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

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.

Study Overview

• Status: Recruiting
• Conditions: Vivax Malaria
• Intervention / Treatment: Drug: Artesunate; Drug: Primaquine

Detailed Description

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-approved drugs will be used at dosage and for conditions approved.

Eligible patients willing to participate will first be tested prior to enrolment for their glucose-6-phosphate dehydrogenase (G6PD) status by the gold standard spectrophotometric analysis. The investigators will exclude from the study any G6PD deficient (or intermediate females) patient. Treatment allocation will be randomized between i) 7 days of artesunate (2 mg/kg/day for 7 days) alone (Arm1), ii) same artesunate regimen + 0.25 mg/kg/day 14 days of primaquine (Arm2) and iii) same artesunate regimen + 0.5 mg/kg/day 14 days of primaquine (Arm3). All patients will be relocated to a no-transmission city to make sure they are not reinfected during the follow-up. Follow-up will be performed every 24-48h for 90 days. At the end of the follow-up period, all patients that did not receive primaquine (arm1) will be treated according to national guidelines (14 days at 0.25mg/kg/day). Patients will additionally be followed monthly for three months after the end of the relocation.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 4

Contacts and Locations

Study Locations

• Cambodia
  • Phnom Penh, Cambodia
    • Recruiting
    • Institut Pasteur du Cambodge
    • Contact: Jean Popovici, Ph.D.; Phone Number: 089 851 806; Email: jpopovici@pasteur-kh.org
    • Principal Investigator: Jean Popovici, PhD
    • Principal Investigator: Benoit Witkowski, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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.

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
Other: Arm1: No primaquine; Enrolled patients will only received blood stage antimalarial (artesunate at 2 mg/kg per day every 24h for 7 days)	Drug: Artesunate; All enrolled participants will receive a 7-day treatment of artesunate ((2 mg/kg/day) to clear blood-stage parasites
Other: Arm2: Primaquine low dose; 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: Artesunate; All enrolled participants will receive a 7-day treatment of artesunate ((2 mg/kg/day) to clear blood-stage parasites; Drug: Primaquine; 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
Other: Arm3: Primaquine high dose; 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: Artesunate; All enrolled participants will receive a 7-day treatment of artesunate ((2 mg/kg/day) to clear blood-stage parasites; Drug: Primaquine; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genotypes of relapsing P. vivax parasites	Genotypes of relapsing P. vivax parasites	3 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: January 8, 2021
• First Submitted That Met QC Criteria: January 11, 2021
• First Posted (Actual): January 12, 2021

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Mosquito-Borne Diseases; Malaria, Vivax; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Anthelmintics; Schistosomicides; Antiplatyhelmintic Agents; Primaquine; Artesunate
• Other Study ID Numbers: 20-0010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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