Evaluation of the Gametocytocidal Efficacy and Safety of Primaquine in Uncomplicated Falciparum Malaria in Uganda
- Registration Number
- NCT01365598
- Lead Sponsor
- London School of Hygiene and Tropical Medicine
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 468
- Age >/= 1 year and </= 10 years
- Weight over 10kg
- Fever >38 degrees C (tympanic) or history of fever in the last 24 hours
- P. falciparum parasitaemia <500 000/µl
- Normal G6PD enzyme function
- Enrolled in another study
- Evidence of severe illness/ danger signs
- Known allergy to study medications
- Haemoglobin < 8g/dL)
- Started menstruation
- Pregnancy or breastfeeding
- Primaquine taken within the last 4 weeks
- Blood transfusion within the last 90 days
- Non-falciparum malaria co-infection
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Primaquine Non-active drug Low dose primaquine (PQ1) Primaquine Lowest experimental dose of primaquine base: 0.1mg/kg Reference dose primaquine (PQ-R) Primaquine WHO-recommended dose of primaquine base: 0.75mg/kg Intermediate dose primaquine (PQ2) Primaquine Intermediate experimental dose of primaquine base: 0.4mg/kg
- Primary Outcome Measures
Name Time Method Mean (+/- SD) maximal fall in Hb (g/dL) from enrollment to day 28 of follow-up 28 days Mean maximal greatest negative difference in Hb (measured by Hemocue®) from enrollment value per treatment arm over 28 days follow up
Mean number of days to gametocyte clearance (gametocyte clearance time, GCT) 14 days 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.
- Secondary Outcome Measures
Name Time Method Incidence of serious adverse events by sign, symptom, laboratory parameter and relationship to taking study drug 28 days Percentage (number) per treatment arm during days 0-28
Mean (+/- SD) area under the curve of gametocyte density per day during 14 days of follow-up 14 days 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
Requirement for blood transfusion 28 days Percentage of children receiving blood transfusion per treatment arm during days 0-28
Follow-up day of Hb nadir 28 days Mean day of follow up (day 0-28) per treatment arm of lowest Hb measurement (by Hemocue®)
Incidence of gastrointestinal symptoms after taking study drug 6 days Percentage (number) of children with gastrointestinal symptoms per treatment arm during days 2-7
Trial Locations
- Locations (1)
Walukuba Health Centre IV
🇺🇬Jinja, Eastern Region, Uganda