Evaluation of the Gametocytocidal Efficacy and Safety of Primaquine in Uncomplicated Falciparum Malaria in Uganda

London School of Hygiene and Tropical Medicine

Status and phase: Completed; Phase 3

Conditions: Falciparum Malaria

Treatments: Drug: Primaquine

Study type: Interventional

Funder types: Other

Identifiers

NCT01365598

PQPF912

Details and patient eligibility

About

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.

Full 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.

Enrollment: 468 patients

Sex: All

Ages: 1 to 10 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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468 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Non-active drug

Treatment:

Drug: Primaquine

Low dose primaquine (PQ1)

Experimental group

Description:

Lowest experimental dose of primaquine base: 0.1mg/kg

Treatment:

Drug: Primaquine

Intermediate dose primaquine (PQ2)

Experimental group

Description:

Intermediate experimental dose of primaquine base: 0.4mg/kg

Treatment:

Drug: Primaquine

Reference dose primaquine (PQ-R)

Active Comparator group

Description:

WHO-recommended dose of primaquine base: 0.75mg/kg

Treatment:

Drug: Primaquine