Rigorous Assessment of P. Vivax Relapses and Primaquine Efficacy for Radical Cure

NCT04706130 | Completed Phase 4 DMC

• 1 other identifier: 20-0010
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

The study will be an open-labelled randomized clinical trial to determine therapeutic efficacy. Note that this will not be an Investigational New Drug application, as only World Health Organization (WHO)-approved drugs will be used at dosage and for conditions approved.

Conditions

Vivax Malaria

Outcome Measures

Primary Outcomes (2)

• P. vivax recurrence

  Proportion of patients experiencing recurrence as measured by microscopy and PCR and time to recurrence

  3 months

• Markers of P. vivax recurrences

  Gene expression or serological markers associated with P. vivax recurrence

  3 months

Secondary Outcomes (1)

• Genotypes of relapsing P. vivax parasites

  3 months

Study Arms (3)

Arm1: No primaquine

OTHER

Enrolled patients will only received blood stage antimalarial (artesunate at 2 mg/kg per day every 24h for 7 days)

Drug: Artesunate

Arm2: Primaquine low dose

OTHER

Enrolled patients will received blood stage antimalarial (artesunate at 2 mg/kg per day every 24h for 7 days) and primaquine at 0.25 mg/kg/day for 14 days (starting at day 7)

Drug: Primaquine; Drug: Artesunate

Arm3: Primaquine high dose

OTHER

Enrolled patients will received blood stage antimalarial (artesunate at 2 mg/kg per day every 24h for 7 days) and primaquine at 0.50 mg/kg/day for 14 days (starting at day 7)

Drug: Primaquine; Drug: Artesunate

Interventions

Primaquine DRUG

After treatment of the blood stage infection, enrolled participants will receive either no primaquine, a low dose of primaquine or a high dose of primaquine against liver parasites

Arm2: Primaquine low dose; Arm3: Primaquine high dose

Artesunate DRUG

All enrolled participants will receive a 7-day treatment of artesunate ((2 mg/kg/day) to clear blood-stage parasites

Arm1: No primaquine; Arm2: Primaquine low dose; Arm3: Primaquine high dose

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 15 and older
• Acute (within 10 days), symptomatic (i.e., history of fever), uncomplicated malaria caused solely by Plasmodium vivax (verified by PCR)
• G6PD normal (as determined by quantitative spectrophotometric assay)

You may not qualify if:

• Pregnant, planning to become pregnant or lactating women,
• Received antimalarial drugs in the past month,
• Hb \< 8g/dL, \< 1,500 neutrophils/μl, or signs of complicated malaria (e.g., vomiting, convulsions,…),
• History of primaquine, artesunate or artesunate-mefloquine allergy or intolerance,
• PCR-positivity for severe acute respiratory syndrome coronavirus 2.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• National Centre for Parasitology, Entomology and Malaria Control, Cambodia: collaborator
• Institut Pasteur du Cambodge: collaborator

Study Sites (1)

Institut Pasteur du Cambodge

Phnom Penh, Cambodia

Location

Related Publications (2)

• Eng V, Lek D, Sin S, Feufack-Donfack LB, Orban A, Salvador J, Seng D, Heng S, Khim N, Tebben K, Flamand C, Sommen C, van der Pluijm RW, White M, Witkowski B, Serre D, Popovici J. 14 days of high-dose versus low-dose primaquine treatment in patients with Plasmodium vivax infection in Cambodia: a randomised, single-centre, open-label efficacy study. Lancet Infect Dis. 2025 Aug;25(8):884-895. doi: 10.1016/S1473-3099(25)00033-7. Epub 2025 Mar 17.

  PMID: 40112852 DERIVED

• Eng V, Lek D, Sin S, Feufack-Donfack LB, Orban A, Salvador J, Seng D, Heng S, Khim N, Tebben K, Flamand C, Sommen C, van der Pluijm RW, White M, Witkowski B, Serre D, Popovici J. High versus low dose of 14 days treatment of primaquine in Plasmodium vivax infected patients in Cambodia: a randomised open-label efficacy study. medRxiv [Preprint]. 2025 Jan 2:2025.01.01.25319862. doi: 10.1101/2025.01.01.25319862.

  PMID: 39802788 DERIVED

MeSH Terms

Conditions

Malaria, Vivax

Interventions

Primaquine; Artesunate

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: The study will be an open-labelled randomized clinical trial to determine therapeutic efficacy.

Study Record Dates

• First Submitted: January 8, 2021
• First Posted: January 12, 2021
• Study Start: April 15, 2021
• Primary Completion: October 1, 2024
• Study Completion: October 1, 2024
• Last Updated: March 28, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)