NCT05096702

Brief Summary

This is an observational study carried out in Brazil in patients with P. vivax malaria. The study will be carried out in the municipalities of Manaus (state of Amazonas) and Porto Velho (state of Rondônia). G6PD and TQ tests will be provided to health facilities by municipal health authorities using the common route for the provision of drugs and diagnostics. PQ and other antimalarial drugs are already available in Brazil. Designated personnel at the health facilities will be trained to perform the G6PD quantitative test procedure and the radical healing treatment algorithm by the Lead Researcher (RP) team and municipal authorities using teaching materials developed by the sponsors. The study design is based on the secondary use of data routinely collected from all malaria patients in the Epidemiological Surveillance Information System for Malaria (SIVEP-Malaria) by the Ministry of Health (MS). Data from all malaria patients are routinely collected through SIVEP forms by health professionals (HP) and entered into the SIVEP database by the municipality staff. The SIVEP form will be adapted by the MS to collect information about the G6PD test, TQ treatment and signs of hemolysis. The retrospective data from all patients will be entered into a new database by the municipality staff during the study period and the relevant data will be automatically exported weekly to the SIVEP database. The study team will only have access to unidentified data, according to the access levels that will be assigned to each member in the system. Only the municipality's team will have access to the identified patient data. In addition to the data collected on the SIVEP forms, the PR team will ask the two referral hospitals that routinely receive all admissions due to AHA to perform a regular screening of electronic hospital admission records for patients with signs of AHA (renal failure, jaundice, blood transfusion, malaria). All identified cases will be investigated using hospital records and SIVEP forms. Confirmed information about drug-induced AHA will be linked to the patient record recorded in the database. The PR team will also contribute to pharmacovigilance training. Physicians at tertiary-level health units will report side effects through the VigiMed system, from the National Health Surveillance Agency (ANVISA).Finally, the additional costs of implementing the G6PD and TQ tests will be collected along with the study at the health facilities. Since the study is based on retrospective data collection, and the adoption of TQ and G6PD testing will be done by the municipality, the G6PD testing and the treatment of patients with TQ or PQ will be carried out in accordance with the treatment policy , that is, regardless of the study. The study will be carried out in phases: \- 1st phase (approximately 3 months): Training and provision of G6PD and TQ tests will initially be limited to 10 high-complexity and intermediate-complexity units (referral hospitals, hospitals, emergency care units, polyclinics). Data will be collected from patients with P. vivax treated at these health facilities. An interim analysis will be performed after collecting data from 600 patients with P. vivax ≥ 16 years, who have not been treated for vivax malaria in the past 60 days, in the study database in order to decide whether the study can be extended to less complex health units. The decision will be made by an Independent Study Oversight Committee (ISOC). If the interim results of Phase 1 are found to be unsatisfactory, ISOC may decide not to extend the study to primary care units until improvements in the educational program are implemented and/or additional support is provided to health professionals. Additional interim analyzes will be performed as appropriate. \- 2nd phase (approximately 9 months) \[CURRENT PHASE\]: if approved by ISOC, the study will be extended to less complex health units (basic health units, family health units and other primary care services) and other high and medium complexity of health in the selected municipalities. After staff training, G6PD and TQ testing will be provided to these health facilities by municipal health authorities. During this 2nd phase, data will continue to be collected from patients with P. vivax treated by the 1st phase tertiary care units. \- An additional interim analysis will be performed after data from 600 patients with P. vivax ≥16 years old, who have not been treated for P. vivax malaria in the past 60 days, from primary care units are collected in the study database ( approximately 3 months after the start of the 2nd phase). The study will continue while the interim analyzes are being carried out. Final results will be analyzed and validated by ISOC. The study is expected to take approximately 15 months.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
16,000

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Sep 2021

Geographic Reach
1 country

41 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 9, 2021

Completed
18 days until next milestone

First Submitted

Initial submission to the registry

September 27, 2021

Completed
1 month until next milestone

First Posted

Study publicly available on registry

October 27, 2021

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 30, 2022

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

September 9, 2023

Completed
Last Updated

June 13, 2023

Status Verified

June 1, 2023

Enrollment Period

12 months

First QC Date

September 27, 2021

Last Update Submit

June 9, 2023

Conditions

Keywords

G6PD deficiencytafenoquineprimaquineG6PD screeningOperational studyBrazil

Outcome Measures

Primary Outcomes (1)

  • Percentage of P. vivax patients ≥16 years of age treated or not with TQ according to the appropriate level of G6PD enzyme activity.

