Monitoring of Hepatitis C Treatment Using Telemedicine - a Clinical Trial in Public Health System in Brazil

Monitoring of Hepatitis C Therapy Using Telemedicine in a Simplified Protocol With Pangenotypic Regimen in Non-cirrhotic Patients - a Single Group Clinical Trial in the National Public Health System in Brazil

The study is a non-randomized, single group clinical trial on monitoring hepatitis C therapy using telemedicine. Patients with chronic hepatitis C without cirrhosis will be treated with the pangenotypic regimen of direct acting antivirals sofosbuvir and velpatasvir for 12 weeks after a single visit to the clinic, in which treatment will be prescribed. Patients will be then monitored by telemedicine tools, like instant message application, telephone and video calls and by his or her primary physician when needed. Twelve weeks after treatment conclusion, hepatitis C virus RNA levels will be measured on a blood sample, indicating the cure rate and efficacy of this protocol on HCV treatment.

The primary objective of the study is to address the feasibility and applicability of the usage of telemedicine tools to increase access and monitor HCV treatment with direct-acting antivirals in public health in Brazil.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Hepatitis C
• Intervention / Treatment: Other: Telemedicine; Drug: Velpatasvir/Sofosbuvir

Detailed Description

Scientific rationale

It's estimated that 0.7% of the Brazilian population is infected with hepatitis C virus (HCV). In March 2018, the Ministry of Health defined all patients with HCV to be able to receive direct-acting antivirals (DAAs) from the public health system without any charges. Though this "universal-access policy", frequently there are still many obstacles for patients to actually get at the treatment: patients living in cities distant from big centres and underserved by specialized physicians in the country, lack of medical doctors experienced in HCV treatment in the public system, delay between prescription and starting of medications because of administrative issues, and socioeconomic vulnerability among people.

Telemedicine tools are powerful ways of reaching people living distant from big centres, and there are some successful international experiences with hepatitis C treatment in this field, like Project ECHO® (Extension for Community Healthcare Outcomes). In Brazil, there is a national program, geographically located in Porto Alegre, that uses telemedicine to improve healthcare quality in primary care by offering continuous education and teleconsultations (by text or toll-free hotline) to community physicians and other healthcare professionals working in public primary care institutions all over the country.

Primary objective

To address the applicability of telemedicine tools to increase access and monitor HCV treatment with direct-acting antivirals in public health in Brazil.

Research methods

HCV-infected patients in the waiting list for specialized consultation with gastroenterologist or infectious disease physician will be recruited to a meeting that will consist of a HCV lecture followed by individual, focused consultation with medical history, analysis of previous lab results (including fibrosis evaluation by the AST-to-platelets ratio index - APRI) and collection of blood samples. All patients will receive a prescription of pan-genotypic DAA sofosbuvir and velpatasvir regimen for 12 weeks according to the Brazilian Ministry of Health's Treatment Protocol, along with orientations about use and potential side effects and ways to contact the telemedicine centre - mobile phone instant messages and WhatsApp® messages, phone calls and video calls. Issues regarding the administrative process will be held by the study team and medications will be delivered to each patient's city or region at the time they're available.

Before starting treatment, patients will be oriented about treatment administration, its potential side effects and ways of contacting the research team by text messages, phone calls and, when appropriate, teleconsultation by video teleconference with the patient and one of the healthcare professionals of the study. During the treatment course, adverse effects will be monitored and, when present, graded by the Division of AIDS (DAIDS) Table from the National Institutes of Health.

The family physicians working in each patient area will be oriented about this study and HCV treatment. Moreover, they will be invited to join the regular Project ECHO® meetings held by the Brazilian centre located at Porto Alegre. Healthcare professionals also have the toll-free hotline to get in touch with the telemedicine program and investigators. HCV-RNA will be collected 12 weeks after the end of therapy at a local institution next to patient home or city.

