Evaluation of the efficacy and safety of primaquine for clearance of gametocytes in uncomplicated falciparum malaria: a randomised clinical trial

There is evidence that falciparum malaria prevalence is decreasing in many countries and elimination rather than control is a consideration. Gametocytocidal therapy is likely to assume importance in achieving this goal, by reducing the transmission of parasites from humans to mosquitoes. Following effective treatment of harmful asexual parasites in humans, residual viable gametocytes are an infectious reservoir, enabling onward transmission of the parasite to mosquitoes. Artemisinins, the first line anti-malarials recommended by the WHO have some gametocytocidal action, but mosquito feeding experiments demonstrate that it is incomplete. Even submicroscopic gametocytaemias post treatment can cause infection in mosquitoes. Primaquine has potent gametocytocidal action. Its use is uncommon, given the risk of haemolytic anaemia in the context of G6PD deficiency, a polymorphism conserved in malaria endemic countries. This effect is dose-related. The WHO advocates the use of a single dose of primaquine to block transmission to mosquitoes, but there are currently insufficient pharmacokinetic and safety data on which to base this recommendation.

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Prevention

Intervention: Drug: Primaquine

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).

Other Name: primaquine phosphate

Study arm: 

• Placebo Comparator: Placebo

  Non-active drug

  Intervention: Drug: Primaquine

• Experimental: Low dose primaquine (PQ1)

  Lowest experimental dose of primaquine base: 0.1mg/kg

  Intervention: Drug: Primaquine

• Experimental: Intermediate dose primaquine (PQ2)

  Intermediate experimental dose of primaquine base: 0.4mg/kg

  Intervention: Drug: Primaquine

• Active Comparator: Reference dose primaquine (PQ-R)

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

  Intervention: Drug: Primaquine

Eligibility criteria:

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

ClinicalTrials.gov - NCT01365598Wellcome Trust awarded grant details

Drug-based Strategies

Oct 2009 — Oct 2013

$618,459

Uganda