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

Phase 4

Recruiting

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.

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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Arm2: Primaquine low dose	Primaquine	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)
Arm2: Primaquine low dose	Artesunate	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)
Arm1: No primaquine	Artesunate	Enrolled patients will only received blood stage antimalarial (artesunate at 2 mg/kg per day every 24h for 7 days)
Arm3: Primaquine high dose	Primaquine	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)
Arm3: Primaquine high dose	Artesunate	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)

Primary Outcome Measures

Name	Time	Method
P. vivax recurrence	3 months	Proportion of patients experiencing recurrence as measured by microscopy and PCR and time to recurrence
Markers of P. vivax recurrences	3 months	Gene expression or serological markers associated with P. vivax recurrence

Secondary Outcome Measures

Name	Time	Method
Genotypes of relapsing P. vivax parasites	3 months	Genotypes of relapsing P. vivax parasites

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