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

Sponsor

Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (Other)

Overall Status

Recruiting

CT.gov ID

NCT03529396

Collaborator

Oswaldo Cruz Foundation (Other), Conselho Nacional de Desenvolvimento Científico e Tecnológico (Other)

104

Enrollment

Locations

Arms

55.4

Anticipated Duration (Months)

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Vivax Malaria G6PD Deficiency	Drug: Chloroquine Drug: Primaquine Drug: Primaquine 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 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 Design

Study Type:

Interventional

Anticipated 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 :

Jul 20, 2018

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

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

Regimen efficacy [6 months post treatment]
Relapse rate over follow-up period after treatment
Adverse effects [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
Change in hemoglobin values over treatment [through study completion: before intervention and up to 12 weeks during intervention.]
Absolute variation of hemoglobin levels before and during intervention.

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fundação de Medicina Tropical Doutor Heitor Vieira Dourado	Manaus	Amazonas	Brazil	69040-000
2	Centro de Pesquisa em Medicina Tropical (Cepem)	Porto Velho	RO	Brazil