Clinical trial NCT03529396: Safety and Efficacy of Different Regimens of Primaquine on Vivax Malaria Treatment in G6PD Deficient Patients
Official title: Safety and Efficacy of Different Regimens of Primaquine on Vivax Malaria Treatment in Glucose 6-phosphate Dehydrogenase Deficient Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Vivax Malaria
G6PD Deficiency
Keywords: G6PD deficiency
Acute hemolytic anemia
Vivax malaria
Primaquine
Weekly primaquine
Chloroquine
Weekly chloroquine
Brazilian Amazon
Oxidative stress
Lead sponsor: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
Sponsor class: OTHER
Collaborators: name: Oswaldo Cruz Foundation
name: Conselho Nacional de Desenvolvimento Científico e Tecnológico
First posted: 2018-05-18
Enrollment: 106
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Absolute or relative change in hemoglobin < 3g/dL or 30% from baseline
timeFrame: From date of randomization until the date of last dose, assessed up to 12 weeks.
Secondary outcomes:
measure: Regimen efficacy
timeFrame: 6 months post treatment
measure: Adverse effects
timeFrame: From date of randomization until the date of first documented event, assessed up to 12 weeks.
measure: Change in hemoglobin values over treatment
timeFrame: through study completion: before intervention and up to 12 weeks during intervention.
Other outcomes:
Locations:
city: Manaus
country: Brazil
facility: Fundação de Medicina Tropical Doutor Heitor Vieira Dourado
state: Amazonas
city: Porto Velho
country: Brazil
facility: Centro de Pesquisa em Medicina Tropical (Cepem)
state: RO
Study officials:
affiliation: Fiocruz/ILMD and Fundacao de Medicina Tropical Dr Heitor Vieira Dourado
name: Marcus VG Lacerda, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: