Primaquine Double Dose for Radical Cure of Plasmodium Vivax in Colombia

• Status: Not yet recruiting
• Trial end date: 2023-04-30
• Target enrollment: 0
• Participant gender: All

Summary

Primaquine (PQ) is the only widely available treatment to prevent P. vivax relapses. World Health Organization recommends increased PQ doses in East Asia and Oceania, frequently relapsing strains. In 2005, the Centers for Diseases Control and Prevention began also recommending higher dose PQ to treat infections from all parts of the world.

In Latin America, PQ for a radical cure has been largely implemented as 3.5 mg/kg over 14 days (standard dose, long-course, PQsd14) or 3.5 mg/kg over 7 days (short-course, or PQsd7) in combination with chloroquine (CQ). A recent randomized controlled trial in Brazil showed that a 7 mg/kg double dose regimen over 14 days (PQdd14) was superior in preventing relapses compared to the standard of care regimen in Brazil of 3.5 mg/kg over 7 PQsd7 Direct Observed Therapy (DOT) and PQsd7 without DOT and with or 14 days PQsd14 with DOT (92% versus 66% were relapse-free in the 6-month follow-up in adjusted analyses). These data were presented at the 2019 PAHO Malaria Technical Advisory Group (TAG) meeting. To inform whether there should be a policy change by Panamerican Health Organization, the Malaria TAG recommended more evidence from the results of another trial to confirm the efficacy of high versus low-dose PQ. This project aims to generate the necessary evidence to inform a policy decision regarding high-dose PQ.

Impact Malaria (IM) proposes to conduct another trial, per the PAHO Malaria TAG's recommendation, assessing the efficacy of high-dose PQ compared to low-dose PQ. The objective is to compare a standard regimen, which in Colombia is PQsd14 (3,5mg/kg divided in 14 days), to a double dose alternative PQ 7 mg/kg double dose regimen over 14 days (PQdd14).

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, San Francisco
• Collaborator: Pan American Health Organization
• Treatments: Primaquine

Criteria

Inclusion Criteria:

• Age ≥5 years

• Fever (T≥37.5 ⁰C, oral) and/or history of fever in the previous 48 hours

• P. vivax mono-infection

• Normal G6PD status using Biosensor™ (SD Bioline, ROK) (G6PD activity ≥ 70% of the adjusted male median (AMM))

• Written informed consent

• Living in the study area and willing to be followed for six months

Exclusion Criteria:

• Malaria treatment in the previous 30 days,

• Self-reported chronic disease (including severe cardiac, hepatic, or renal disorders, malnutrition, or HIV),

• Clinically significant concurrent illness,

• Use of medications known to interfere with the pharmacokinetics of PQ or CQ,

• Known hypersensitivity to any of the study drugs,

• Use of an investigational drug within the previous 30 days or five half-lives (whichever was longer),

• History of moderate or severe adverse reaction to any of the study drugs,

• Hemoglobin < 7 g/dL,

• Pregnancy (by urine pregnancy test) or breastfeeding,

• Not able to take oral treatment,

• Signs of severe malaria:

• Unable to drink

• Vomiting (more than twice in the previous 24 hours)

• Recent history of convulsions (one or more in the previous 24 hours)

• Impaired consciousness

• Unable to sit or stand

• Cerebral malaria (unarousable coma)

• Severe anemia (hematocrit <15% or clinical signs) hemoglobin <5 mg/ml) (Note: we will use hemoglobin less than 7 mg/ml as exclusion criteria)

• Renal failure (serum creatinine >3 mg/dL or clinical signs)

• Pulmonary edema

• Hypoglycemia (blood glucose <40mg/dL or clinical signs)

• Shock (systolic blood pressure <70 mm Hg in adults; 50 mm Hg in children)

• Spontaneous bleeding/disseminated intravascular coagulation.

• Repeated generalized convulsions

• Acidemia/acidosis (clinical signs)

• Macroscopic hemoglobinuria

• Jaundice●