Short Course Primaquine for the Radical Cure of P. Vivax - Papua New Guinea (SCOPE)

Feasibility of High Daily Dose Short Course Primaquine After G6PD Testing for the Radical Cure of Plasmodium Vivax Malaria

Significant gains have been made in reducing the overall burden of malaria worldwide, however these have been far greater for Plasmodium falciparum than P. vivax.

P. vivax remains a major obstacle to malaria control and elimination efforts, largely due to its ability to form dormant liver stages (hypnozoites) that allows it to escape detection and treatment. Importantly, they are susceptible only to 8 aminoquinolines such as primaquine. However, primaquine is associated with risk of haemolysis in individuals with a genetic condition, called glucose-6-phosphate dehydrogenase (G6PD) deficiency. Additionally, the recommended 14-day prolonged treatment regimen is associated with poor treatment adherence, hence ineffective primaquine treatment. Innovative solutions to the radical cure of both the blood and liver stages of P. vivax are urgently required.

The PNG National Department of Health has requested a pragmatic study of the feasibility and cost-effectiveness of implementing point-of-care G6PD testing followed by high-dose, short-course primaquine treatment regimens for patients with P. vivax malaria. This revised case management is to be combined with practicable enhancements to patient education, supervision, malariometric surveillance and pharmacovigilance.

This will be a before-after longitudinal health facility-based study implemented at Napapar and Mugil health centres and Baro and Wirui clinics. A staged approach for the implementation of the revised case management strategy will be used, including patient education and counselling, community-based clinical review, with mixed methods evaluation.

Study Overview

• Status: Completed
• Conditions: Vivax Malaria; G6PD Deficiency
• Intervention / Treatment: Combination product: Revised case management package

• Study Type: Interventional
• Enrollment (Actual): 794
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Papua New Guinea
  • East New Britain Province
    • Kokopo, East New Britain Province, Papua New Guinea
      • Napapar Health Centre
  • East Sepik Province
    • Wewak, East Sepik Province, Papua New Guinea
      • Wirui Clinic
  • Madang Province
    • Madang, Madang Province, Papua New Guinea
      • Mugil Health Centre
  • Sandaun Province
    • Vanimo, Sandaun Province, Papua New Guinea
      • Baro Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with vivax malaria

Exclusion Criteria:

• Patients who are pregnant
• Patients who are breastfeeding
• Patients with a Hb <8g/dL
• Patients with a previous adverse reaction to primaquine
• Patient with severe malaria

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Revised case management package

Combination product: Revised case management package; Point-of-care quantitative G6PD testing using G6PD STANDARD (SD Biosensor) prior to use of primaquine (Day 0); Prescription of short course primaquine (7 mg/kg total) (Day 0):PQ7 (1 mg/kg/day for 7 days) if G6PD activity greater than 70 percentPQ14 (0.5 mg/kg/day for 14 days) if G6PD activity is 30-70 percentPQ8w (0.75 mg/kg/week for 8 weeks) if G6DP activity less than 30 percent; Participant counselling at the health facility (Day 0):Supervision of first dose of primaquineEducation regarding importance and risks of primaquine therapy and necessity to take primaquine with food; Community based clinical review on Day 3 (and Day 7 for the first 300 participants) to detect and manage gastrointestinal or haemolytic adverse effects of treatment and encourage adherence to full treatment regime; Improved malariometric surveillance and pharmacovigilance to support wider scale use of the revised case management

