Short Course Primaquine for the Radical Cure of P. Vivax - Papua New Guinea
- Conditions
- Vivax MalariaG6PD Deficiency
- Interventions
- Combination Product: Revised case management package
- Registration Number
- NCT05874271
- Lead Sponsor
- Macfarlane Burnet Institute for Medical Research and Public Health Ltd
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 5850
- Patients with vivax malaria
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Revised case management package Revised case management package -
- Primary Outcome Measures
Name Time Method Proportion of patients experiencing at least one Serious Adverse Event (SAE) during treatment. During treatment (up to 8 weeks) SAEs are collected during clinical review using a study-specific questionnaire
Proportion of patients experiencing at least one Adverse Event of Special Interest (AESI) during treatment. During treatment (up to 8 weeks) AESIs (haemolysis, methaemoglobinaemia and gastrointestinal discomfort) are collected during clinical review using a study-specific questionnaire
Proportion of patients with P. vivax malaria who correctly receive all components of the revised case management package 3 days 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
- Secondary Outcome Measures
Name Time Method Factors influencing compliance with G6PD testing and perceptions of new drug regimens and serious adverse events among health care providers are identified 18 months This will be assessed using stakeholder interviews and focus groups
Proportion of patients permanently stopping PQ before end of treatment During treatment (up to 8 weeks) Discontinuation of PQ will be assessed using a study-specific questionnaire
Proportion of patients who were reviewed on Day 3 and Day 7 1 week This will be assessed by linking patients enrolment data with Day 3 and Day 7 clinical review data
The proportion of patients with an AESI related to haemolysis during treatment During treatment (up to 8 weeks) AESIs are collected during clinical review using a study-specific questionnaire
Proportion of patients receiving a SD Biosensor G6PD test 1 day The outcome will be assessed from patients' enrolment data
Proportion of eligible P. vivax malaria patients receiving the correct dose of primaquine based on the result of the G6PD test 1 day The outcome will be assessed from patients' enrolment data
The proportion of patients with any AESI during treatment During treatment (up to 8 weeks) AESIs are collected during clinical review using a study-specific questionnaire
The proportion of patients with a gastrointestinal (GI) AESI during treatment During treatment (up to 8 weeks) AESIs are collected during clinical review using a study-specific questionnaire
The proportion of patients an AESI related to methaemoglobinaemia During treatment (up to 8 weeks) AESIs are collected during clinical review using a study-specific questionnaire
Perception of and experience with new radical cure tools among health care providers and community members 6 months This will be assessed using stakeholder interviews
The proportion of patients receiving correct treatment based on G6PD activity 1 day This will be assessed by linking patients G6PD activity results measured during study enrolment with primaquine dose prescribed on the same day
Proportion of health care practitioners who comply with the revised radical cure treatment algorithm 1 day The outcome will be assessed from patients' enrolment data
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) 1 day The outcome will be assessed from patients' enrolment data
Proportion of P. vivax malaria patients that are reviewed on Day 3 3 days This will be assessed by linking patients' enrolment data with clinical review data
Proportion of P. vivax malaria patients that adhere to their prescribed primaquine regimen 3 days This will be assessed by linking patients' enrolment data with clinical review data
Barriers and enablers of uptake and implementation at the sub-national levels are identified 18 months This will be assessed using stakeholder interviews and focus groups
Factors influencing the acceptability and feasibility of community-based clinical review at Day 3 of primaquine treatment identified. 18 months This will be assessed using stakeholder interviews and focus groups
Factors influencing acceptability and feasibility of the new radical cure tools among health care providers are identified 3 days This will be assessed using stakeholder interviews, observations and focus groups
Required knowledge, skills, and training to administer the revised case management and patient-counselling identified 18 months This will be assessed using stakeholder interviews and focus groups
Factors influencing the barriers and facilitators to patient adherence to primaquine after the rollout of the revised case management identified 18 months This will be assessed using stakeholder interviews and focus groups
Perceptions of the new radical cure tools and serious adverse events at the community level identified 18 months This will be assessed using stakeholder interviews and focus groups
Local acceptability of the revised case management algorithms among patients, their families, and healthcare workers established 18 months This will be assessed using stakeholder interviews and focus groups
Cost per component of the revised case management package 18 months This will be assessed from health system data collected throughout the study
The proportion of patients eligible to receive PQ who had a SAE during treatment During treatment (up to 8 weeks) This will be assessed by linking enrolment data, clinical review, study specific questionnaire and SAE form
The monthly incidence of confirmed symptomatic P. vivax malaria episodes (mono-infection or mixed) before implementation versus after implementation 18 months This will be assessed by comparing facility surveillance data before implementation with facility surveillance data after implementation
The prevalence of P. vivax parasitaemia in patients presenting with fever before implementation versus after implementation 18 months 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
Cumulative risk of representation to the same clinic with symptomatic P. vivax malaria within 6 months 18 months This will be assessed by linking patients' enrolment data
Household costs per P. vivax episode 3 days This will be assessed from a household cost survey on a subset of patients
Overall cost-effectiveness of changing policy if revised case management is effective 18 months This will be assessed from health system data collected throughout the study
Cost per episode of P. vivax malaria from the healthcare provider and societal perspectives 18 months This will be assessed from health system data collected throughout the study
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 18 months This will be assessed from health system data collected throughout the study
Costs of implementing policy from a healthcare provider perspective, including health systems strengthening processes 18 months This will be assessed from health system data collected throughout the study
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) 3 days This will be assessed from clinical review data and study-specific questionnaire
Number of patients with an SAE who are identified by community or clinic staff follow-up and referred to hospital for further management During treatment (up to 8 weeks) This will be assessed by linking clinical review data, study specific questionnaire and SAE form
Prevalence of severe anaemia in patients presenting with fever before and after implementation 18 months This will be assessed by comparing the facility surveillance data before implementation with facility surveillance data after implementation
Trial Locations
- Locations (4)
Wirui Clinic
🇵🇬Wewak, East Sepik, Papua New Guinea
Napapar Health Centre
🇵🇬Kokopo, East New Britain, Papua New Guinea
Baro Clinic
🇵🇬Vanimo, West Sepik, Papua New Guinea
Mugil Health Centre
🇵🇬Madang, Papua New Guinea