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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Vivax Malaria

Intervention / Treatment
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* Drug: Primaquine
* Drug: Artesunate


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study will be an open-labelled randomized clinical trial to determine therapeutic efficacy.
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |