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

Vivax Malaria Clinical Trial

Official title:

Safety and Efficacy of Different Regimens of Primaquine on Vivax Malaria Treatment in Glucose 6-phosphate Dehydrogenase Deficient Patients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03529396
• Other study ID #: CAAE: 70177317.1.0000.0005
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 20, 2018
• Est. completion date: November 2023

Study information

• Verified date: March 2023
• Source: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 106
• Est. completion date: November 2023
• Est. primary completion date: July 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months and older

Eligibility

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.

Related Conditions & MeSH terms

• G6PD Deficiency
• Glucosephosphate Dehydrogenase Deficiency
• Malaria
• Malaria, Vivax
• Vivax Malaria

Intervention

Drug:
• Chloroquine
Standard chloroquine (three days)
• Primaquine
Daily Primaquine (0.5 mg of base/kg/day for seven days) starting only at the fifth day post chloroquine initiation.
• Primaquine
Weekly primaquine (0.75 mg of base/kg/week for eight weeks) starting with first dose of chloroquine.
• Chloroquine
Weekly, once a week chloroquine (5 mg of base/kg/week for twelve weeks)
• Primaquine
Standard primaquine (0.5mg of base/kg/day for seven days) concomitant with chloroquine.

Locations

Country	Name	City	State
Brazil	Fundação de Medicina Tropical Doutor Heitor Vieira Dourado	Manaus	Amazonas
Brazil	Centro de Pesquisa em Medicina Tropical (Cepem)	Porto Velho	RO

Sponsors (3)

Lead Sponsor	Collaborator
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado	Conselho Nacional de Desenvolvimento Científico e Tecnológico, Oswaldo Cruz Foundation

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Regimen efficacy	Relapse rate over follow-up period after treatment	6 months post treatment
Secondary	Adverse effects	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.
Secondary	Change in hemoglobin values over treatment	Absolute variation of hemoglobin levels before and during intervention.	through study completion: before intervention and up to 12 weeks during intervention.