Short Course Primaquine for the Radical Cure of P. Vivax Malaria - Indonesia

Vivax Malaria Clinical Trial

— SCOPE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05879224
• Other study ID #: MMV_PQ_21_01 U1111-1291-3218
• Status: Recruiting
• Phase: N/A
• Start date: August 7, 2023
• Est. completion date: July 31, 2025

Study information

• Verified date: February 2024
• Source: Menzies School of Health Research
• Contact: Vanessa Sakalidis, PhD
• Phone: +614 08 8946 8600
• Email: vanessa.sakalidis[@]menzies.edu.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The proportion of malaria that is the Plasmodium vivax species is increasing in Indonesia. Reducing vivax malaria will require innovative solutions to cure both the blood and liver stages of the disease. This study will evaluate of the feasibility of implementing point-of-care glucose-6-phosphate dehydrogenase deficiency (G6PD) testing. This will be followed by high dose, short course primaquine treatment regimens for patients with vivax malaria, and combined with patient education, surveillance, and pharmacovigilance. We plan to implement the study at 6 health facilities across Indonesia using a staged before-and-after study, with a mixed method evaluation.

Description:

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 allow 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 Indonesian Ministry 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 vivax malaria. These interventions are 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 six sites in Indonesia; four in Papua, one in North Sumatra and one in Lampung. We will use a staged approach for the implementation of the revised case management strategy, including patient education and counselling,community-based clinical review, with mixed methods evaluation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 11250
• Est. completion date: July 31, 2025
• Est. primary completion date: May 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months and older

Eligibility

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

Related Conditions & MeSH terms

• G6PD Deficiency
• Glucosephosphate Dehydrogenase Deficiency
• Malaria
• Malaria, Vivax
• Vivax Malaria

Intervention

Combination Product:
• Revised case management package
Point-of-care quantitative G6PD testing using G6PDSTANDARD (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 percent PQ14 (0.5 mg/kg/day for 14 days) if G6PDactivity is 30-70 percent PQ8w (0.75 mg/kg/week for 8 weeks) if G6DPactivity less than 30 percent Participant counselling at the health facility (Day 0): Supervision of first dose of primaquine Education regarding the 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

Locations

Country	Name	City	State
Indonesia	Puskesmas Hanura	Hanura	Lampung
Indonesia	Puskesmas Tanjung Leidong	Labuhanbatu	North Sumatra
Indonesia	Puskesmas Bhintuka	Mimika	Papua
Indonesia	Puskesmas Pasar Sentral	Mimika	Papua
Indonesia	Puskesmas Timika	Mimika	Papua
Indonesia	Puskesmas Wania	Mimika	Papua

Sponsors (13)

Lead Sponsor	Collaborator
Menzies School of Health Research	Burnet Institute, Gadjah Mada University, Indonesia University, Indonesian National Malaria Control Program, Ministry of Health, Institute of Tropical Medicine, Belgium, Medicines for Malaria Venture, National Research and Innovation Agency of Indonesia, PATH, UNITAID, Universitas Sumatera Utara, University of Melbourne, Yayasan Pengembangan Kesehatan dan Masyarakat

Country where clinical trial is conducted

Indonesia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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) ]
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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) ]
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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 7clinical review data	1 week
Secondary	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
Secondary	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
Secondary	Proportion of patients receiving a SD Biosensor G6PD test	The outcome will be assessed from patients' enrolment data	1 day
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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	Day 3
Secondary	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
Secondary	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=200patients (per facility) after implementation	18 months
Secondary	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
Secondary	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
Secondary	Household costs per P. vivax episode	This will be assessed from a household cost survey on a subset of patients	3 days
Secondary	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
Secondary	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
Secondary	Cost per component of the revised case management package	This will be assessed from health system data collected throughout the study	18 months
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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