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients experiencing at least one Serious Adverse Event (SAE) during treatment.	SAEs are collected during clinical review using a study-specific questionnaire	During treatment (up to 8 weeks)
Proportion of patients experiencing at least one Adverse Event of Special Interest (AESI) during treatment.	AESIs (haemolysis, methaemoglobinaemia and gastrointestinal discomfort) are collected during clinical review using a study-specific questionnaire	During treatment (up to 8 weeks)
Proportion of patients with P. vivax malaria who correctly receive all components of the revised case management package	Measured by completion of G6PD testing and the correct prescription of primaquine based on G6PD activity, completion of patients counselling and community based follow up on Day 3	3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients with any AESI during treatment	AESIs are collected during clinical review using a study-specific questionnaire	During treatment (up to 8 weeks)
The proportion of patients with a gastrointestinal (GI) AESI during treatment	AESIs are collected during clinical review using a study-specific questionnaire	During treatment (up to 8 weeks)
The proportion of patients with an AESI related to haemolysis during treatment	AESIs are collected during clinical review using a study-specific questionnaire	During treatment (up to 8 weeks)
The proportion of patients an AESI related to methaemoglobinaemia	AESIs are collected during clinical review using a study-specific questionnaire	During treatment (up to 8 weeks)
Proportion of patients permanently stopping PQ before end of treatment	Discontinuation of PQ will be assessed using a study-specific questionnaire	During treatment (up to 8 weeks)
The proportion of patients receiving correct treatment based on G6PD activity	This will be assessed by linking patients G6PD activity results measured during study enrolment with primaquine dose prescribed on the same day	1 day
Proportion of patients who were reviewed on Day 3 and Day 7	This will be assessed by linking patients enrolment data with Day 3 and Day 7 clinical review data	1 week
Perception of and experience with new radical cure tools among health care providers and community members	This will be assessed using stakeholder interviews	6 months
Proportion of health care practitioners who comply with the revised radical cure treatment algorithm	The outcome will be assessed from patients' enrolment data	1 day
Proportion of patients receiving a SD Biosensor G6PD test	The outcome will be assessed from patients' enrolment data	1 day
Proportion of eligible P. vivax malaria patients receiving the correct dose of primaquine based on the result of the G6PD test	The outcome will be assessed from patients' enrolment data	1 day
Proportion of P. vivax malaria patients who are ineligible for daily primaquine and are incorrectly given primaquine (including infants, pregnant females and G6PD deficient patients)	The outcome will be assessed from patients' enrolment data	1 day
Proportion of P. vivax malaria patients that are reviewed on Day 3	This will be assessed by linking patients' enrolment data with clinical review data	3 days
Proportion of P. vivax malaria patients that adhere to their prescribed primaquine regimen	This will be assessed by linking patients' enrolment data with clinical review data	3 days
Factors influencing acceptability and feasibility of the new radical cure tools among health care providers are identified	This will be assessed using stakeholder interviews, observations and focus groups	3 days
Barriers and enablers of uptake and implementation at the sub-national levels are identified	This will be assessed using stakeholder interviews and focus groups	18 months
Factors influencing compliance with G6PD testing and perceptions of new drug regimens and serious adverse events among health care providers are identified	This will be assessed using stakeholder interviews and focus groups	18 months
Required knowledge, skills, and training to administer the revised case management and patient-counselling identified	This will be assessed using stakeholder interviews and focus groups	18 months
Factors influencing the barriers and facilitators to patient adherence to primaquine after the rollout of the revised case management identified	This will be assessed using stakeholder interviews and focus groups	18 months
Factors influencing the acceptability and feasibility of community-based clinical review at Day 3 of primaquine treatment identified.	This will be assessed using stakeholder interviews and focus groups	18 months
Perceptions of the new radical cure tools and serious adverse events at the community level identified	This will be assessed using stakeholder interviews and focus groups	18 months
Local acceptability of the revised case management algorithms among patients, their families, and healthcare workers established	This will be assessed using stakeholder interviews and focus groups	18 months
The monthly incidence of confirmed symptomatic P. vivax malaria episodes (mono-infection or mixed) before implementation versus after implementation	This will be assessed by comparing facility surveillance data before implementation with facility surveillance data after implementation	18 months
The prevalence of P. vivax parasitaemia in patients presenting with fever before implementation versus after implementation	This will be assessed by comparing cross-sectional data on n=200 patients (per facility) collected before implementation to the prevalence collected in n=200 patients (per facility) after implementation	18 months
Cumulative risk of representation to the same clinic with symptomatic P. vivax malaria within 6 months	This will be assessed by linking patients' enrolment data	18 months
Costs of implementing policy from a healthcare provider perspective, including health systems strengthening processes	This will be assessed from health system data collected throughout the study	18 months
Household costs per P. vivax episode	This will be assessed from a household cost survey on a subset of patients	3 days
Overall cost-effectiveness of changing policy if revised case management is effective	This will be assessed from health system data collected throughout the study	18 months
Cost per episode of P. vivax malaria from the healthcare provider and societal perspectives	This will be assessed from health system data collected throughout the study	18 months
Cost per component of the revised case management package	This will be assessed from health system data collected throughout the study	18 months
If revised case management package is effective (significantly reduces the incidence of malaria), then the cost-effectiveness of implementing the revised case management as compared with usual care	This will be assessed from health system data collected throughout the study	18 months
Proportion of CHWs who correctly act on early signs of haemolytic anaemia and GI events (i.e. refer patients for further medical review, instruct patient to discontinue treatment)	This will be assessed from clinical review data and study-specific questionnaire	3 days
Number of patients with an SAE who are identified by community or clinic staff follow-up and referred to hospital for further management	This will be assessed by linking clinical review data, study specific questionnaire and SAE form	During treatment (up to 8 weeks)
The proportion of patients eligible to receive PQ who had a SAE during treatment	This will be assessed by linking enrolment data, clinical review, study specific questionnaire and SAE form	During treatment (up to 8 weeks)
Prevalence of severe anaemia in patients presenting with fever before and after implementation	This will be assessed by comparing the facility surveillance data before implementation with facility surveillance data after implementation	18 months

