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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Other: Telemedicine
* Drug: Velpatasvir/Sofosbuvir


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C, Telemedicine, Direct acting antivirals, Public Health