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

Fundação de Medicina Tropical Dr. Heitor Vieira Dourado

Status and phase: Active, not recruiting; Phase 2

Conditions: Vivax Malaria; G6PD Deficiency

Treatments: Drug: Primaquine; Drug: Chloroquine

Study type: Interventional

Funder types: Other

Identifiers

NCT03529396

CAAE: 70177317.1.0000.0005

Details and patient eligibility

About

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.

Full 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.

Enrollment: 106 patients

Sex: All

Ages: 6+ months old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

106 participants in 4 patient groups

1a: Chloroquine + 5th-day Primaquine

Experimental group

Description:

\[ARM HALTED PREMATURELY DUE TO SAFETY CONCERNS\]

Treatment:

Drug: Primaquine

Drug: Primaquine

Drug: Chloroquine

Drug: Primaquine

Drug: Chloroquine

1b: Chloroquine + 8-week Primaquine

Experimental group

Description:

26 G6PD deficient patients. Directly observed therapy.

Treatment:

Drug: Primaquine

Drug: Primaquine

Drug: Chloroquine

Drug: Primaquine

Drug: Chloroquine

1c: Chloroquine + 12-week Chloroquine

Active Comparator group

Description:

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

Treatment:

Drug: Chloroquine

Drug: Chloroquine

2: Standard chloroquine + primaquine

Active Comparator group

Description:

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

Treatment:

Drug: Primaquine

Drug: Primaquine

Drug: Chloroquine

Drug: Primaquine

Drug: Chloroquine