Rigorous Assessment of P. Vivax Relapses and Primaquine Efficacy for Radical Cure
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
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 Design
Arms and Interventions
| 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: 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
Drug: Artesunate
All enrolled participants will receive a 7-day treatment of artesunate ((2 mg/kg/day) to clear blood-stage 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: 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
Drug: Artesunate
All enrolled participants will receive a 7-day treatment of artesunate ((2 mg/kg/day) to clear blood-stage parasites
|
Outcome Measures
Primary Outcome Measures
- 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
- Genotypes of relapsing P. vivax parasites [3 months]
Genotypes of relapsing P. vivax parasites
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Institut Pasteur du Cambodge | Phnom Penh | Cambodia |
Sponsors and Collaborators
- University of Maryland, Baltimore
- National Centre for Parasitology, Entomology and Malaria Control, Cambodia
- Institut Pasteur du Cambodge
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 20-0010