- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03529396
Safety and Efficacy of Different Regimens of Primaquine on Vivax Malaria Treatment in G6PD Deficient Patients
March 28, 2023 updated by: Wuelton Marcelo Monteiro, PhD, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
Safety and Efficacy of Different Regimens of Primaquine on Vivax Malaria Treatment in Glucose 6-phosphate Dehydrogenase Deficient Patients
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.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
106
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Wuelton M Monteiro, PhD
- Phone Number: +55 (92) 2127-3498
- Email: wueltonmm@gmail.com
Study Contact Backup
- Name: Jose Diego B Sousa, BSc
- Phone Number: +55 (92) 2127-3498
- Email: sousajdb@live.com
Study Locations
-
-
Amazonas
-
Manaus, Amazonas, Brazil, 69040-000
- Fundacao De Medicina Tropical Doutor Heitor Vieira Dourado
-
-
RO
-
Porto Velho, RO, Brazil
- Centro de Pesquisa em Medicina Tropical (Cepem)
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
6 months and older (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 1a: Chloroquine + 5th-day Primaquine
[ARM HALTED PREMATURELY DUE TO SAFETY CONCERNS]
|
Standard chloroquine (three days)
Daily Primaquine (0.5 mg of base/kg/day for seven days) starting only at the fifth day post chloroquine initiation.
Weekly primaquine (0.75 mg of base/kg/week for eight weeks) starting with first dose of chloroquine.
Weekly, once a week chloroquine (5 mg of base/kg/week for twelve weeks)
Standard primaquine (0.5mg of base/kg/day for seven days) concomitant with chloroquine.
|
Experimental: 1b: Chloroquine + 8-week Primaquine
26 G6PD deficient patients.
Directly observed therapy.
|
Standard chloroquine (three days)
Daily Primaquine (0.5 mg of base/kg/day for seven days) starting only at the fifth day post chloroquine initiation.
Weekly primaquine (0.75 mg of base/kg/week for eight weeks) starting with first dose of chloroquine.
Weekly, once a week chloroquine (5 mg of base/kg/week for twelve weeks)
Standard primaquine (0.5mg of base/kg/day for seven days) concomitant with chloroquine.
|
Active Comparator: 1c: Chloroquine + 12-week Chloroquine
26 G6PD deficient patients.
Control group in terms of safety.
Directly observed therapy.
|
Standard chloroquine (three days)
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.
|
Standard chloroquine (three days)
Daily Primaquine (0.5 mg of base/kg/day for seven days) starting only at the fifth day post chloroquine initiation.
Weekly primaquine (0.75 mg of base/kg/week for eight weeks) starting with first dose of chloroquine.
Weekly, once a week chloroquine (5 mg of base/kg/week for twelve weeks)
Standard primaquine (0.5mg of base/kg/day for seven days) concomitant with chloroquine.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
From date of randomization until the date of last dose, assessed up to 12 weeks.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Regimen efficacy
Time Frame: 6 months post treatment
|
Relapse rate over follow-up period after treatment
|
6 months post treatment
|
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
|
From date of randomization until the date of first documented event, assessed up to 12 weeks.
|
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.
|
through study completion: before intervention and up to 12 weeks during intervention.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Marcus VG Lacerda, MD, PhD, Fiocruz/ILMD and Fundacao de Medicina Tropical Dr Heitor Vieira Dourado
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 20, 2018
Primary Completion (Anticipated)
July 1, 2023
Study Completion (Anticipated)
November 1, 2023
Study Registration Dates
First Submitted
April 25, 2018
First Submitted That Met QC Criteria
May 7, 2018
First Posted (Actual)
May 18, 2018
Study Record Updates
Last Update Posted (Actual)
March 29, 2023
Last Update Submitted That Met QC Criteria
March 28, 2023
Last Verified
March 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Metabolic Diseases
- Infections
- Hematologic Diseases
- Genetic Diseases, Inborn
- Vector Borne Diseases
- Anemia
- Parasitic Diseases
- Protozoan Infections
- Carbohydrate Metabolism, Inborn Errors
- Metabolism, Inborn Errors
- Anemia, Hemolytic, Congenital
- Anemia, Hemolytic
- Malaria
- Malaria, Vivax
- Glucosephosphate Dehydrogenase Deficiency
- Physiological Effects of Drugs
- Anti-Infective Agents
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Amebicides
- Filaricides
- Antinematodal Agents
- Anthelmintics
- Chloroquine
- Chloroquine diphosphate
- Primaquine
Other Study ID Numbers
- CAAE: 70177317.1.0000.0005
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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