A multicentre randomised, placebo-controlled comparison of short and long course primaquine regimens (IMPROV)

 

Aim:

This clinical trial assessed the efficacy and safety of a short-course high dose primaquine regimen for the radical cure of vivax malaria. 

Rationale:

Outside of sub-Saharan Africa, malaria is caused by two main parasites: Plasmodium falciparum and Plasmodium vivax. P. vivax forms dormant liver stages that reactivate weeks or months following an acute infection and can lead to severe or life-threatening disease. The WHO currently recommends a treatment with 14 days of primaquine to kill the liver stage parasites, but the long course of treatment means that many patients don’t complete their medication and fail treatment.

This large clinical trial enrolled 2388 patients at eight sites and treated them with high dose primaquine (total dose 7mg/kg) administered either over 14-days (0.5mg/kg/day) or 7 days (1mg/kg/day). Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, an inherited disorder found in up to 20% of some populations, are at risk of drug-induced haemolysis which causes severe anaemia. All patients were tested for G6PD before being treated.

Our research has found:

In G6PD normal patients, the 7-day primaquine regimen was well tolerated and non-inferior to 14-day primaquine. In all sites, both primaquine regimens had almost 90% cure rates compared to a relapse rate of 50% in patients not treated with primaquine.

Implications for policy and practice:

The findings have important implications for the treatment and elimination of vivax malaria in the Asia-Pacific, the Horn of Africa and the Americas. The short-course regimen has potential to improve adherence and therefore effectiveness of primaquine for the radical cure of P. vivax. A policy of testing for G6PD deficiency and treating with short-course high-dose primaquine is now being considered by several malaria endemic countries. Further studies are underway to study the safety and effectiveness of this regimen in clinical practice.

Our research locations:
  • Afghanistan
  • Indonesia 
  • Ethiopia
  • Vietnam.