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

February 1, 2024 updated by: Menzies School of Health Research

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

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.

Study Overview

Status

Recruiting

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

11250

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Lampung
      • Hanura, Lampung, Indonesia
        • Recruiting
        • Puskesmas Hanura
        • Contact:
        • Principal Investigator:
          • Inge Sutanto, MD
    • North Sumatra
      • Labuhanbatu, North Sumatra, Indonesia
        • Recruiting
        • Puskesmas Tanjung Leidong
        • Contact:
        • Principal Investigator:
          • Ayodhia Pasaribu, MD
    • Papua
      • Mimika, Papua, Indonesia
        • Recruiting
        • Puskesmas Bhintuka
        • Contact:
        • Principal Investigator:
          • Jeanne R Poespoprodjo, MD
      • Mimika, Papua, Indonesia
        • Recruiting
        • Puskesmas Pasar Sentral
        • Contact:
        • Principal Investigator:
          • Jeanne R Poespoprodjo, MD
      • Mimika, Papua, Indonesia
        • Recruiting
        • Puskesmas Timika
        • Contact:
        • Principal Investigator:
          • Jeanne R Poespoprodjo, MD
      • Mimika, Papua, Indonesia
        • Recruiting
        • Puskesmas Wania
        • Contact:
        • Principal Investigator:
          • Jeanne R Poespoprodjo, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Revised case management package
  1. Point-of-care quantitative G6PD testing using G6PDSTANDARD (SD Biosensor) prior to use of primaquine (Day 0)
  2. 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
  3. 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
  4. 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
  5. 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 with P. vivax malaria who correctly receive all components of the revised case management package
Time Frame: 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
3 days
Proportion of patients experiencing at least one Serious Adverse Event (SAE) during treatment
Time Frame: During treatment (up to 8 weeks) ]
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
Time Frame: During treatment (up to 8 weeks)
AESIs (haemolysis, methaemoglobinaemia and gastrointestinal discomfort) are collected during clinical review using a study-specific questionnaire
During treatment (up to 8 weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The proportion of patients with any AESI during treatment
Time Frame: During treatment (up to 8 weeks)
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
Time Frame: During treatment (up to 8 weeks)
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
Time Frame: During treatment (up to 8 weeks)
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
Time Frame: During treatment (up to 8 weeks)
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
Time Frame: 1 day
This will be assessed by linking patients G6PD activity results measured during study enrolment with primaquine dose prescribed on the same day
1 day
Perception of and experience with new radical cure tools among health care providers and community members
Time Frame: 6 months
This will be assessed using stakeholder interviews
6 months
Proportion of health care practitioners who comply with the revised radical cure treatment algorithm
Time Frame: 1 day
The outcome will be assessed from patients' enrolment data
1 day
Proportion of patients receiving a SD Biosensor G6PD test
Time Frame: 1 day
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
Time Frame: 1 day
The outcome will be assessed from patients' enrolment data
1 day
Proportion of P. vivax malaria patients that are reviewed on Day 3
Time Frame: 3 days
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
Time Frame: 3 days
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
Time Frame: 3 days
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
Time Frame: 18 months
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
Time Frame: 18 months
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
Time Frame: 18 months
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
Time Frame: 18 months
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
Time Frame: 18 months
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
Time Frame: 18 months
This will be assessed by comparing facility surveillance data before implementation with facility surveillance data after implementation
18 months
Cumulative risk of representation to the same clinic with symptomatic P. vivax malaria within 6 months
Time Frame: 18 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
Time Frame: 18 months
This will be assessed from health system data collected throughout the study
18 months
Household costs per P. vivax episode
Time Frame: 3 days
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
Time Frame: 18 months
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
Time Frame: 18 months
This will be assessed from health system data collected throughout the study
18 months
Cost per component of the revised case management package
Time Frame: 18 months
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
Time Frame: 18 months
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)
Time Frame: 3 days
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
Time Frame: During treatment (up to 8 weeks)
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
Time Frame: During treatment (up to 8 weeks)
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
Time Frame: 18 months
This will be assessed by comparing the facility surveillance data before implementation with facility surveillance data after implementation
18 months
The proportion of patients with an AESI related to haemolysis during treatment
Time Frame: During treatment (up to 8 weeks) ]
AESIs are collected during clinical review using a study-specific questionnaire
During treatment (up to 8 weeks) ]
Proportion of patients who were reviewed on Day 3 and Day 7
Time Frame: 1 week
This will be assessed by linking patients enrolment data with Day 3 and Day 7clinical review data
1 week
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
Time Frame: 1 day
The outcome will be assessed from patients' enrolment data
1 day
Factors influencing the acceptability and feasibility of community-based clinical review at Day 3 of primaquine treatment identified
Time Frame: 18 months
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
Time Frame: Day 3
This will be assessed using stakeholder interviews and focus groups
Day 3
The prevalence of P. vivax parasitaemia in patients presenting with fever before implementation versus after implementation
Time Frame: 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=200patients (per facility) after implementation
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 7, 2023

Primary Completion (Estimated)

May 31, 2025

Study Completion (Estimated)

July 31, 2025

Study Registration Dates

First Submitted

May 18, 2023

First Submitted That Met QC Criteria

May 18, 2023

First Posted (Actual)

May 30, 2023

Study Record Updates

Last Update Posted (Actual)

February 5, 2024

Last Update Submitted That Met QC Criteria

February 1, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

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 Requests can be submitted to Professor Ric Price, Menzies School of Health Research, Email:ric.price@menzies.edu.au and Dr Jeanne Rini Poespoprodjo, Universitas Gadjah Mada, Email:didot2266@yahoo.com

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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