    After the inclusion of 600 patients, approximately 15 months after study start.

Secondary Outcomes (4)

  • Percentage of patients with P. vivax ≥6 months treated or not with PQ according to the appropriate level of G6PD enzyme activity

    15 months after study start

  • Description of the characteristics of patients treated with TQ or PQ

    15 months after study start

  • Frequency of drug-induced acute hemolytic anemia (AHA)

    15 months after study start

  • Hospitalization due to confirmed drug-induced AHA

    15 months after study start

Study Arms (3)

Tafenoquine (TQ)

Patients aged ≥16 years, G6PD activity ≥ 6.1 IU/gHb, not pregnant or breastfeeding, will receive single-dose TQ in addition to standard blood schizonticidal drug.

Drug: Tafenoquine

Daily primaquine (PQ) for 7 days

Patients aged ≥ 6 months, with G6PD activity between 4.1 and 6.0 IU/gHb, not pregnant or breastfeeding for \< 1 month, will receive daily PQ in addition to standard blood schizonticidal drug.

Drug: Primaquine

Weekly primaquine for 8 weeks

Patients aged ≥ 6 months, with G6PD activity ≤ 4.0 IU/gHb, not pregnant or breastfeeding for \< 1 month, will receive weekly once-a-week PQ for eight weeks in addition to standard blood schizonticidal drug.

Drug: Primaquine

Interventions

Tafenoquine 300 mg (2x150mg tablets)

Also known as: Kozenis
Tafenoquine (TQ)

Daily primaquine adjusted by weight (0.5 mg/kg/day for 7 days)

Daily primaquine (PQ) for 7 days

Eligibility Criteria

Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

The study will be carried out in Brazil, in the municipalities of Manaus (state of Amazonas) and Porto Velho (state of Rondônia).Relevant staff members at health facilities will be trained by RP staff and municipal authorities using educational material on the need and use of G6PD testing, treatment algorithm based on G6PD activity levels, TQ adverse events and PQ, identifying, reporting and managing adverse events to ANVISA and MS (completion of the SIVEP DEMO form).

You may qualify if:

  • Diagnosis of P. vivax malaria (parasitologically confirmed by microscopy or rapid diagnostic test) over six months of age.

You may not qualify if:

  • None

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (41)

Fundação de Medicina Tropical Dr Heitor Vieira Dourado

Manaus, Amazonas, 69040000, Brazil

Location

Bela Vista

Manaus, Amazonas, Brazil

Location

Campos Salles (Base)

Manaus, Amazonas, Brazil

Location

Colônia Antônio Aleixo

Manaus, Amazonas, Brazil

Location

Cooperativa I

Manaus, Amazonas, Brazil

Location

Cueiras (UBSR)

Manaus, Amazonas, Brazil

Location

Efigênio Salles (UBSR)

Manaus, Amazonas, Brazil

Location

Grande Vitória

Manaus, Amazonas, Brazil

Location

João Paulo II

Manaus, Amazonas, Brazil

Location

Pau Rosa (UBSR)

Manaus, Amazonas, Brazil

Location

Platão Araújo (Base)

Manaus, Amazonas, Brazil

Location

Santa Inês

Manaus, Amazonas, Brazil

Location

São Pedro (UBSR)

Manaus, Amazonas, Brazil

Location

União da Vitória

Manaus, Amazonas, Brazil

Location

Centro de Pesquisa em Medicina Tropical (Cepem)

