Clinical trial NCT06306300: Safety and Efficacy of Decentralized HCV Treatment vs Standard-of-Care in Rio de Janeiro (Brazil)
Official title: Randomized Open-label and Non-inferiority Clinical Trial to Evaluate the Safety, Adherence, and Cost-effectiveness of Simplified and Decentralized Hepatitis C Treatment in Primary Health Care Compared to Standard-of-care in the Brazilian Public Health System
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Hepatitis C
Keywords: Hepatitis C virus
Primary health care
Hepatitis C virus self-test
Lead sponsor: Oswaldo Cruz Foundation
Sponsor class: OTHER
Collaborators: name: Conselho Nacional de Desenvolvimento Científico e Tecnológico
First posted: 2024-03-12
Enrollment: 30000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Study I is a population-based cross-sectional screening study (n=30,000 individuals) to determine the prevalence of HCV infection in people attending a Basic Health Care Unit. The sub-study associated with Study I is a cross-sectional study to assess the usability of a self-test for the detection of HCV antibodies in oral fluid (n=1,500 participants included in Study I). Study II is a phase IV open-label randomized clinical trial (1:1) to evaluate the non-inferiority of simplified and decentralized hepatitis C treatment ("Simplified-and-Decentralized (SD) HCV treatment"; experimental arm) compared to specialist reference treatment ("Standard-of-Care (SC) HCV treatment"; control arm) within the SUS.
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: Up to 650,000 people in Brazil are living with chronic hepatitis c virus (HCV) infection. Hepatitis C is a silent disease, and up to 20% of cases can progress to liver cirrhosis and its complications. Rapid tests for diagnosis of HCV infection and non-invasive methods for detecting liver cirrhosis are available in the Brazilian Public Health System. Additionally, safe and highly effective drugs (direct-acting antivirals, DAAs) have been delivered for free for hepatitis C treatment by the Brazilian Unified Health System (Sistema Único de Saúde, SUS) since 2015. Sustained virological response (SVR) rates with DAAs in studies conducted in Brazil and Latin America were higher than 90%. Despite the availability of rapid tests for early diagnosis and effective drugs, the HCV continuum of care remains deficient in Brazil. It is estimated that only 10% of individuals known to have hepatitis C achieve HCV cure (SVR). This is explained by multiple barriers from diagnosis to treatment access, such as low rates of population screening (HCVST are not available in Brazil) and few available slots in tertiary centers for hepatitis C treatment by specialists. International studies have described that SVR rates by simplified hepatitis C treatment performed by non-specialists in the Primary Care System were similar to those treated in tertiary centers by specialists (standard-of-care). However, the optimal strategy for managing hepatitis C within the Brazilian-SUS remains unclear.This project aims to evaluate the improve of the HCV continuum of care by a implementation of a test-and-treat strategy in the Primary Care System in Brazil. The project consists of two parallel studies (and a sub-study).

The project consists of two parallel studies (and a sub-study). Study I is a population-based cross-sectional screening study using rapid tests to determine the prevalence of HCV infection in people attending a Basic Health Care Unit. The sub-study associated with Study I is a cross-sectional study to assess the usability of a self-test for the detection of HCV antibodies in oral fluid (participants included in Study I). Study II is a phase IV open-label randomized clinical trial to evaluate the non-inferiority of simplified and decentralized hepatitis C treatment ("Simplified-and-Decentralized (SD) HCV treatment"; experimental arm) compared to specialist reference treatment ("Standard-of-Care (SC) HCV treatment"; control arm) within the SUS.

Detailed description: In Brazil, liver cirrhosis was the cause of death for over 265,000 people between 2000 and 2012. The mortality rate from cirrhosis in 2012 was 12 deaths per 100,000 inhabitants, and the number of deaths from liver cirrhosis increased by about 22% in the last decade.

Recently, hepatitis C treatment has been revolutionized by the use of direct-acting antivirals (DAAs), which are safe and highly effective oral medications. Cure rates for hepatitis C, known as sustained virological response (SVR), in studies conducted in Brazil and Latin America were higher than 90%. Hepatitis C cure (SVR) is associated with a reduction in the incidence of HCC, the need for liver transplantation, improvement in quality of life, and a decrease in HCV transmission. These new medications have been available for hepatitis C treatment through the Brazilian Public Health System, known as Sistema Único de Saúde (SUS) since 2015.

The Ministry of Health of Brazil signed an agreement with the WHO in 2016 and with the goal of defining public health strategies to eliminate viral hepatitis by 2030, reducing new infections by 90% and global hepatitis-related mortality by 65%.

Identifying individuals with HCV infection is crucial for the (micro) elimination of hepatitis C. The majority of chronically infected HCV patients are asymptomatic until the development of liver cirrhosis and/or its complications. Therefore, screening for HCV infection should be performed in individuals, even when asymptomatic, through HCV antibody (HCVab) test. Currently, HCV rapid tests (HCVRT) in fingerstick blood with results in 15-20 minutes are available in Brazil.

