Responsible investigator: Prof J. Kevin Baird
Funded by Medical Research Council/Wellcome Trust/UKAID Joint Global Health Trials
Plasmodium vivax malaria is a major cause of morbidity and now recognised as an important contributor to mortality in endemic areas. Recent evidence showed that P. vivax documented as harmful as P. falciparum, often turns severe and life-threatening with case fatality rate of 25% vs. 23% (P = 0.771) in Jayapura district of Papua. Shorter courses of higher daily doses of primaquine have the potential to improve adherence and thus effectiveness without compromising efficacy. Primaquine also has relatively weak but clinically relevant asexual stage activity against P. vivax so larger daily doses may substantially augment chloroquine’s blood stage activity at low levels of resistance. In Thailand directly observed primaquine (1mg/kg/day) administered over 7 days was well tolerated and reduced relapses by day 28 to 4%. This is encouraging but not definitive since many relapses present after one month. Longer follow-up is needed to distinguish whether relapse was prevented or deferred. If the efficacy, tolerability and safety of short-course, high-dose primaquine regimens can be assured across the range of endemic settings, along with reliable point-of-care G6PDd diagnostics, then this new primaquine regimen would be a major advance in malaria treatment improving adherence to and thus the effectiveness of anti-relapse therapy.
The study has the following objectives: 1) To determine whether a 7-day primaquine regimen is safe and not inferior to the standard 14-day regimen (total dose of 7mg/kg in both arms) in preventing P. vivax relapse in G6PD normal patients, 2) To assess the absolute risks and benefits of radical treatment regimens in different endemic settings., 3) To provide data on the safety of a weekly dose of primaquine (0.75 mg base/kg) in patients with G6PD deficiency dan 4) To identify the most cost-effective strategies for the management of P. vivax with respect to the use of G6PD tests, the dosing schedule and the epidemiological context.
This study will test the safety and efficacy of high dose-short course primaquine in G6PD normal patients. In a parallel single arm study we will also gather safety data on the use of weekly primaquine in patients with G6PDd.
A better understanding of the risks and benefits of primaquine is crucial in persuading policy makers and clinicians of the importance of the radical cure of vivax malaria that will reduce the parasite reservoir and decrease transmission. Our proposed multicentre randomised clinical trial will provide evidence across a variety of endemic settings on the safety and efficacy of high dose-short course primaquine in G6PD normal patients. In a parallel single arm study we will also gather safety data on the use of weekly primaquine in patients with G6PDd. Our study aims to generate evidence that will directly inform global public health policy for the radical cure of P. vivax.