Track topics on Twitter Track topics that are important to you
Hepatitis C is a major cause of liver disease in the United States and leads to cirrhosis of the liver in approximately one-third of patients some of whom will ultimately suffer from liver failure or liver cancer. At present, the recommended therapy of hepatitis C is the combination of alpha interferon and ribavirin given for 6 to 12 months. Ribavirin is a antiviral drug that is given by mouth. Interferon is both an antiviral and an immune medication which must be given by injections (three times a week) and has many difficult side effects. The purpose of this study is to determine whether the combination of ribavirin and interferon improve the liver disease of hepatitis C and whether improvements can be maintained by continuing ribavirin therapy long-term. This study will take 100 to 120 patients suffering from hepatitis C and place them under combination drug therapy with alpha interferon and ribavirin. The course of drug therapy is scheduled to last 6 to 12 months. Patients will be selected after appropriate screening for hepatitis C virus and elevated liver enzymes are conducted and liver biopsy shows chronic hepatitis with some degree of injury and scarring.
During the first 6 months of the study, subjects will be asked to return to the outpatient clinic for routine check-ups and blood tests every 2 to 4 weeks. Blood tests will include tests for hepatitis C virus. If the virus test becomes negative on treatment, the therapy will be considered successful and will be continued for a full 6 or 12 months (depending upon the strain of virus).
If the virus test does not become negative during the first six months of treatment, subjects will be considered "non-responders" and will stop taking interferon but will continue on ribavirin alone or an identically appearing placebo tablet. These non-responsive subjects will continue this therapy for an additional 12 months. (A year-and-a-half total).
Upon completion of the drug therapies, subjects will be requested to submit blood samples and undergo a liver biopsy to determine if the therapy was successful. Test results that reveal a loss of hepatitis C antibodies or normal levels of liver enzymes will be deemed successful.
Patients that have successful laboratory test results will be considered for continuation of ribavirin therapy. Patients that received placebo for a year will be eligible to receive ribavirin long-term at the end of the study.
Between 60 and 90 patients with chronic hepatitis C will be enrolled in a study of the combination of alpha interferon and ribavirin for 12 months with early discontinuation of therapy and randomization to receive either ribavirin alone or placebo for patients who do not respond within 6 months of starting therapy. Adult patients will be chosen who have chronic hepatitis C, HCV RNA in serum, and elevations in serum aminotransferases. Patients who have received alpha interferon in the past will be eligible if they did not have a sustained response to their previous course of interferon. After medical evaluation and liver biopsy, patients will begin receiving alpha interferon by subcutaneous injection in a dose of 3 million units three times weekly. At the same time, patients will begin receiving ribavirin orally in a dose of 1000 mg (if body weight is less than 75 kg) or 1200 mg daily (two or three capsules of 200 mg twice daily). During the initial 24-week period of combination therapy, patients will be seen in the outpatient clinic for medical interview, physical examinations and blood tests at 2 to 4 week intervals. At 24 weeks, patients will be classified as either responders or non-responders based upon HCV RNA testing of serum. Responders will continue on the combination therapy for another 24 weeks (total treatment = 48 weeks). Non-responders will stop interferon therapy and will be randomized to receive either ribavirin or identically appearing placebo capsules for 48 weeks (total treatment = 72 weeks). At the 72 week point (18 months after enrollment), all patients will be readmitted for repeat medical evaluation and liver biopsy. At this point, ribavirin and placebo will be stopped (unless the patient has had a clear histological and biochemical response to therapy) and patients will be monitored with outpatient visits at 8 week intervals for another 6 months.
Patients who exhibit a histological and biochemical response to ribavirin monotherapy will be offered a one-year extension of treatment with ribavirin in a gradually reduced dosage. These patients will be monitored at 8 week intervals and the dose will be reduced by 200 mg per day every 16 weeks to a minimum dose of 600 mg per day. If the biochemical response is maintained, patients will continue on therapy for one year and then undergo repeat medical evaluation and liver biopsy. Continued therapy with ribavirin after this point will depend upon whether safety and efficacy of ribavirin have been demonstrated and whether ribavirin has been approved for use in hepatitis C.
