Study of Nitazoxanide, Peginterferon Alfa-2a and Ribavirin for the Treatment of Hepatitis C
- Conditions
- Chronic Hepatitis C
- Interventions
- Registration Number
- NCT00495391
- Lead Sponsor
- Romark Laboratories L.C.
- Brief Summary
The purpose of this study is to determine if nitazoxanide in combination with peginterferon alfa-2a and ribavirin is safe and effective in treating chronic hepatitis C in patients that have previously failed to respond to treatment with peginterferon and ribavirin.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 64
- Chronic hepatitis C genotype 1.
- Failed to respond to ≥12 weeks of peginterferon and ribavirin (<2 log10 drop in Hepatitis C Virus Ribonucleic Acid (HCV RNA) at week 12 or detectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) at week 24).
- Females of child-bearing age who are either pregnant, breast-feeding or not using birth control and are sexually active.
- Males whose female partners are either pregnant or of child-bearing potential or not using birth control and are sexually active.
- Other causes of liver disease including autoimmune hepatitis.
- Transplant recipients receiving immune suppression therapy.
- Screening tests positive for Anti-Hepatitis A Virus Immunoglobulin M Antibody (anti-HAV IgM Ab), Hepatitis B's antigen (HBsAg), Anti-Hepatitis B core antigen Immunoglobulin M Antibody (anti-HBc IgM Ab) or Anti-Human Immunodeficiency Virus Antibody (anti-HIV Ab).
- Decompensated cirrhosis, history of variceal bleeding, ascites, hepatic encephalopathy, Child-Turcotte-Pugh (CTP) score >6 or Model for End-stage Liver Disease (MELD) score >8.
- Alcohol consumption of >40 grams per day or an alcohol use pattern that will interfere with the study.
- Absolute neutrophil count <1500 cells/mm3; platelet count <135,000 cells/mm3; hemoglobin <12 g/dL for women and <13 g/dL for men; or serum creatinine concentration ≥1.5 times Upper Limit of Normal (ULN).
- Hypothyroidism or hyperthyroidism not effectively treated with medication.
- Hemoglobin A1C (HgbA1c) >7.5 or history of diabetes mellitus.
- Body Mass Index (BMI) >28.
- History or other clinical evidence of significant or unstable cardiac disease.
- History or other clinical evidence of chronic pulmonary disease associated with functional impairment.
- Serious or severe bacterial infection(s).
- Ulcerative or hemorrhagic/ischemic colitis.
- Pancreatitis.
- History of severe or uncontrolled psychiatric disease, including severe depression, history of suicidal ideation, suicidal attempts or psychosis requiring medication and/or hospitalization.
- History of uncontrolled severe seizure disorder.
- Requires concomitant theophylline or methadone.
- History of immunologically mediated disease requiring more than intermittent anti-inflammatory medications for management or that requires frequent or prolonged use of corticosteroids.
- History or other evidence of severe retinopathy or clinically relevant ophthalmological disorder due to diabetes mellitus or hypertension.
- Hemoglobinopathies.
- History of hypersensitivity or intolerance to nitazoxanide or any of the excipients comprising the nitazoxanide tablets, peginterferon alfa-2a injectable solution or ribavirin tablets.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 Peginterferon alfa-2a Oral 500 mg nitazoxanide twice daily for 4 weeks followed by oral 500 mg nitazoxanide twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if \<75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. 1 Ribavirin Oral 500 mg nitazoxanide twice daily for 4 weeks followed by oral 500 mg nitazoxanide twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if \<75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. 2 Placebo Oral placebo twice daily for 4 weeks followed by oral placebo twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if \<75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. 1 Nitazoxanide Oral 500 mg nitazoxanide twice daily for 4 weeks followed by oral 500 mg nitazoxanide twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if \<75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. 2 Peginterferon alfa-2a Oral placebo twice daily for 4 weeks followed by oral placebo twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if \<75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks. 2 Ribavirin Oral placebo twice daily for 4 weeks followed by oral placebo twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if \<75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks.
- Primary Outcome Measures
Name Time Method Sustained Virologic Response (HCV RNA Below Lower Limit of Detection) 24 weeks after end of treatment Hepatitis C Virus Ribonucleic Acid (HCV RNA) below lower limit of detection 24 weeks after the end of treatment. All others were considered non-responders.
- Secondary Outcome Measures
Name Time Method End of Treatment Response (HCV RNA Below Lower Limit of Detection) At end of treatment Hepatitis C Virus Ribonucleic Acid (HCV RNA) below lower limit of detection at the end of treatment. All others were considered non-responders.
Early Virologic Response (HCV RNA Below Lower Limit of Detection) After 12 weeks combination treatment Hepatitis C Virus Ribonucleic Acid (HCV RNA) below lower limit of detection after 12 weeks of combination therapy.
Rapid Virologic Response (HCV RNA Below Lower Limit of Detection) After 4 weeks combination treatment Hepatitis C Virus Ribonucleic Acid (HCV RNA) below lower limit of detection after 4 weeks of combination therapy.
Changes in ALT From baseline to end of follow up This analysis was conducted using a comparison of changes in Alanine aminotransferase (ALT) from baseline through week 8, week 16, end of treatment and end of follow up.
Trial Locations
- Locations (10)
VA Palo Alto Healthcare System
🇺🇸Palo Alto, California, United States
McGuire VA Medical Center
🇺🇸Richmond, Virginia, United States
Nashville Medical Research Institute
🇺🇸Nashville, Tennessee, United States
Stanford University School of Medicine
🇺🇸Stanford, California, United States
University of Florida Hepatology
🇺🇸Gainesville, Florida, United States
Yale University Digestive Diseases
🇺🇸New Haven, Connecticut, United States
Florida Center for Gastroenterology
🇺🇸Largo, Florida, United States
Atlanta Gastroenterology Associates
🇺🇸Atlanta, Georgia, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Brooke Army Medical Center
🇺🇸Fort Sam Houston, Texas, United States