Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05879224
Other study ID # MMV_PQ_21_01 U1111-1291-3218
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
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
Health authority
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

Study Design


Related Conditions & MeSH terms


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
See also
  Status Clinical Trial Phase
Completed NCT01625871 - Artemether/Lumefantrine and Vivax Malaria Phase 3
Completed NCT02876549 - G6PD Assessment Before Primaquine for Radical Treatment of Vivax Malaria Phase 4
Completed NCT01218932 - Pharmacokinetic Study of Primaquine and Chloroquine in Healthy Subjects Phase 1
Recruiting NCT04228315 - Biomarkers of P. Vivax Relapse N/A
Completed NCT02118090 - Assessment of Plasmodium Vivax Chloroquine Resistance in Cambodia: Phase 4
Completed NCT01074905 - Study on the Treatment of Vivax Malaria Phase 3
Completed NCT04222088 - TES of Artemether-lumefantrine for Pf and Chloroquine for Pv in the Philippines From 2013-2014
Completed NCT01546961 - Chloroquine Population Pharmacokinetics in Pre and Post-partum Women N/A
Completed NCT00158548 - ACT With Chloroquine, Amodiaquine & Sulphadoxine-pyrimethamine in Pakistan Phase 3
Completed NCT00682578 - A Comparative Study of Artekin With Standard Malarial Treatment Regimes in Afghanistan Phase 3
Completed NCT00157833 - A Randomized Trial of Coartemether and Artekin for the Treatment of Uncomplicated Malaria in Papua, Indonesia. N/A
Active, not recruiting NCT03529396 - Safety and Efficacy of Different Regimens of Primaquine on Vivax Malaria Treatment in G6PD Deficient Patients Phase 2
Recruiting NCT05874271 - Short Course Primaquine for the Radical Cure of P. Vivax - Papua New Guinea N/A
Completed NCT05958797 - TES of Chloroquine for Pv in the Philippines in 2016
Completed NCT01716260 - Safety and Efficacy of Chloroquine and Primaquine for Vivax Malaria in Bhutan N/A
Completed NCT01288820 - Study of ACTs Plus Primaquine for Uncomplicated Plasmodium Vivax Malaria Phase 3
Completed NCT01640574 - Comparison Between 7 and 14 Day Primaquine Combined With Dihydroartemisinin-piperaquine or 3 Day Chloroquine Radical Cure of P. Vivax (BPD) Phase 3
Completed NCT01076868 - Incidence of Vivax Along the Thai Burma Border N/A
Completed NCT00158561 - Chlorproguanil/Dapsone Compared With Chloroquine and SP for Vivax Malaria Phase 3
Completed NCT01780753 - Primaquine Pharmacokinetics in Lactating Women and Their Infants Phase 1