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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03529396
Recruitment Status : Recruiting
First Posted : May 18, 2018
Last Update Posted : July 10, 2020
Sponsor:
Collaborators:
Oswaldo Cruz Foundation
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Information provided by (Responsible Party):
Wuelton Marcelo Monteiro, PhD, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado

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.

Condition or disease Intervention/treatment Phase
Vivax Malaria G6PD Deficiency Drug: Chloroquine Drug: Primaquine Phase 2

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, 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 104 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Different Regimens of Primaquine on Vivax Malaria Treatment in Glucose 6-phosphate Dehydrogenase Deficient Patients
Actual Study Start Date : July 20, 2018
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : July 2022


Arm Intervention/treatment
Experimental: 1a: Chloroquine + 5th-day Primaquine
[ARM HALTED PREMATURELY DUE TO SAFETY CONCERNS]
Drug: Chloroquine
Standard chloroquine (three days)

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

Experimental: 1b: Chloroquine + 8-week Primaquine
26 G6PD deficient patients. Directly observed therapy.
Drug: Chloroquine
Standard chloroquine (three days)

Drug: Primaquine
Weekly primaquine (0.75 mg of base/kg/week for eight weeks) starting with first dose of chloroquine.

Active Comparator: 1c: Chloroquine + 12-week Chloroquine
26 G6PD deficient patients. Control group in terms of safety. Directly observed therapy.
Drug: Chloroquine
Standard chloroquine (three days)

Drug: Chloroquine
Weekly, once a week chloroquine (5 mg of base/kg/week for twelve weeks)

Active Comparator: 2: Standard chloroquine + primaquine
52 G6PD normal patients. Control group in terms of efficacy. Directly observed therapy.
Drug: Chloroquine
Standard chloroquine (three days)

Drug: Primaquine
Standard primaquine (0.5mg of base/kg/day for seven days) concomitant with chloroquine.




Primary Outcome Measures :
  1. Absolute or relative change in hemoglobin < 3g/dL or 30% from baseline [ Time Frame: From date of randomization until the date of last dose, assessed up to 12 weeks. ]
    Hemoglobin reduction from baseline after exposure to primaquine for P. vivax treatment


Secondary Outcome Measures :
  1. Regimen efficacy [ Time Frame: 6 months post treatment ]
    Relapse rate over follow-up period after treatment

  2. Adverse effects [ Time Frame: From date of randomization until the date of first documented event, assessed up to 12 weeks. ]
    Presence of adverse reactions as a result of intervention, measured by clinical and laboratory tests

  3. Change in hemoglobin values over treatment [ Time Frame: through study completion: before intervention and up to 12 weeks during intervention. ]
    Absolute variation of hemoglobin levels before and during intervention.



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Ages Eligible for Study:   6 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03529396


Contacts
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Contact: Wuelton M Monteiro, PhD +55 (92) 99165 2486 wueltonmm@gmail.com
Contact: Jose Diego B Sousa, BSc +55 (92) 99166-9617 sousajdb@live.com

Locations
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Brazil
Fundação de Medicina Tropical Doutor Heitor Vieira Dourado Recruiting
Manaus, Amazonas, Brazil, 69040-000
Contact: Wuelton M Monteiro, PhD    +55 (92) 2127 3498    wueltonmm@gmail.com   
Sponsors and Collaborators
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
Oswaldo Cruz Foundation
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Investigators
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Principal Investigator: Marcus VG Lacerda, MD, PhD Fiocruz/ILMD and Fundacao de Medicina Tropical Dr Heitor Vieira Dourado
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Responsible Party: Wuelton Marcelo Monteiro, PhD, Director of Research, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
ClinicalTrials.gov Identifier: NCT03529396    
Other Study ID Numbers: CAAE: 70177317.1.0000.0005
First Posted: May 18, 2018    Key Record Dates
Last Update Posted: July 10, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Wuelton Marcelo Monteiro, PhD, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado:
G6PD deficiency
Acute hemolytic anemia
Vivax malaria
Primaquine
Weekly primaquine
Chloroquine
Weekly chloroquine
Brazilian Amazon
Oxidative stress
Additional relevant MeSH terms:
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Malaria
Malaria, Vivax
Glucosephosphate Dehydrogenase Deficiency
Protozoan Infections
Parasitic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Genetic Diseases, Inborn
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Metabolic Diseases
Chloroquine
Chloroquine diphosphate
Primaquine
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Antimalarials
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Filaricides