Clinical trial NCT05879224: Short Course Primaquine for the Radical Cure of P. Vivax Malaria - Indonesia
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: Menzies School of Health Research
Sponsor class: OTHER
Collaborators: name: Gadjah Mada University
name: Universitas Sumatera Utara
name: Indonesia University
name: Yayasan Pengembangan Kesehatan dan Masyarakat
name: Indonesian National Malaria Control Program, Ministry of Health
name: National Research and Innovation Agency of Indonesia
name: Burnet Institute
name: University of Melbourne
name: Medicines for Malaria Venture
name: PATH
name: UNITAID
name: Institute of Tropical Medicine, Belgium
First posted: 2023-05-30
Enrollment: 11250
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Combination Product: Revised case management package
Primary purpose: OTHER

Brief 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.

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.

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: Day 3
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: Hanura
country: Indonesia
facility: Puskesmas Hanura
state: Lampung
city: Labuhanbatu
country: Indonesia
facility: Puskesmas Tanjung Leidong
state: North Sumatra
city: Mimika
country: Indonesia
facility: Puskesmas Bhintuka
state: Papua
city: Mimika
country: Indonesia
facility: Puskesmas Pasar Sentral
state: Papua
city: Mimika
country: Indonesia
facility: Puskesmas Timika
state: Papua
city: Mimika
country: Indonesia
facility: Puskesmas Wania
state: Papua
Study officials:
affiliation: Menzies School of Health Research
name: Ric Price, MD
role: PRINCIPAL_INVESTIGATOR
References: