High daily dose Short COurse PrimaquinE after G6PD testing for the radical cure of Plasmodium vivax malaria in Indonesia and Papua New Guinea: the SCOPE implementation study protocol.

BACKGROUND: Plasmodium vivax malaria remains an important threat to the public in the Asia Pacific region. Preventing P. vivax relapses is crucial for reducing morbidity from malaria and ultimately controlling and eliminating this species. Primaquine is the only widely available drug with antirelapse activity against dormant stages of P. vivax. Its widespread use in clinical practice is limited by its potential to cause severe haemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. METHODS: The primary aims of this staged, binational, multicentre, before-and-after implementation study are to determine the safety, feasibility, and cost-effectiveness of a revised package of case management interventions for improved P. vivax radical cure. The interventions include: i) pre-treatment testing of patients for G6PD deficiency using a semi-quantitative point-of-care device from SDBiosensor (ROK); ii) prescription of high dose primaquine (7mg/kg total dose) either over 7 days for G6PD normal patients (≥ 70% activity) or 14 days for intermediate patients (30- < 70% activity), or lower dose weekly primaquine over 8 weeks for deficient patients (< 30% activity); iii) improved patient education processes; iv) routine community-based review on day 3 (and day 7 for Stage 1) and v) enhanced malariometric surveillance and community pharmacovigilance. Stage 1 of the study (800 patients) will be implemented at 4 community clinics across Indonesia and Papua New Guinea (PNG) and will focus on analysis of treatment safety. If safety of the intervention is confirmed during Stage 1, the study will proceed to Stage 2, in which patient recruitment will be expanded to 10 clinics across Indonesia and PNG, and the feasibility of the similar intervention package will be assessed, but with a single community-based review on day 3. Stage 2 will run for 12 months and recruit approximately 11,410 patients. Mixed methods analyses of Stage 2 data will focus on the operational feasibility and cost-effectiveness of the revised case management package, with effectiveness determined through analysis of individual-level risk of P. vivax recurrence and population-level changes in incidence (with comparison to the pre-implementation period). Feasibility will be assessed via qualitative observations, in-depth interviews and focus groups of health care workers and participants. DISCUSSION: The intervention package will provide critical information on the safety, feasibility and cost-effectiveness of achieving radical cure with G6PD testing prior to high dose primaquine treatment and community-based follow-up. The study results will inform national malaria programs aiming to eliminate P. vivax in Indonesia and PNG by 2030. TRIAL REGISTRATION: The study was registered on clinicaltrials.gov for Indonesia: NCT05879224 on the 18th May 2023 and PNG: NCT05874271 on the 16th May 2023.