Cardiovascular Diseases Clinical Trial
Official title:
Long-Term Follow-Up Of Subjects With CHC Who Achieved A Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Background: Chronic hepatitis C infects the liver. It may scar the liver. This is called cirrhosis and may lead to liver cancer or death. Current chronic hepatitis C treatments cure most people. But some keep getting complications even after it is cured. Researchers want to study why. Objective: To study the course and complications of liver disease after cure of hepatitis C infection. Eligibility: Adults 18 years and older infected with chronic hepatitis C virus who were never treated or were treated and not cured and those who were cured Design: Participants will be screened with: Blood and urine tests Questionnaires Liver ultrasound Fibroscan. A probe vibrates the liver, testing stiffness. In Phase 1, people with chronic hepatitis C will: Have a 3-day hospital admission to repeat some screening tests and have a liver biopsy. A small piece of liver is removed by needle passed through the skin. Take 1 tablet containing 2 hepatitis C drugs once a day for 12 weeks. Repeat some blood tests at 3 visits in those 12 weeks while on treatment, then 4 additional visits in the next 24 weeks with more blood work collected. Phase 1 participants who test negative for hepatitis C and all other eligible participants will enter Phase 2. Phase 2 participants will have a visit every 24 weeks for 10 years. These may include: Repeats of screening tests Questionnaires Scans Stool tests Chest x-ray Heart function test Endoscopy. A tube guides a camera into the upper digestive system. At about 5 years, participants will have another liver biopsy. Some participants will give separate consent for genetic testing and a special blood procedure.
Status | Recruiting |
Enrollment | 350 |
Est. completion date | December 31, 2032 |
Est. primary completion date | December 31, 2032 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 120 Years |
Eligibility | - INCLUSION CRITERIA: Phase I Treatment - Male or female >= 18 years of age - Either treatment naive or experienced defined as failure of a prior course of interferon-based and ribavirin, DAA plus interferon and DAA only - Confirmation of chronic HCV infection documented by: - A positive HCV RNA or positive HCV genotyping test at least 6-months prior to the Baseline/Day 1 visit - A liver biopsy performed prior to screening visit showing evidence of chronic hepatitis. - Subjects must have the following laboratory parameters at screening: - ALT <= 10 x the upper limit of normal (ULN) - AST <= 10 x ULN - Total bilirubin <2.5 mg/dL, Direct bilirubin <= 1.5 ULN - Platelets >= 50,000 K/mm^3 - HbA1c <= 8.5% - Hemoglobin >= 10g/dL - Albumin >= 3g/dL - INR <= 1.5 unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR. - HCV RNA positive at screening. - Subjects must be of generally good health, with the exception of chronic HCV infection, as determined by the Investigator. Phase II Follow-up - Male or female >= 18 years of age. - SVR24 following therapy with a direct acting antiviral agent regimen and available liver biopsy performed prior to treatment. - Subject must be of generally good health as determined by the Investigator. EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: Phase I Treatment - Pregnancy or lactation - Inability to practice one form of adequate contraction for females of childbearing potential - Prior treatment with a NS5a agent - Current or prior history of any of the following: - Clinically significant illness (other than HCV) or any other major medical disorder that may interfere with subject treatment, assessment, or compliance with the protocol; subjects currently under evaluation for a potentially clinically significant illness (other than HCV) are also excluded - Gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug - Decompensated liver disease as defined by serum bilirubin >= 2.5 mg/dL (with direct bilirubin >= 1.5 mg/dL), INR >1.5 a serum albumin of less than 3 g/dL, or a history of ascites, hepatorenal syndrome, variceal bleeding, or hepatic encephalopathy - Solid organ transplantation - Significant pulmonary disease, significant cardiac disease - History of malignancy or treatment for a malignancy within the past 3 years that is associated with a life expectancy <5 years (except adequately treated carcinoma in situ or basal cell carcinoma of the skin). - Chronic liver disease of a non-HCV etiology with the exception of steatosis (e.g., chronic