The primary criterion for success of therapy overall will be sustained loss of HCV RNA as assessed at 18 months. Primary criteria for response among the patients who are randomized to receive ribavirin or placebo will be degree of histological improvement on liver biopsy. Secondary criteria will be normalization of ALT levels. This study will allow for therapy of all patients with chronic hepatitis C with the combination of alpha interferon and ribavirin and will allow for therapy of patients with resistant forms of chronic hepatitis C with ribavirin alone and will address whether monotherapy with ribavirin can sustain these improvements and whether the biochemical improvements reflect amelioration of the underlying liver disease as judged histologically.
Endpoint Classification: Efficacy Study, Primary Purpose: Treatment
Chronic Hepatitis C
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institutes of Health Clinical Center (CC)
Published on BioPortfolio: 2014-08-27T03:59:26-0400
The purpose of this study is to confirm if IFN alfa-2b XL has a better antiviral activity and tolerability as compared with current marketed reference, while combined with ribavirin, in a ...
Genotype 4 is the least-studied hepatitis C virus genotype and was considered a difficult to treat genotype due to the disappointing response of chronic hepatitis C genotype 4 to conventio...
This purpose of this study is to determine the safety and effectiveness of viramidine to ribavirin in chronic hepatitis C patients who have never before recieved treatment.
Optimal ribavirin dosages are essential in achieving SVR (sustained virological response). Several studies have shown higher SVR rates in patients receiving higher doses of ribavirin. Ther...
Combination of PEG interferon and ribavirin is the standard treatment of chronic hepatitis C. Efficacy of this treatment has never been evaluated in HCV-HIV infected patients, who have pre...
HEV infection can lead to chronic hepatitis in immunosuppressed patients; extrahepatic manifestations are rarely seen. Here, we report a 13-year-old renal transplant patient with chronic hepatitis E a...
Hepatitis E virus (HEV) is the most common cause of viral hepatitis worldwide. Genotypes 1 and 2 (GT1 and GT2) are mainly present in developing countries, while GT3 and GT4 are prevalent in developed ...
Clinical studies evaluating the efficacy of daclatasvir (DCV) for treatment of chronic hepatitis C virus (HCV) genotype 4 (GT4) infection are scarce. This study aims to evaluate the efficacy and safet...
Some individuals with hepatitis C virus infection treated with direct-acting antivirals require ribavirin to maximize sustained virologic response rates. We describe the clinical management of ribavir...
Japanese patients with chronic hepatitis C virus (HCV) genotype 2 infection have high rates of sustained virologic response (SVR) following 12 weeks of treatment with the nucleotide polymerase inhibit...
INFLAMMATION of the LIVER in humans that is caused by HEPATITIS C VIRUS lasting six months or more. Chronic hepatitis C can lead to LIVER CIRRHOSIS.
INFLAMMATION of the LIVER with ongoing hepatocellular injury for 6 months or more, characterized by NECROSIS of HEPATOCYTES and inflammatory cell (LEUKOCYTES) infiltration. Chronic hepatitis can be caused by viruses, medications, autoimmune diseases, and other unknown factors.
INFLAMMATION of the LIVER in humans caused by HEPATITIS DELTA VIRUS in conjunction with HEPATITIS B VIRUS and lasting six months or more.
A closely related group of antigens found in the plasma only during the infective phase of hepatitis B or in virulent chronic hepatitis B, probably indicating active virus replication; there are three subtypes which may exist in a complex with immunoglobulins G.
A defective virus, containing particles of RNA nucleoprotein in virion-like form, present in patients with acute hepatitis B and chronic hepatitis. It requires the presence of a hepadnavirus for full replication. This is the lone species in the genus Deltavirus.
Astroesophageal Reflux Disease (GERD) Barrett's Esophagus Celiac Disease Cholesterol Crohn's Disease Gastroenterology Hepatitis Hepatology Irritable Bowel Syndrome (IBS) Pancreatitis Peptic Ulcer Disease...
Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...