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

Primary Purpose

Vivax Malaria, G6PD Deficiency

Status
Active
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Chloroquine
Primaquine
Primaquine
Chloroquine
Primaquine
Sponsored by
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Vivax Malaria focused on measuring G6PD deficiency, Acute hemolytic anemia, Vivax malaria, Primaquine, Weekly primaquine, Chloroquine, Weekly chloroquine, Brazilian Amazon, Oxidative stress

Eligibility Criteria

6 Months - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.

Sites / Locations

  • Fundação de Medicina Tropical Doutor Heitor Vieira Dourado
  • Centro de Pesquisa em Medicina Tropical (Cepem)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Active Comparator

Active Comparator

Arm Label

1a: Chloroquine + 5th-day Primaquine

1b: Chloroquine + 8-week Primaquine

1c: Chloroquine + 12-week Chloroquine

2: Standard chloroquine + primaquine

Arm Description

[ARM HALTED PREMATURELY DUE TO SAFETY CONCERNS]

26 G6PD deficient patients. Directly observed therapy.

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

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

Outcomes

Primary Outcome Measures

Absolute or relative change in hemoglobin < 3g/dL or 30% from baseline
Hemoglobin reduction from baseline after exposure to primaquine for P. vivax treatment

Secondary Outcome Measures

Regimen efficacy
Relapse rate over follow-up period after treatment
Adverse effects
Presence of adverse reactions as a result of intervention, measured by clinical and laboratory tests
Change in hemoglobin values over treatment
Absolute variation of hemoglobin levels before and during intervention.

Full Information

First Posted
April 25, 2018
Last Updated
March 28, 2023
Sponsor
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
Collaborators
Oswaldo Cruz Foundation, Conselho Nacional de Desenvolvimento Científico e Tecnológico
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1. Study Identification

Unique Protocol Identification Number
NCT03529396
Brief Title
Safety and Efficacy of Different Regimens of Primaquine on Vivax Malaria Treatment in G6PD Deficient Patients
Official Title
Safety and Efficacy of Different Regimens of Primaquine on Vivax Malaria Treatment in Glucose 6-phosphate Dehydrogenase Deficient Patients
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 20, 2018 (Actual)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
November 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
Collaborators
Oswaldo Cruz Foundation, Conselho Nacional de Desenvolvimento Científico e Tecnológico

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.
Detailed Description
This is an open-label, randomized, phase II, clinical trial of safety and efficacy. Patients will be screened for eligibility and treated at the Fundação de Medicina Tropical Dr Heitor Vieira Dourado in Manaus and the Centro de Pesquisa em Medicina Tropical (Cepem) in Porto Velho, Brazil. A total of 104 vivax malaria patients will be recruited into the study, 52 G6PD deficient (Arm 1) and 52 G6PD normal (Arm 2). Patients with spectrophotometrically-confirmed G6PD deficiency (10-60% of adjusted mean male activity) will be divided into three subgroups of 10 patient each. All arms will receive standard 3-day chloroquine course. Additionally, Arm 1a will receive a delayed course of primaquine for 7 days, starting only at the fifth-day post-chloroquine initiation [ARM HALTED DUE TO SAFETY CONCERNS]. Arm 1b will receive weekly primaquine, once a week, for 8 weeks. Arm 1c will receive prophylactic 12-week course of chloroquine, as recommended by national guidelines for such patients (control group in terms of safety). Arm 2, the control group of efficacy, will receive standard regimen, comprised of 3-day chloroquine plus concomitant 7-day primaquine. All patients will receive directly observed therapy (DOT) and will be closely monitored for clinical parameters and laboratory markers of hemolysis including hemoglobin, methemoglobin, lactate dehydrogenase, haptoglobin, reticulocytes, indirect bilirubin, aspartate aminotransferase, and urinalysis. All groups will be followed for 6 months after treatment to assess relapse rate. Primary endpoint is the tolerability of the regimens defined by hemoglobin fall. Secondary endpoints include treatment failure (relapse during follow-up), frequency of adverse effects, and rate of hemoglobin fall during treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vivax Malaria, G6PD Deficiency
Keywords
G6PD deficiency, Acute hemolytic anemia, Vivax malaria, Primaquine, Weekly primaquine, Chloroquine, Weekly chloroquine, Brazilian Amazon, Oxidative stress

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
106 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1a: Chloroquine + 5th-day Primaquine
Arm Type
Experimental
Arm Description
[ARM HALTED PREMATURELY DUE TO SAFETY CONCERNS]
Arm Title
1b: Chloroquine + 8-week Primaquine
Arm Type
Experimental
Arm Description
26 G6PD deficient patients. Directly observed therapy.
Arm Title
1c: Chloroquine + 12-week Chloroquine
Arm Type
Active Comparator
Arm Description
26 G6PD deficient patients. Control group in terms of safety. Directly observed therapy.
Arm Title
2: Standard chloroquine + primaquine
Arm Type
Active Comparator
Arm Description
52 G6PD normal patients. Control group in terms of efficacy. Directly observed therapy.
Intervention Type
Drug
Intervention Name(s)
Chloroquine
Intervention Description
Standard chloroquine (three days)
Intervention Type
Drug
Intervention Name(s)
Primaquine
Intervention Description
Daily Primaquine (0.5 mg of base/kg/day for seven days) starting only at the fifth day post chloroquine initiation.
Intervention Type
Drug
Intervention Name(s)
Primaquine
Intervention Description
Weekly primaquine (0.75 mg of base/kg/week for eight weeks) starting with first dose of chloroquine.
Intervention Type
Drug
Intervention Name(s)
Chloroquine
Intervention Description
Weekly, once a week chloroquine (5 mg of base/kg/week for twelve weeks)
Intervention Type
Drug
Intervention Name(s)
Primaquine
Intervention Description
Standard primaquine (0.5mg of base/kg/day for seven days) concomitant with chloroquine.
Primary Outcome Measure Information:
Title
Absolute or relative change in hemoglobin < 3g/dL or 30% from baseline
Description
Hemoglobin reduction from baseline after exposure to primaquine for P. vivax treatment
Time Frame
From date of randomization until the date of last dose, assessed up to 12 weeks.
Secondary Outcome Measure Information:
Title
Regimen efficacy
Description
Relapse rate over follow-up period after treatment
Time Frame
6 months post treatment
Title
Adverse effects
Description
Presence of adverse reactions as a result of intervention, measured by clinical and laboratory tests
Time Frame
From date of randomization until the date of first documented event, assessed up to 12 weeks.
Title
Change in hemoglobin values over treatment
Description
Absolute variation of hemoglobin levels before and during intervention.
Time Frame
through study completion: before intervention and up to 12 weeks during intervention.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marcus VG Lacerda, MD, PhD
Organizational Affiliation
Fiocruz/ILMD and Fundacao de Medicina Tropical Dr Heitor Vieira Dourado
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fundação de Medicina Tropical Doutor Heitor Vieira Dourado
City
Manaus
State/Province
Amazonas
ZIP/Postal Code
69040-000
Country
Brazil
Facility Name
Centro de Pesquisa em Medicina Tropical (Cepem)
City
Porto Velho
State/Province
RO
Country
Brazil

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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