Collaborators and Investigators

• Sponsor: Macfarlane Burnet Institute for Medical Research and Public Health Ltd
• Collaborators: PATH; UNITAID; University of Melbourne; Menzies School of Health Research; Medicines for Malaria Venture; Papua New Guinea Institute of Medical Research; Papua New Guinea National Department of Health
• Investigators: Principal Investigator: Moses Laman, Dr, Papua New Guinea Institute of Medical Research; Principal Investigator: Leanne Robinson, Prof, Macfarlane Burnet Institute for Medical Research and Public Health; Principal Investigator: Leo Makita, Papua New Guinea National Department of Health; Principal Investigator: William Pomat, Prof, Papua New Guinea Institute of Medical Research

Publications and helpful links

General Publications

• SCOPE Study Group. 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. BMC Infect Dis. 2025 Jul 16;25(1):922. doi: 10.1186/s12879-025-11109-9.

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2023
• Primary Completion (Actual): October 25, 2025
• Study Completion (Actual): October 25, 2025

Study Registration Dates

• First Submitted: May 5, 2023
• First Submitted That Met QC Criteria: May 16, 2023
• First Posted (Actual): May 24, 2023

Study Record Updates

• Last Update Posted (Actual): December 5, 2025
• Last Update Submitted That Met QC Criteria: November 28, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: primaquine
• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Infections; Hematologic Diseases; Protozoan Infections; Parasitic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Carbohydrate Metabolism, Inborn Errors; Malaria; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hemic and Lymphatic Diseases; Malaria, Vivax; Glucosephosphate Dehydrogenase Deficiency
• Other Study ID Numbers: MMV_PQ_21_02; U1111-1285-4864 (Other Identifier: WHO Universal Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study Protocol and Statistical Analysis Plan will be made available to others. The results will be published in peer-reviewed open access journals and disseminated to stakeholders. De-identified quantitative data for the purposes of confirming risk of adverse events will be available to researchers who provide a methodological sound proposal that is in line with the aims of the approved protocol.
• IPD Sharing Access Criteria: Access is subject to approval by the SCOPE Data Access Committee to ensure that the use of data protects the interests of the participants and researchers according to the terms of ethics approval and principles of equitable data sharing. Requests can be submitted to the Burnet Institute and Papua New Guinea Institute of Medical Research email:evelien.rosens@burnet.edu.au / mary.malai@pngimr.org.pg
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No