hepatitis B, hemochromatosis, Wilson s disease, alfa-1 antitrypsin deficiency, cholangitis). - Evidence of harmful or hazardous drinking as defined as a score >= 8 on the AUDIT questionnaire. - Co-infection with HIV defined as the presence of anti-HIV in serum. - Clinically relevant drug abuse based on patient history within 12 months of screening. - Use of medications contraindicated with use of sofosbuvir/velpatasvir within 21 days of the Baseline/Day 1 visit; this washout period does not apply to proton pump inhibitors, which can be taken up to 7 days before baseline Day 1 for the following: - Acid reducing Agents - Antiarrhythmics - Anticancer - Antimycobacterial - HIV antivirals - Herbal supplements - HMG-CoA Reductase Inhibitors - Use of antiviral medications within the last 30 days. - Chronic use of systemically administered immunosuppressive agents (e.g., prednisone equivalent >= 10 mg/day). - Known hypersensitivity to sofosbuvir and velpatasvir, or formulation excipients. - Hepatocellular carcinoma, or the presence of a mass on imaging studies of the liver that is suggestive of hepatocellular carcinoma, or an alpha-fetoprotein level of greater than 500 mg/mL - Active psychiatric problems such as major depression, schizophrenia, bipolar illness, obsessive-compulsive disorder, severe anxiety, or personality disorder that, in the investigator s opinion, might interfere with participation in the study. - Presence of conditions that, in the opinion of the investigators, would not allow the subject to n the current study for at least 1 year. Phase II Follow-up - Pregnancy - Current or prior history of any of the following: - Clinically significant illness (other than resolved HCV) or any other major medical disorder that may interfere with subject treatment, assessment, or compliance with the protocol; subjects currently under evaluation for a potentially clinically significant illness (other than HCV) are also excluded --Decompensated liver disease as defined by serum bilirubin >= 2.5 mg/dL (with direct bilirubin >= 1.5 mg/dL), INR >1.5 a serum albumin of less than 3 g/dL, or a history of ascites, hepatorenal syndrome, variceal bleeding, or hepatic encephalopathy. - Solid organ transplantation - Significant pulmonary disease, significant cardiac disease - History of malignancy or treatment for a malignancy within the past 3 years that is associated with a life expectancy <5 years (except adequately treated carcinoma in situ or basal cell carcinoma of the skin) - Chronic liver disease with the exception of steatosis (e.g., chronic hepatitis B, hemochromatosis, Wilson s disease, alfa-1 antitrypsin deficiency, cholangitis) - Evidence of harmful or hazardous drinking as defined as a score >= 8 on the AUDIT questionnaire - Co-infection with HIV defined as the presence of anti-HIV in serum - Clinically relevant drug abuse based on patient history within 12 months of screening - Chronic use of systemically administered immunosuppressive agents (e.g., prednisone equivalent >= 10 mg/day) - Hepatocellular carcinoma, or the presence of a mass on imaging studies of the liver that is suggestive of hepatocellular carcinoma, or an alpha-fetoprotein level of greater than 500 mg/mL - Active psychiatric problems such as major depression, schizophrenia, bipolar illness, obsessive-compulsive disorder, severe anxiety, or personality disorder that, in the investigator s opinion, might interfere with participation in the study - Presence of conditions that, in the opinion of the investigators, would not allow the patient to be followed in the current study for at least 1 year. |
Country | Name | City | State |
---|---|---|---|
United States | National Institutes of Health Clinical Center | Bethesda | Maryland |
Lead Sponsor | Collaborator |
---|---|
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Phase II: Liver-related clinical outcome, HCC, or liver-related mortality | Composite of ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, variceal hemorrhage, hepatocellular carcinoma, liver-related mortality | 480 Weeks | |
Primary | Phase I - SVR 12 | SVR at 12 weeks after completion of 12 weeks of treatment | 24 weeks | |
Secondary | Phase II: All-cause mortality | 480 weeks | ||
Secondary | Phase II: Change in Fibroscan | 480 weeks | ||
Secondary | Phase II: Assess Regression in Portal Hypertension | 480 weeks | ||
Secondary | Phase II: HCC | 480 weeks | ||
Secondary | Phase II: Change in Ishak fibrosis score | 480 weeks |
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