Safety and Efficacy of Different Regimens of Primaquine on Vivax Malaria Treatment in G6PD Deficient Patients

NCT03529396 | Completed Phase 2

• 1 other identifier: CAAE: 70177317.1.0000.0005
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 2

Brief Summary

A clinical study to assess the safety and efficacy of alternative regimens of primaquine for radical cure of vivax malaria in glucose 6-phosphate dehydrogenase (G6PD) deficient. G6PD deficient patients with P. vivax monoinfection will be treated with either weekly or delayed one-week course of primaquine, and the currently recommended by national guideline, 12-week chloroquine regimen to compare treatment safety among groups. All groups will be actively monitored for hemolysis during treatment and will have six-month follow-up period to assess treatment efficacy.

Conditions

Vivax Malaria; G6PD Deficiency

Keywords

G6PD deficiency; Acute hemolytic anemia; Vivax malaria; Primaquine; Weekly primaquine; Chloroquine; Weekly chloroquine; Brazilian Amazon; Oxidative stress

Outcome Measures

Primary Outcomes (1)

• Absolute or relative change in hemoglobin < 3g/dL or 30% from baseline

  Hemoglobin reduction from baseline after exposure to primaquine for P. vivax treatment

  From date of randomization until the date of last dose, assessed up to 12 weeks.

Secondary Outcomes (3)

• Regimen efficacy

  6 months post treatment

• Adverse effects

  From date of randomization until the date of first documented event, assessed up to 12 weeks.

• Change in hemoglobin values over treatment

  through study completion: before intervention and up to 12 weeks during intervention.

Study Arms (4)

1a: Chloroquine + 5th-day Primaquine

EXPERIMENTAL

\[ARM HALTED PREMATURELY DUE TO SAFETY CONCERNS\]

Drug: Chloroquine; Drug: Primaquine

1b: Chloroquine + 8-week Primaquine

EXPERIMENTAL

26 G6PD deficient patients. Directly observed therapy.

Drug: Chloroquine; Drug: Primaquine

1c: Chloroquine + 12-week Chloroquine

ACTIVE COMPARATOR

26 G6PD deficient patients. Control group in terms of safety. Directly observed therapy.

Drug: Chloroquine

2: Standard chloroquine + primaquine

ACTIVE COMPARATOR

52 G6PD normal patients. Control group in terms of efficacy. Directly observed therapy.

Drug: Chloroquine; Drug: Primaquine

Interventions

Chloroquine DRUG

Standard chloroquine (three days)

1a: Chloroquine + 5th-day Primaquine; 1b: Chloroquine + 8-week Primaquine; 1c: Chloroquine + 12-week Chloroquine; 2: Standard chloroquine + primaquine

Primaquine DRUG

Daily Primaquine (0.5 mg of base/kg/day for seven days) starting only at the fifth day post chloroquine initiation.

1a: Chloroquine + 5th-day Primaquine

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Uncomplicated vivax malaria monoinfection
• G6PD deficiency ranging from 10%-60% of adjusted mean male activity
• Baseline hemoglobin \>9 g/dL
• Willing to comply with study requirements

You may not qualify if:

• Pregnancy or breastfeeding
• Comorbidities (hepatopathy and/or nephropathy)
• Use of antimalarials in the previous two weeks or current use of potentially hemolytic drugs
• Any condition which would place the subject at undue risk of hemolysis or interfere with the results of the study, as judged by investigator.

Sponsors & Collaborators

• Fundação de Medicina Tropical Dr. Heitor Vieira Dourado: lead
• Oswaldo Cruz Foundation: collaborator
• Conselho Nacional de Desenvolvimento Científico e Tecnológico: collaborator

Study Sites (2)

Fundação de Medicina Tropical Doutor Heitor Vieira Dourado

Manaus, Amazonas, 69040-000, Brazil

Location

Centro de Pesquisa em Medicina Tropical (Cepem)

Porto Velho, Rondônia, Brazil

Location

Related Publications (1)

• Barbosa L, Brito-Sousa J, Nascimento C, Pacheco A, Alexandre M, Alencar A, Melo M, Omena A, Souza I, Silva E, Queiroz M, Siqueira V, Rabelo C, Baia-da-Silva D, Silva D, Rocha Y, Barbosa A, Castro R, Almeida A, Brito M, Lopes A, Balieiro A, Costa M, Amaral T, Valle C, Vieira A, Gonzaga J, Pereira D, Alecrim M, Monteiro W, Lacerda M, Melo G. Safety and Efficacy of 3 Alternative Regimens Against Relapsing Plasmodium vivax Malaria in Glucose 6-Phosphate Dehydrogenase-Deficient Patients in the Brazilian Amazon (ALTPRIM). Clin Infect Dis. 2025 Dec 24;81(5):e294-e301. doi: 10.1093/cid/ciaf007.

  PMID: 39785834 DERIVED

MeSH Terms

Conditions

Malaria, Vivax; Glucosephosphate Dehydrogenase Deficiency

Interventions

Chloroquine; Primaquine

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Marcus VG Lacerda, MD, PhD

  Fiocruz/ILMD and Fundacao de Medicina Tropical Dr Heitor Vieira Dourado

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Research

Study Record Dates

• First Submitted: April 25, 2018
• First Posted: May 18, 2018
• Study Start: July 20, 2018
• Primary Completion: December 20, 2022
• Study Completion: July 6, 2023
• Last Updated: February 20, 2025

Record last verified: 2025-02

Locations

BR (2)