Clinical trial NCT05096702: Operational Feasibility of Appropriate Radical Cure of Plasmodium Vivax With Tafenoquine or Primaquine After Quantitative G6PD Testing in Brazil
Official title: Operational Feasibility of Appropriate Radical Cure of Plasmodium Vivax With Tafenoquine or Primaquine After Quantitative G6PD Testing in Brazil
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Malaria, Vivax
G6PD Deficiency
Keywords: G6PD deficiency
tafenoquine
primaquine
G6PD screening
Operational study
Brazil
Lead sponsor: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
Sponsor class: OTHER
Collaborators: name: Centro de Pesquisa em Medicina Tropical
name: Medicines for Malaria Venture
name: Ministry of Health, Brazil
name: Secretária Municipal de Saúde de Manaus
name: Secretária Estadual de Saúde do Amazonas
First posted: 2021-10-27
Enrollment: 16000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: ECOLOGIC_OR_COMMUNITY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_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).

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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

None

Primary outcomes:
measure: Percentage of P. vivax patients ≥16 years of age treated or not with TQ according to the appropriate level of G6PD enzyme activity.
timeFrame: After the inclusion of 600 patients, approximately 15 months after study start.
Secondary outcomes:
measure: Percentage of patients with P. vivax ≥6 months treated or not with PQ according to the appropriate level of G6PD enzyme activity
timeFrame: 15 months after study start
measure: Description of the characteristics of patients treated with TQ or PQ
timeFrame: 15 months after study start
measure: Frequency of drug-induced acute hemolytic anemia (AHA)
timeFrame: 15 months after study start
measure: Hospitalization due to confirmed drug-induced AHA
timeFrame: 15 months after study start
Other outcomes:
Locations:
city: Manaus
country: Brazil
facility: Fundação de Medicina Tropical Dr Heitor Vieira Dourado
state: Amazonas
city: Manaus
country: Brazil
facility: Bela Vista
state: AM
city: Manaus
country: Brazil
facility: Campos Salles (Base)
state: AM
city: Manaus
country: Brazil
facility: Colônia Antônio Aleixo
state: AM
city: Manaus
country: Brazil
facility: Cooperativa I
state: AM
city: Manaus
country: Brazil
facility: Cueiras (UBSR)
state: AM
city: Manaus
country: Brazil
facility: Efigênio Salles (UBSR)
state: AM
city: Manaus
country: Brazil
facility: Grande Vitória
state: AM
city: Manaus
country: Brazil
facility: João Paulo II
state: AM
city: Manaus
country: Brazil
facility: Pau Rosa (UBSR)
state: AM
city: Manaus
country: Brazil
facility: Platão Araújo (Base)
state: AM
city: Manaus
country: Brazil
facility: Santa Inês
state: AM
city: Manaus
country: Brazil
facility: São Pedro (UBSR)
state: AM
city: Manaus
country: Brazil
facility: União da Vitória
state: AM
city: Porto Velho
country: Brazil
facility: Upa Zona Leste
state: Rondonia
city: Porto Velho
country: Brazil
facility: Centro de Pesquisa em Medicina Tropical (Cepem)
state: RO
city: Porto Velho
country: Brazil
facility: UBS Abunã
state: RO
city: Porto Velho
country: Brazil
facility: UBS Agrovila
state: RO
city: Porto Velho
country: Brazil
facility: UBS Calama
state: RO
city: Porto Velho
country: Brazil
facility: UBS Calderita
state: RO
city: Porto Velho
country: Brazil
facility: UBS Cujubim
state: RO
city: Porto Velho
country: Brazil
facility: UBS Extrema
state: RO
city: Porto Velho
country: Brazil
facility: UBS Fortaleza do Abunã
state: RO
city: Porto Velho
country: Brazil
facility: UBS Jacy-Paraná
state: RO
city: Porto Velho
country: Brazil
facility: UBS José Adelino
state: RO
city: Porto Velho
country: Brazil
facility: UBS Nazaré
state: RO
city: Porto Velho
country: Brazil
facility: UBS Nova Califórnia
state: RO
city: Porto Velho
country: Brazil
facility: UBS Nova Mutum
state: RO
city: Porto Velho
country: Brazil
facility: UBS Palmares
state: RO
city: Porto Velho
country: Brazil
facility: UBS Rio das Garças
state: RO
city: Porto Velho
country: Brazil
facility: UBS Rio Pardo
state: RO
city: Porto Velho
country: Brazil
facility: UBS Ronaldo Aragão
state: RO
city: Porto Velho
country: Brazil
facility: UBS São Carlos
state: RO
city: Porto Velho
country: Brazil
facility: UBS União Bandeirantes
state: RO
city: Porto Velho
country: Brazil
facility: UBS Vila DNIT
state: RO
city: Porto Velho
country: Brazil
facility: UBS Vista Alegre
state: RO
city: Manaus
country: Brazil
facility: SPA Hospital Chapot Prevost
city: Manaus
country: Brazil
facility: Upa Campos Sales
city: Manaus
country: Brazil
facility: UPA Danilo Corrêa
city: Manaus
country: Brazil
facility: UPA José Rodrigues
city: Rondônia
country: Brazil
facility: Policlínica Ana Adelaide
Study officials:
affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
name: Marcus Lacerda, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro de Pesquisa em Medicina Tropical (CEPEM)
name: Dhelio Batista, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: