Primaquine Double Dose for Radical Cure of Plasmodium Vivax in Colombia

NCT05232227 | Withdrawn Phase 2 DMC

• 1 other identifier: 21-34422
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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).

Conditions

Malaria, Vivax; Relapse

Keywords

Plasmodium vivax; Radical cure regimen; Primaquine double dose (PQdd); Colombia

Outcome Measures

Primary Outcomes (1)

• Incidence risk of microscopy-detectable P. vivax infections

  The incidence risk (time to first event) of microscopy-detectable P. vivax infection (sexual and asexual parasitemias), comparing PQdd14 to PQsd14.

  6-month follow-up

Secondary Outcomes (1)

• relapse efficacy

  6-month follow-up

Study Arms (2)

Standard regimen Primaquine single dose over 14 days

ACTIVE COMPARATOR

The standard regimen consists of administering Chloquine Phosphate 10 mg/kg on days 1 and 2, and 5 mg/kg on day 3 plus Primaquine Phosphate 3.5 mg/kg divided over 14 days (0.25mg/kg/day)

Drug: Primaquine single dose over 14 days

Treatment regimen Primaquine double dose over 14 days

EXPERIMENTAL

The treatment regimen consists of administering Chloquine Phosphate 10 mg/kg on days 1 and 2, and 5 mg/kg on day 3 plus Primaquine Phosphate 7 mg/kg divided over 14 days

Drug: Primaquine double dose over 14 days

Interventions

Primaquine double dose over 14 days DRUG

Primaquine Phosphate tablets New Drug Application (NDA): 008316 Company: SANOFI AVENTIS US Chloroquine Phosphate tablets

Also known as: Primaquine Phosphate tablets

Treatment regimen Primaquine double dose over 14 days

Primaquine single dose over 14 days DRUG

Primaquine Phosphate tablets New Drug Application (NDA): 008316 Company: SANOFI AVENTIS US

Also known as: Primaquine Phosphate tablets

Standard regimen Primaquine single dose over 14 days

Eligibility Criteria

• Age: 5 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• Pan American Health Organization: collaborator

MeSH Terms

Conditions

Malaria, Vivax; Recurrence

Interventions

Primaquine

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: A randomized open-label superiority trial
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2021
• First Posted: February 9, 2022
• Study Start: January 20, 2023
• Primary Completion: June 5, 2023
• Study Completion: October 30, 2023
• Last Updated: May 11, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share