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

University of Maryland Baltimore (UMB)

Status and phase: Completed; Phase 4

Conditions: Vivax Malaria

Treatments: Drug: Primaquine; Drug: Artesunate

Study type: Interventional

Funder types: Other

Identifiers

NCT04706130

20-0010

Details and patient eligibility

About

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.

Full 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.

Enrollment: 160 patients

Sex: All

Ages: 15+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

160 participants in 3 patient groups

Arm1: No primaquine

Other group

Description:

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

Treatment:

Drug: Artesunate

Arm2: Primaquine low dose

Other group

Description:

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)

Treatment:

Drug: Artesunate

Drug: Primaquine

Arm3: Primaquine high dose

Other group

Description:

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)

Treatment:

Drug: Artesunate

Drug: Primaquine