Effectiveness of Novel Approaches to Radical Cure With Tafenoquine and Primaquine (EFFORT)

Effectiveness of Novel Approaches to Radical Cure With Tafenoquine and Primaquine - a Randomized Controlled Trial in P. Vivax Patients

Health care facility based, randomized, controlled, open label, superiority trial with 3 arms

Study Overview

• Status: Recruiting
• Conditions: Vivax Malaria; Malaria, Vivax; Plasmodium Vivax; Malaria Relapse
• Intervention / Treatment: Drug: Primaquine; Drug: Tafenoquine

Detailed Description

• To assess the effectiveness of a short-course of high dose primaquine (total dose 7mg/kg given unsupervised over 7 days) compared to the current standard low dose primaquine regimen (total dose 3.5mg/kg given unsupervised over 14 days).
• To assess the effectiveness of tafenoquine (single dose of 300mg) compared to the short-course high dose primaquine regimen.
• To assess the safety of tafenoquine compared to the high and low dose primaquine regimens.
• To assess the cost-effectiveness and feasibility of high dose primaquine and tafenoquine compared to the current low dose primaquine regimen

• Study Type: Interventional
• Enrollment (Estimated): 960
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Kamala Thriemer, MD, MPH, PhD; Phone Number: 0889468644; Email: kamala.ley-thriemer@menzies.edu.au

Study Locations

• Cambodia
  • Kampong Speu, Cambodia
    • Not yet recruiting
    • Chambak Health Center
    • Contact: Rupam Tripura, MD
    • Principal Investigator: Lek Dysoley, MD
    • Sub-Investigator: Rupam Tripura, MD
    • Sub-Investigator: James Callery, MD
    • Principal Investigator: Lorenz Seidlein, MD
    • Sub-Investigator: Thomas Peto, MD
  • Stung Treng, Cambodia
    • Recruiting
    • Siem Pang Health Centre
    • Contact: Rupam Tripura, MD
    • Principal Investigator: Lorenz von Seidlein, MD
    • Principal Investigator: Lek Dysoley, MD
    • Sub-Investigator: Rupam Tripura, MD
    • Sub-Investigator: Tom Peto, PhD
    • Sub-Investigator: James Callery, MD
  • Pursat Province
    • Pursat, Pursat Province, Cambodia
      • Recruiting
      • Kravanh District Hospital
      • Contact: Rupam Tripura, MD
      • Principal Investigator: Lorenz von Seidlein, MD
      • Principal Investigator: Lek Dysoley, MD
      • Sub-Investigator: Rupam Tripura, MD
      • Sub-Investigator: Tom Peto, PhD
      • Sub-Investigator: James Callery, MD
• Ethiopia
  • Arba Minch, Ethiopia
    • Recruiting
    • Arba Minch General Hospital
    • Contact: Tamiru Shibiru Degaga, MD
• Indonesia
  • Sumatera
    • Labuhanbatu, Sumatera, Indonesia
      • Recruiting
      • Tanjung Leidong Health Center
      • Contact: Ayodhia Pasaribu Pitaloka, MD
• Pakistan
  • Karachi, Pakistan
    • Not yet recruiting
    • Aga Khan Hospital Karachi
    • Contact: Asim Beg, MD
    • Principal Investigator: Asim Beg, MD
    • Sub-Investigator: Najia Ghanchi, MD
    • Sub-Investigator: Momin Kazi, MD
    • Sub-Investigator: Farah Qamar, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 98 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• P. vivax peripheral parasitaemia (mono-infection) as determined by microscopy
• G6PD normal status (G6PD activity ≥ 70% of the adjusted male median as determined by the Biosensor™ (SD Biosensor, ROK))
• Fever (temperature ≥37.5⁰C) or history of fever in the preceding 48 hours
• Age ≥18 years
• Written informed consent
• Living in the study area and willing to be followed for six months

Exclusion Criteria:

• Danger signs or symptoms of severe malaria
• Anaemia (defined as Hb <8g/dl)
• Pregnant or lactating females
• Known hypersensitivity to any of the study drugs
• Regular use of drugs with haemolytic potential

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Patients are treated with schizontocidal treatment plus low dose PQ (total dose 3.5mg/kg) unsupervised over 14 days (PQ14)
Experimental: PQ Intervention; Patients are treated with schizontocidal treatment plus high dose PQ (total dose 7 mg/kg) unsupervised over 7 days (PQ7)	Drug: Primaquine; patients are treated with schizontocidal treatment plus high dose PQ (total dose 7 mg/kg) unsupervised over 7 days (PQ7); Other Names: Primaquine 7 days
Experimental: TQ Intervention; Patients are treated with schizontocidal treatment plus a single dose of Tafenoquine (TQ)	Drug: Tafenoquine; patients are treated with schizontocidal treatment plus a single dose of Tafenoquine (TQ).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence risk any P vivax PQ7 / PQ14	The incidence risk (time to first event) of any P. vivax parasitaemia during the 6-month follow up period as determined by microscopy compared between the PQ7 arm and the control arm (PQ14).	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence risk symptomatic P vivax TQ / PQ14	The incidence risk (time to first event) of symptomatic P. vivax parasitaemia during the 6 months follow up period as determined by microscopy compared between TQ and the control arm (PQ14).	6 months
Incidence risk any P vivax PQ7 / TQ	• The incidence risk (time to first event) of any P. vivax parasitaemia during the 6 months follow up period as determined by microscopy compared between PQ7 and TQ arms	6 months
Incidence risk any P vivax PQ14 / TQ	The incidence risk (time to first event) of any P. vivax parasitaemia during the 6 months follow up period as determined by microscopy compared between PQ14 and TQ arms	6 months
Incidence risk any P vivax PQ7 / TQ	The incidence risk (time to first event) of any P. vivax parasitaemia during the 6 months follow up period as determined by microscopy compared between PQ7 and TQ arms	6 months
Incidence risk any P vivax PQ7 / PQ14	The incidence risk (time to first event) of symptomatic P. vivax parasitaemia during the 6-month follow up period as determined by microscopy compared between the PQ7 arm and the control arm (PQ14).	6 months

Collaborators and Investigators

• Sponsor: Menzies School of Health Research
• Collaborators: Aga Khan University; University of Melbourne; Universitas Sumatera Utara; Ethiopian Public Health Institute; Mahidol Oxford Tropical Medicine Research Unit; Arba Minch University; National Centre for Parasitology, Entomology and Malaria Control, Cambodia
• Investigators: Principal Investigator: Kamala Thriemer, MD, MPH, PhD, Menzies School of Health Research

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2021
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): September 30, 2024

Study Registration Dates

• First Submitted: May 28, 2020
• First Submitted That Met QC Criteria: May 28, 2020
• First Posted (Actual): June 2, 2020

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: primaquine; tafenoquine
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Mosquito-Borne Diseases; Malaria; Malaria, Vivax; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Primaquine; Tafenoquine
• Other Study ID Numbers: EFFORT

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. Data collected for the study, including individual patient data and the final trial dataset are reserved for the chief investigator and co-investigators of the trial. The trial will be reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines. Trial results will be published in peer-reviewed open access journals and disseminated to trial stakeholders, including participants, as per ethical guidelines.
• IPD Sharing Access Criteria: The data are available for access via the WorldWide Antimalarial Resistance Network (WWARN.org). Requests for access will be reviewed by a Data Access Committee to ensure that 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 by email to malariaDAC@iddo.org via the Data Access Form available at WWARN.org/accessing-data. The WWARN is registered with the Registry of Research Data Repositories (re3data.org).
• 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
• product manufactured in and exported from the U.S.: No