Operational Feasibility of Appropriate Radical Cure of Plasmodium Vivax With Tafenoquine or Primaquine After Quantitative G6PD Testing in Brazil

NCT ID: NCT05096702

Last Updated: 2023-06-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

16000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-09-09

Study Completion Date

2023-09-09

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Malaria, Vivax G6PD Deficiency

Study Design

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Observational Model Type

ECOLOGIC_OR_COMMUNITY

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Tafenoquine

Intervention Type DRUG

Tafenoquine 300 mg (2x150mg tablets)

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.

Primaquine

Intervention Type DRUG

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

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.

Primaquine

Intervention Type DRUG

Weekly primaquine adjusted by weight (0.75mg/kg/week for 8 weeks)

Interventions

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Tafenoquine

Tafenoquine 300 mg (2x150mg tablets)

Intervention Type DRUG

Primaquine

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

Intervention Type DRUG

Primaquine

Weekly primaquine adjusted by weight (0.75mg/kg/week for 8 weeks)

Intervention Type DRUG

Other Intervention Names

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Kozenis

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

None
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Centro de Pesquisa em Medicina Tropical

UNKNOWN

Sponsor Role collaborator

Medicines for Malaria Venture

OTHER

Sponsor Role collaborator

Ministry of Health, Brazil

OTHER_GOV

Sponsor Role collaborator

Secretária Municipal de Saúde de Manaus

UNKNOWN

Sponsor Role collaborator

Secretária Estadual de Saúde do Amazonas

UNKNOWN

Sponsor Role collaborator

Fundação de Medicina Tropical Dr. Heitor Vieira Dourado

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Marcus Lacerda, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Fundação de Medicina Tropical Dr. Heitor Vieira Dourado

Dhelio Batista, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Centro de Pesquisa em Medicina Tropical (CEPEM)

Locations

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Fundação de Medicina Tropical Dr Heitor Vieira Dourado

Manaus, Amazonas, Brazil

Site Status

Bela Vista

Manaus, Amazonas, Brazil

Site Status

Campos Salles (Base)

Manaus, Amazonas, Brazil

Site Status

Colônia Antônio Aleixo

Manaus, Amazonas, Brazil

Site Status

Cooperativa I

Manaus, Amazonas, Brazil

Site Status

Cueiras (UBSR)

Manaus, Amazonas, Brazil

Site Status

Efigênio Salles (UBSR)

Manaus, Amazonas, Brazil

Site Status

Grande Vitória

Manaus, Amazonas, Brazil

Site Status

João Paulo II

Manaus, Amazonas, Brazil

Site Status

Pau Rosa (UBSR)

Manaus, Amazonas, Brazil

Site Status

Platão Araújo (Base)

Manaus, Amazonas, Brazil

Site Status

Santa Inês

Manaus, Amazonas, Brazil

Site Status

São Pedro (UBSR)

Manaus, Amazonas, Brazil

Site Status

União da Vitória

Manaus, Amazonas, Brazil

Site Status

Centro de Pesquisa em Medicina Tropical (Cepem)

Porto Velho, Rondônia, Brazil

Site Status

UBS Abunã

Porto Velho, Rondônia, Brazil

Site Status

UBS Agrovila

Porto Velho, Rondônia, Brazil

Site Status

UBS Calama

Porto Velho, Rondônia, Brazil

Site Status

UBS Calderita

Porto Velho, Rondônia, Brazil

Site Status

UBS Cujubim

Porto Velho, Rondônia, Brazil

Site Status

UBS Extrema

Porto Velho, Rondônia, Brazil

Site Status

UBS Fortaleza do Abunã

Porto Velho, Rondônia, Brazil

Site Status

UBS Jacy-Paraná

Porto Velho, Rondônia, Brazil

Site Status

UBS José Adelino

Porto Velho, Rondônia, Brazil

Site Status

UBS Nazaré

Porto Velho, Rondônia, Brazil

Site Status

UBS Nova Califórnia

Porto Velho, Rondônia, Brazil

Site Status

UBS Nova Mutum

Porto Velho, Rondônia, Brazil

Site Status

UBS Palmares

Porto Velho, Rondônia, Brazil

Site Status

UBS Rio das Garças

Porto Velho, Rondônia, Brazil

Site Status

UBS Rio Pardo

Porto Velho, Rondônia, Brazil

Site Status

UBS Ronaldo Aragão

Porto Velho, Rondônia, Brazil

Site Status

UBS São Carlos

Porto Velho, Rondônia, Brazil

Site Status

UBS União Bandeirantes

Porto Velho, Rondônia, Brazil

Site Status

UBS Vila DNIT

Porto Velho, Rondônia, Brazil

Site Status

UBS Vista Alegre

Porto Velho, Rondônia, Brazil

Site Status

Upa Zona Leste

Porto Velho, Rondônia, Brazil

Site Status

SPA Hospital Chapot Prevost

Manaus, , Brazil

Site Status

Upa Campos Sales

Manaus, , Brazil

Site Status

UPA Danilo Corrêa

Manaus, , Brazil

Site Status

UPA José Rodrigues

Manaus, , Brazil

Site Status

Policlínica Ana Adelaide

Rondônia, , Brazil

Site Status

Countries

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Brazil

References

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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.

Reference Type DERIVED
PMID: 38452779 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38365417 (View on PubMed)

Other Identifiers

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CAAE: 16867319.6.0000.0008

Identifier Type: -

Identifier Source: org_study_id

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