pre-disposed individuals, such as those with G6PD deficiency. G6PD deficiency is most prevalent in malaria-endemic areas. Therefore, it is essential that data on primaquine's safety is available in such areas. The investigators hypothesise that lower doses of primaquine have a lower risk of adverse effects compared to the WHO-recommended dose, but retain the transmission-blocking efficacy. The investigators propose to test this hypothesis in a four-arm clinical trial with a non-inferiority design to evaluate the efficacy and a superiority design to evaluate the safety of the WHO dose (0.75mg/kg) and lower doses of primaquine for clearance of P. falciparum gametocytes in children in Uganda. The study will include a pharmacokinetic analysis.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
468
Single dose of oral primaquine phosphate. Comparator dose is 0.75mg/kg primaquine base. Each experimental arm is a different (reduced) dose of primaquine phosphate. Placebo contains no primaquine phosphate (non-active ingredients only).
Walukuba Health Centre IV
Jinja, Eastern Region, Uganda
Mean number of days to gametocyte clearance (gametocyte clearance time, GCT)
Mean number of days per treatment arm for gametocytes to become undetectable using sub-microscopic molecular testing methods (real-time nucleic acid sequence-based amplification, QT-NASBA)and interpolated from measured data points.
Time frame: 14 days
Mean (+/- SD) maximal fall in Hb (g/dL) from enrollment to day 28 of follow-up
Mean maximal greatest negative difference in Hb (measured by Hemocue®) from enrollment value per treatment arm over 28 days follow up
Time frame: 28 days
Mean (+/- SD) area under the curve of gametocyte density per day during 14 days of follow-up
An estimate of the area under the curve of gametocytes (measured by QT-NASBA) seen over time, averaged per day of follow up (days 0-14) and interpolated from measured data points
Time frame: 14 days
Requirement for blood transfusion
Percentage of children receiving blood transfusion per treatment arm during days 0-28
Time frame: 28 days
Follow-up day of Hb nadir
Mean day of follow up (day 0-28) per treatment arm of lowest Hb measurement (by Hemocue®)
Time frame: 28 days
Incidence of serious adverse events by sign, symptom, laboratory parameter and relationship to taking study drug
Percentage (number) per treatment arm during days 0-28
Time frame: 28 days
Incidence of gastrointestinal symptoms after taking study drug
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Percentage (number) of children with gastrointestinal symptoms per treatment arm during days 2-7
Time frame: 6 days