• Study Type: Interventional
• Enrollment (Actual): 144
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-007
      • Hospital de Clínicas de Porto Alegre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have voluntarily signed the informed consent form;
• Chronic hepatitis C confirmed by positive HCV-RNA;
• Have been referred to specialized consultation in gastroenterology or infectious disease in the Brazilian Public Health System in Porto Alegre;
• Have previous fibrosis staging (eg. liver biopsy, Fibroscan®) or laboratory tests for APRI score calculation.

Exclusion Criteria:

• Suspicion or diagnosis of cirrhosis based on:
• Hepatic elastography ≥12.5 kPa on Fibroscan®;
• APRI score ≥2.0;
• Clinical, ultrasound or endoscopic evidence of cirrhosis or portal hypertension;
• Previous HCV treatment with direct acting antivirals;
• HIV coinfection with antiretroviral treatment incompatible with HCV antivirals;
• Previous solid organ transplant;
• Significant comorbidity that may interfere with the HCV treatment
• Creatinine clearance < 30 mL/min;
• Platelets < 150.000/mL;
• Pregnant or breastfeeding female;
• Woman of childbearing age without use or that does not accept to use effective contraception during treatment and during the 30 days after treatment end;
• Inability or unwillingness to provide informed consent or abide by the requirements of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Telemedicine; Sofosbuvir 400mg and velpatasvir 100mg qd for 12 weeks Telemedicine support	Other: Telemedicine; Telemedicine monitoring and teleconsultation by video calls; Drug: Velpatasvir/Sofosbuvir; Velpatasvir 100mg / Sofosbuvir 400mg once a day for twelve weeks; Other Names: Epclusa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained virologic response	Proportion of treated patients with undetectable hepatitis C virus RNA levels measured by a real time polymerase chain reaction (PCR) with a lower limit of detection ≤ 12 IU/mL	12 weeks post end of antiviral therapy (SVR12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence to antiviral treatment	Proportion of patients with treatment completion	12 weeks after antiviral treatment initiation
Patient satisfaction with the treatment	Patient satisfaction with the telemedicine support measured by a a questionnaire applied to all participants	12 weeks post end of antiviral therapy (SVR12)
Adverse effects	Incidence of adverse effects related to treatment reported by patients	12 weeks post end of antiviral therapy (SVR12)
Severe adverse effects	Incidence of severe or life threatening (grade 3 or 4) adverse effects related to treatment reported by patients	12 weeks post end of antiviral therapy (SVR12)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of primary physicians participation after invitation to project ECHO®	To address the participation rate on Project ECHO® meetings of primary care physicians who referred patients enrolled in the study	12 weeks post end of antiviral therapy (SVR12)

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Collaborators: Ministry of Health, Brazil; TelessaúdeRS / UFRGS; State Secretary of Health of Rio Grande do Sul
• Investigators: Study Chair: Mario R Alvares-da-Silva, PhD, Hospital de Clínicas de Porto Alegre

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2019
• Primary Completion (Actual): December 16, 2020
• Study Completion (Anticipated): November 1, 2021

Study Registration Dates

• First Submitted: July 30, 2019
• First Submitted That Met QC Criteria: July 30, 2019
• First Posted (Actual): July 31, 2019

Study Record Updates

• Last Update Posted (Actual): August 25, 2021
• Last Update Submitted That Met QC Criteria: August 24, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Telemedicine; Hepatitis C; Public Health; Direct acting antivirals
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Anti-Infective Agents; Antiviral Agents; Sofosbuvir; Sofosbuvir-velpatasvir drug combination; Velpatasvir
• Other Study ID Numbers: 2018-0290; Plataforma Brasil (CAAE) (Other Identifier: 91278418200005327)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We plan to open data that might be useful for policy makers, specially in Brazil, and for researchers interested in replicate the study.
• IPD Sharing Time Frame: starting after the publication
• IPD Sharing Access Criteria: Researchers or public health policy makers interested in perform analyses to replicate the study or protocol of telemonitoring.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No