Historically, HCV screening was recommended for individuals over 40 years of age and high-risk populations for HCV infection, such as people who inject drugs (PWID), prisoners, and men who have sex with men (MSM). However, recent international guidelines recommend screening for all individuals aged 18-79. Active HCV infection should be confirmed by detecting HCV viral load using molecular tests by polymerase chain reaction (PCR). Currently, the identification of HCV-RNA by PCR as a point-of-care tests (PoCT), GeneXpert® System, is also possible. The Xpert HCV VL Fingerstick test has excellent accuracy for detecting HCV-RNA in fingerstick blood, providing results in up to 105 minutes.. Liver elastography is a rapid imaging method (\< 5 minutes), similar to abdominal ultrasound, painless, and free of complications, that can be performed at the bedside and provides real-time results for fibrosis stage/liver cirrhosis diagnosis. The technical principle of this method is based on measuring the propagation of ultrasound waves, called shear waves, through the liver parenchyma, estimating the organ's fibrosis degree through liver stiffness measurement (LSM). Currently, portable/semi-portable hepatic elastography devices are available, allowing for the staging of liver fibrosis in regions with difficult access to healthcare.

Globally, the HCV continuum of care is still deficient, as only about 10% of identified hepatitis C patients achieve SVR. Brazil also observes a similar scenario of deficiencies in the HCV cascade of care. People living with HCV are typically treated in tertiary centers by specialists (infectious disease specialists, hepatologists, gastroenterologists). Multiple pre-treatment visits (diagnostic confirmation, biological analyses, and staging of liver fibrosis) are required, along with visits during treatment (clinical visits and biological analyses) and after medication use (evaluation of hepatitis C cure). This process can be even more complicated in certain stigmatized, highly vulnerable populations, and/or those with difficult access to healthcare. The hepatitis C treatment cascade can be improved, especially with recent advances in techniques for diagnosing/confirming HCV infection and the availability of pan-genotypic and simple therapeutic regimens (one tablet orally per day for 12 weeks, "one-size-fits-all"), extremely safe and highly effective (even in patients with advanced fibrosis/liver cirrhosis). The simplification of hepatitis C treatment leads to higher detection and treatment rates (increased access to treatment), rapid initiation of treatment post-diagnosis (rapid linkage-to-care), reduced HCV transmission (treatment as a prevention tool), and cost reduction associated with cirrhosis complications/liver transplantation. Additionally, international studies have described that the response rates to hepatitis C treatment by non-specialists in the Primary Health Care System with DAAs seems to be similar to those treated by specialists. However, the best strategy for managing hepatitis C within the Brazilian-SUS is not yet widely defined.

Eligibility criteria: Study I and Sub-Study

Inclusion Criteria:

- Age between 18-79 years-old

Exclusion Criteria:

* Presence of a disease that need urgent/emergency treatment and/or acute febrile illness, such as COVID-19, Dengue, Zyca virus infection or Chikungunya
* Lack of capacity to sign the informed consent or refuse to participate

Study II

Inclusion Criteria:

* Age between 18 and 79 years old.
* Presence of active/chronic hepatitis C, defined by a positive HCVab test and detectable HCV-RNA

Exclusion Criteria:

* Children and adolescents (\< 18 years old)
* Pregnancy, defined by a positive β-HCG urinary test
* Lactating individuals
* Co-infection with HBV or HIV
* Regular use of medications with potential drug interactions or contraindication for co-administration with SOF/VEL
* Presence of severe acute illness, active neoplasia, solid organ transplant, or use of immunosuppressive medications
* Presence of clinical signs of decompensated liver cirrhosis (ascites, hepatic encephalopathy, report of a recent episode of gastrointestinal bleeding within the last 12 weeks)

Primary outcomes:
measure: Prevalence of HCV infection
timeFrame: 1 month
measure: The effectiveness of the HCV treatment with test results.
timeFrame: 1 month
measure: Usability of the result of a self-test HCV
timeFrame: 1 month
Secondary outcomes:
measure: Proportion between positive and negative
timeFrame: 1 month
measure: Participants with fibrosis/cirrhosis
timeFrame: 1 month
measure: Participants who denied the treatment
timeFrame: 1 month
measure: cost per detected participant
timeFrame: 1 month
measure: Unscheduled visits during treatment
timeFrame: 3 months
measure: Improvement of liver fibrosis stage
timeFrame: 1 year
measure: Quality of life data
timeFrame: 1 month
measure: Cost of treatment for participant
timeFrame: 1 month
measure: Adherence to treatment
timeFrame: 1 month
Other outcomes:
measure: Participant´s Ability to use the test
timeFrame: 1 month
measure: Participant preference for types of tests
timeFrame: 1 month
measure: Participant understanding to interpret his result
timeFrame: 1 month
measure: Test Performance
timeFrame: 1 month
measure: Test Accuracy
timeFrame: 1 month
Locations:
city: Rio de Janeiro
country: Brazil
facility: Evandro Chagas National Institute of Infectious Diseases
state: Rio De Janeiro/RJ
city: Rio De Janeiro
country: Brazil
facility: Hugo Perazzo
Study officials:
References: