An Ultra-short Course of Primaquine for the Radical Cure of Vivax Malaria (PRIMUS)

An Ultra-short Course of Primaquine for the Radical Cure of Vivax Malaria (PRIMUS)

Current treatment regimens to prevent relapsing malaria are too long. A shorter higher dose treatment could improve treatment outcomes, but this needs to be balanced against increased risk of side effects. Recent data from a trial in children in Papua New Guinea (PNG) suggests a shortened treatment of 3 days is safe and effective. Our multicentre trial will assess the safety and efficacy of an ultra-short primaquine course. This trial is expected to directly influence global treatment policies.

Study Overview

• Status: Not yet recruiting
• Conditions: Malaria
• Intervention / Treatment: Drug: High dose ultra short Primaquine; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 1019
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Kamala Thriemer, Professor; Phone Number: +61889468644; Email: Kamala.Ley-Thriemer@menzies.edu.au
• Study Contact Backup: Name: Hellen Mnjala, MSc; Phone Number: +61889468675; Email: hellen.mnjala@menzies.edu.au

Study Locations

• Ethiopia
  • Arba Minch
    • Arba Minch, Arba Minch, Ethiopia
      • Arba Minch University
      • Contact: Dr Tamiru Degaga; Phone Number: +252911704767; Email: drtamshib1@gmail.com
      • Principal Investigator: Dr Tamiru Degaga
  • Jimma
    • Jimma, Jimma, Ethiopia
      • Jimma University
      • Contact: Dr Daniel Yilma; Phone Number: +251471111458; Email: danielyilmab@gmail.com
      • Principal Investigator: Dr Daniel Yilma
• Indonesia
  • Lampung
    • Bandar Lampung, Lampung, Indonesia
      • Universitas Sumatera
      • Contact: Dr Ayodhia Pitaloka Pasaribu, Professor; Phone Number: +628126024392; Email: ayodhia@usu.ac.id
      • Principal Investigator: Dr Ayodhia Pitaloka Pasaribu
• Pakistan
  • Thatta
    • Karachi, Thatta, Pakistan
      • Aga Khan University, Karachi
      • Contact: Dr Asim Beg, Professor; Phone Number: +923002028490; Email: masim.beg@aku.edu
      • Principal Investigator: Dr Asim Beg
• Papua New Guinea
  • Magang
    • Port Moresby, Magang, Papua New Guinea
      • Papua New Guinea Institute of Medical Research
      • Contact: DR Moses Laman; Phone Number: +6754340208; Email: moses.laman@pngimr.org.pg
      • Principal Investigator: Dr Moses Laman

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• P. vivax peripheral parasitaemia as determined by microscopy
• G6PD normal status (G6PD activity ≥70% of the site specific adjusted male median as determined by the Standard G6PD (SD Bioline, ROK))
• Fever (temperature ≥37.5°C) or history of fever in the preceding 48 hours,
• Age ≥5 years
• Bodyweight ≥14kg
• Living in the study area and willing to be followed-up for six months

Exclusion Criteria:

• Signs or symptoms of severe malaria,
• Anaemia (defined as Hb <8g/dl) and measured by the Standard G6PD
• Pregnant or lactating
• Blood transfusion within the preceding four months
• Regular or recent use (last month) of tafenoquine, primaquine or dapsone
• Known hypersensitivity to any of the study drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: High-dose Short-course Primaquine (PQ7); Participants in this arm will receive a high-dose, short-course primaquine regimen (PQ7), consisting of a total dose of 7 mg/kg administered as 1 mg/kg once daily in the morning for 7 days (Day 0-6). A matching placebo will be given in the evening on the first three days (Day 0-2).	Drug: High dose ultra short Primaquine; High-dose, ultra-short primaquine (PQ3.5): 7mg/kg total dose given as 1mg/kg twice daily over 3.5 days (day 0, 1 and 2 morning and evening doses, and day 3 morning dose) followed by placebo as morning doses on day 4, 5 and 6.; Other: Placebo; Matching placebo administered according to the arm schedule. Morning dose on Days 4-6 for PQ3.5 arm and Evening dose on the first 3 days for PQ 7 arm).
Experimental: High dose ultra- short course Primaquine (PQ 3.5); Participants in this arm will receive a high-dose, ultra-short primaquine regimen (PQ3.5), consisting of a total dose of 7 mg/kg administered as 1 mg/kg twice daily for 3.5 days (Day 0-2 morning and evening doses, and Day 3 morning dose). A matching placebo will be given as the morning dose on Days 4-6.	Drug: High dose ultra short Primaquine; High-dose, ultra-short primaquine (PQ3.5): 7mg/kg total dose given as 1mg/kg twice daily over 3.5 days (day 0, 1 and 2 morning and evening doses, and day 3 morning dose) followed by placebo as morning doses on day 4, 5 and 6.; Other: Placebo; Matching placebo administered according to the arm schedule. Morning dose on Days 4-6 for PQ3.5 arm and Evening dose on the first 3 days for PQ 7 arm).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence risk of any recurrent vivax parasitaemia within 4 months.	The incidence risk (time to first event) of any recurrent P. vivax parasitaemia within 4 months as determined by microscopy	4 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence risk of any P. vivax parasitaemia within 6 months.	The incidence risk (time to first event) of any P. vivax parasitaemia within 6 months as determined by microscopy	6 months
Incidence of haemoglobin drop >25% to <7g/dl within 14 days of treatment.	Number of participants experiencing a haemoglobin decrease of >25% from baseline resulting in Hb<7g/dl	0-14 days
Incidence of moderate anaemia within 14 days after starting primaquine	Number of participants developing haemoglobin >=5g/dl and <7g/dl within 14 days after treatment initiation	0-14 days
Incidence of severe anaemia within 14 days after starting Primaquine	Number of participants developing haemoglobin <5g/dl within 14 days of treatment initiation.	0-14 days
• The proportion of patients requiring blood transfusion within the 6 months follow up period.	Participants requiring transfusion due to haemolysis or severe anaemia	6 months
The incidence risk of symptomatic P. vivax parasitaemia within 4 months.	The incidence risk (time to first event) of symptomatic P. vivax parasitaemia within 4 months as determined by microscopy.	4 months
Proportion of adverse events within 14 days.	The number and proportion of adverse events within 14 days after start of treatment	14 days
The number and proportion of serious adverse events.	The number and proportion of serious adverse events.	6 Months

Collaborators and Investigators

• Sponsor: Menzies School of Health Research
• Collaborators: Aga Khan University; University of Melbourne; Curtin University; Jimma University; Universitas Sumatera Utara; Papua New Guinea Institute of Medical Research; Arba Minch University; PathWest Laboratory Medicine WA
• Investigators: Principal Investigator: Kamala Thriemer, Professor, Menzies School of Health Research

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: January 13, 2026
• First Submitted That Met QC Criteria: March 9, 2026
• First Posted (Actual): March 12, 2026

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: An ultra-short course of primaquine for the radical cure of vivax malaria; PRIMUS
• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; Protozoan Infections; Parasitic Diseases; Malaria
• Other Study ID Numbers: PRIMUS; GTN2042278 (Other Grant/Funding Number: NHMRC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) underlying the results reported in this trial will be shared. This will include baseline characteristics, outcome measures, and adverse events data. Data will be available beginning [6-12 months] after publication of the primary results, and will be shared with qualified researchers upon reasonable request, following approval of a research proposal and completion of a data access agreement. Supporting documents such as the study protocol and statistical analysis plan will also be provided.
• IPD Sharing Access Criteria: All the investigators involved in the study.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No