Porto Velho, Rondônia, Brazil

Location

UBS Abunã

Porto Velho, Rondônia, Brazil

Location

UBS Agrovila

Porto Velho, Rondônia, Brazil

Location

UBS Calama

Porto Velho, Rondônia, Brazil

Location

UBS Calderita

Porto Velho, Rondônia, Brazil

Location

UBS Cujubim

Porto Velho, Rondônia, Brazil

Location

UBS Extrema

Porto Velho, Rondônia, Brazil

Location

UBS Fortaleza do Abunã

Porto Velho, Rondônia, Brazil

Location

UBS Jacy-Paraná

Porto Velho, Rondônia, Brazil

Location

UBS José Adelino

Porto Velho, Rondônia, Brazil

Location

UBS Nazaré

Porto Velho, Rondônia, Brazil

Location

UBS Nova Califórnia

Porto Velho, Rondônia, Brazil

Location

UBS Nova Mutum

Porto Velho, Rondônia, Brazil

Location

UBS Palmares

Porto Velho, Rondônia, Brazil

Location

UBS Rio das Garças

Porto Velho, Rondônia, Brazil

Location

UBS Rio Pardo

Porto Velho, Rondônia, Brazil

Location

UBS Ronaldo Aragão

Porto Velho, Rondônia, Brazil

Location

UBS São Carlos

Porto Velho, Rondônia, Brazil

Location

UBS União Bandeirantes

Porto Velho, Rondônia, Brazil

Location

UBS Vila DNIT

Porto Velho, Rondônia, Brazil

Location

UBS Vista Alegre

Porto Velho, Rondônia, Brazil

Location

Upa Zona Leste

Porto Velho, Rondônia, Brazil

Location

SPA Hospital Chapot Prevost

Manaus, 69055010, Brazil

Location

Upa Campos Sales

Manaus, Brazil

Location

UPA Danilo Corrêa

Manaus, Brazil

Location

UPA José Rodrigues

Manaus, Brazil

Location

Policlínica Ana Adelaide

Rondônia, Brazil

Location

Related Publications (2)

  • Brito M, Rufatto R, Brito-Sousa JD, Murta F, Sampaio V, Balieiro P, Baia-Silva D, Castro V, Alves B, Alencar A, Duparc S, Grewal Daumerie P, Borghini-Fuhrer I, Jambert E, Peterka C, Edilson Lima F Jr, Carvalho Maia L, Lucena Cruz C, Maciele B, Vasconcelos M, Machado M, Augusto Figueira E, Alcirley Balieiro A, Batista Pereira D, Lacerda M. Operational effectiveness of tafenoquine and primaquine for the prevention of Plasmodium vivax recurrence in Brazil: a retrospective observational study. Lancet Infect Dis. 2024 Jun;24(6):629-638. doi: 10.1016/S1473-3099(24)00074-4. Epub 2024 Mar 4.

  • Brito M, Rufatto R, Murta F, Sampaio V, Balieiro P, Baia-Silva D, Castro V, Alves B, Alencar A, Duparc S, Grewal Daumerie P, Borghini-Fuhrer I, Jambert E, Peterka C, Edilson Lima F Jr, Carvalho Maia L, Lucena Cruz C, Maciele B, Vasconcelos M, Machado M, Augusto Figueira E, Alcirley Balieiro A, Menezes A, Ataides R, Batista Pereira D, Lacerda M. Operational feasibility of Plasmodium vivax radical cure with tafenoquine or primaquine following point-of-care, quantitative glucose-6-phosphate dehydrogenase testing in the Brazilian Amazon: a real-life retrospective analysis. Lancet Glob Health. 2024 Mar;12(3):e467-e477. doi: 10.1016/S2214-109X(23)00542-9.

MeSH Terms

Conditions

Malaria, VivaxGlucosephosphate Dehydrogenase Deficiency

Interventions

tafenoquinePrimaquine

Condition Hierarchy (Ancestors)

MalariaProtozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne DiseasesAnemia, Hemolytic, CongenitalAnemia, HemolyticAnemiaHematologic DiseasesHemic and Lymphatic DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesCarbohydrate Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

AminoquinolinesQuinolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Marcus Lacerda, MD, PhD

    Fundação de Medicina Tropical Dr. Heitor Vieira Dourado

    PRINCIPAL INVESTIGATOR
  • Dhelio Batista, MD, PhD

    Centro de Pesquisa em Medicina Tropical (CEPEM)

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
ECOLOGIC OR COMMUNITY
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 27, 2021

First Posted

October 27, 2021

Study Start

September 9, 2021

Primary Completion

August 30, 2022

Study Completion

September 9, 2023

Last Updated

June 13, 2023

Record last verified: 2023-06

Data Sharing

IPD Sharing
Will not share

Locations