People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
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|ClinicalTrials.gov Identifier: NCT03520660|
Recruitment Status : Recruiting
First Posted : May 11, 2018
Last Update Posted : January 5, 2022
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.
To study the course and complications of liver disease after cure of hepatitis C infection.
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
Participants will be screened with:
Blood and urine tests
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
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.
|Condition or disease||Intervention/treatment||Phase|
|Diabetes Mellitus Hepatitis C, Chronic Cardiovascular Diseases||Drug: Epclusa||Phase 4|
We intend to enroll up to 350 subjects with chronic hepatitis C virus (HCV) infection. Subjects will be recruited from two sources:
Phase I: treatment naive or experienced who have failed a prior treatment (including DAA-experienced) who are willing to undergo a pre-treatment liver biopsy.
Subjects yet to achieve an SVR will receive 12 weeks of therapy with sofosbuvir/velapatasvir (Epclusa ) fixed dose combination
Subjects yet to achieve SVR with evidence of clinical cirrhosis will undergo a transjugular liver biopsy with hepatic venous portal gradient (HVPG) pressure measurements in lieu of the percutaneous liver biopsy
Phase II: subjects who have already achieved sustained virologic response (SVR) with oral direct-acting antiviral agent (DAA) only regimen and who have undergone a liver biopsy prior to therapy and no history of hepatic decompensation or hepatocellular carcinoma.
Subjects who have attained an SVR prior to enrollment (or upon achieving an SVR24 in Phase I) will undergo a thorough medical evaluation:
Thereafter, subjects will be followed prospectively every 24 weeks for liver decompensation (ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, variceal hemorrhage), hepatocellular carcinoma, liver-related mortality and all-cause mortality. During each study visit, subjects will be questioned on the development of these adverse outcomes. In addition, blood will be drawn for the assessment of routine blood tests, quantitative viral biomarker levels, serological response markers and immune cell functional status. Blood, urine and stool will be collected and stored for exploratory biomarker development. Fibroscan will be performed annually in all subjects. For subjects with cirrhosis, esophagogastroduodenoscopy (EDG) will be performed annually and imaging every 24 weeks. At the end of 240 weeks, all subjects will be admitted for a liver biopsy to assess the stage of liver fibrosis. In subjects with cirrhosis at study entry, the liver biopsy will be performed by the transjugular route with hepatic venous portal gradient (HVPG) pressure measurements.
The primary goal of the study will be to describe the outcome of viral eradication following treatment with direct acting antiviral agents, to identify predictors of adverse outcomes after sustained viral eradication and regression of fibrosis/cirrhosis.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||450 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Long-Term Follow-Up Of Subjects With CHC Who Achieved A Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents|
|Actual Study Start Date :||October 19, 2018|
|Estimated Primary Completion Date :||December 31, 2032|
|Estimated Study Completion Date :||December 31, 2032|
Experimental: Phase I
Phase I treatment
sofosbuvir/velapatasvir combination (Epclusa)
No Intervention: Phase II after Phase I
Participants who achieved SVR12 in Phase I
No Intervention: Phase II without Phase I
Participants who achieved SVR 24 previously
- Phase II: Liver-related clinical outcome, HCC, or liver-related mortality [ Time Frame: 480 Weeks ]Composite of ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, variceal hemorrhage, hepatocellular carcinoma, liver-related mortality
- Phase I - SVR 12 [ Time Frame: 24 weeks ]SVR at 12 weeks after completion of 12 weeks of treatment
- Phase II: all-cause mortality [ Time Frame: 480 weeks ]
- Phase II: HCC [ Time Frame: 480 weeks ]
- Phase II: Change in Ishak fibrosis score [ Time Frame: 480 weeks ]
- Phase II: Change in Fibroscan [ Time Frame: 480 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03520660
|Contact: Steffan L Cooper||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Marc G Ghany, M.D.||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|