Clinical trial NCT05874271: Short Course Primaquine for the Radical Cure of P. Vivax - Papua New Guinea
Official title: Feasibility of High Daily Dose Short Course Primaquine After G6PD Testing for the Radical Cure of Plasmodium Vivax Malaria
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Vivax Malaria
G6PD Deficiency
Keywords: primaquine
Lead sponsor: Macfarlane Burnet Institute for Medical Research and Public Health Ltd
Sponsor class: OTHER
Collaborators: name: Papua New Guinea Institute of Medical Research
name: Papua New Guinea National Department of Health
name: Menzies School of Health Research
name: University of Melbourne
name: Medicines for Malaria Venture
name: PATH
name: UNITAID
First posted: 2023-05-24
Enrollment: 5850
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.


Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patients experiencing at least one Serious Adverse Event (SAE) during treatment.
timeFrame: During treatment (up to 8 weeks)
measure: Proportion of patients experiencing at least one Adverse Event of Special Interest (AESI) during treatment.
timeFrame: During treatment (up to 8 weeks)
measure: Proportion of patients with P. vivax malaria who correctly receive all components of the revised case management package
timeFrame: 3 days
Secondary outcomes:
measure: The proportion of patients with any AESI during treatment
timeFrame: During treatment (up to 8 weeks)
measure: The proportion of patients with a gastrointestinal (GI) AESI during treatment
timeFrame: During treatment (up to 8 weeks)
measure: The proportion of patients with an AESI related to haemolysis during treatment
timeFrame: During treatment (up to 8 weeks)
measure: The proportion of patients an AESI related to methaemoglobinaemia
timeFrame: During treatment (up to 8 weeks)
measure: Proportion of patients permanently stopping PQ before end of treatment
timeFrame: During treatment (up to 8 weeks)
measure: The proportion of patients receiving correct treatment based on G6PD activity
timeFrame: 1 day
measure: Proportion of patients who were reviewed on Day 3 and Day 7
timeFrame: 1 week
measure: Perception of and experience with new radical cure tools among health care providers and community members
timeFrame: 6 months
measure: Proportion of health care practitioners who comply with the revised radical cure treatment algorithm
timeFrame: 1 day
measure: Proportion of patients receiving a SD Biosensor G6PD test
timeFrame: 1 day
measure: Proportion of eligible P. vivax malaria patients receiving the correct dose of primaquine based on the result of the G6PD test
timeFrame: 1 day
measure: 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)
timeFrame: 1 day
measure: Proportion of P. vivax malaria patients that are reviewed on Day 3
timeFrame: 3 days
measure: Proportion of P. vivax malaria patients that adhere to their prescribed primaquine regimen
timeFrame: 3 days
measure: Factors influencing acceptability and feasibility of the new radical cure tools among health care providers are identified
timeFrame: 3 days
measure: Barriers and enablers of uptake and implementation at the sub-national levels are identified
timeFrame: 18 months
measure: Factors influencing compliance with G6PD testing and perceptions of new drug regimens and serious adverse events among health care providers are identified
timeFrame: 18 months
measure: Required knowledge, skills, and training to administer the revised case management and patient-counselling identified
timeFrame: 18 months
measure: Factors influencing the barriers and facilitators to patient adherence to primaquine after the rollout of the revised case management identified
timeFrame: 18 months
measure: Factors influencing the acceptability and feasibility of community-based clinical review at Day 3 of primaquine treatment identified.
timeFrame: 18 months
measure: Perceptions of the new radical cure tools and serious adverse events at the community level identified
timeFrame: 18 months
measure: Local acceptability of the revised case management algorithms among patients, their families, and healthcare workers established
timeFrame: 18 months
measure: The monthly incidence of confirmed symptomatic P. vivax malaria episodes (mono-infection or mixed) before implementation versus after implementation
timeFrame: 18 months
measure: The prevalence of P. vivax parasitaemia in patients presenting with fever before implementation versus after implementation
timeFrame: 18 months
measure: Cumulative risk of representation to the same clinic with symptomatic P. vivax malaria within 6 months
timeFrame: 18 months
measure: Costs of implementing policy from a healthcare provider perspective, including health systems strengthening processes
timeFrame: 18 months
measure: Household costs per P. vivax episode
timeFrame: 3 days
measure: Overall cost-effectiveness of changing policy if revised case management is effective
timeFrame: 18 months
measure: Cost per episode of P. vivax malaria from the healthcare provider and societal perspectives
timeFrame: 18 months
measure: Cost per component of the revised case management package
timeFrame: 18 months
measure: 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
timeFrame: 18 months
measure: 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)
timeFrame: 3 days
measure: Number of patients with an SAE who are identified by community or clinic staff follow-up and referred to hospital for further management
timeFrame: During treatment (up to 8 weeks)
measure: The proportion of patients eligible to receive PQ who had a SAE during treatment
timeFrame: During treatment (up to 8 weeks)
measure: Prevalence of severe anaemia in patients presenting with fever before and after implementation
timeFrame: 18 months
Other outcomes:
Locations:
city: Kokopo
country: Papua New Guinea
facility: Napapar Health Centre
state: East New Britain
city: Wewak
country: Papua New Guinea
facility: Wirui Clinic
state: East Sepik
city: Vanimo
country: Papua New Guinea
facility: Baro Clinic
state: West Sepik
city: Madang
country: Papua New Guinea
facility: Mugil Health Centre
Study officials:
affiliation: Papua New Guinea Institute of Medical Research
name: Moses Laman, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Macfarlane Burnet Institute for Medical Research and Public Health
name: Leanne Robinson, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Papua New Guinea National Department of Health
name: Leo Makita
role: PRINCIPAL_INVESTIGATOR
affiliation: Papua New Guinea Institute of Medical Research
name: William Pomat, Prof
role: PRINCIPAL_INVESTIGATOR
References: