Study of Long-term Peg Intron vs. Colchicine in Non-responders.
- Conditions
- Hepatitis C VirusAdvanced FibrosisCirrhosis
- Interventions
- Registration Number
- NCT00179413
- Lead Sponsor
- Beth Israel Deaconess Medical Center
- Brief Summary
In this study Peg-Intron will be tested to see if it will give better results than Colchicine. At this time, there is currently no recommended maintenance treatment for patients who have failed to respond to Interferon/Rebetron/Peg Intron and have advanced fibrosis. The purpose of this study is to compare two treatments to slow down the progression of liver disease and to prevent liver failure and liver cancer. The treatment will not cure Hepatitis C, but is being evaluated to see if it can slow down disease progression.
- Detailed Description
We are proposing a randomized trial of Peg-Intron 0.5mcg per kg weekly versus colchicine 0.6mg bid in prior non-responders to Interferon, Rebetron, PegIntron, or PegIntron \& Ribavirin or any third agent such as Pegasys, CellCept, Amantadine with advanced fibrosis/cirrhosis. The specific aims of this proposal are to evaluate the role of long term Peg-Intron therapy on the natural history of patients with advanced chronic HCV infection with a primary focus on prevention of hepatic decompensation, progression of fibrosis and hepatoma development.
The study design will focus on 3 monthly clinical evaluation for decompensation of liver function, rigorous clinical screening for development of hepatocellular cancer and liver biopsies for determination of progression of liver fibrosis every second year.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 549
-
*Adult male or female, age 18 to 75 years
-
HCV RNA positive by PCR
-
Previous treatment with at least three months of interferon or interferon / Ribavirin. Patients should have had no interferon for at least 2 months prior to enrollment.
- Non-responders are identified by failure to clear virus by PCR after a minimum 3-month course of treatment and who have been off treatment for at least 2 months with a positive PCR for HCV prior to entry into the current study, 2) Partial responders have a reduction of 1 long in HCV RNA, but the virus is still detectable, 3) Breakthrough patients have been negative on treatment, but virus appeared while still on treatment, 4) Relapsers are defined as negative PCR at some point during treatment, but virus reoccurred or was detectable by HCV PCR when treatment stopped.
-
Patients should have had a liver biopsy showing at least Stage 3 disease prior to being considered for this study. A baseline liver biopsy is necessary for inclusion in the study. Baseline liver biopsies can be performed within six months of entering the study.
In patients with cirrhosis and endoscopic evidence of portal hypertension, a biopsy within the last 2 years is acceptable as the baseline biopsy. For patients with established cirrhosis on liver biopsy and no portal hypertension, a biopsy within 12 months can be used as the baseline biopsy if it is available for evaluation by the Pathology core. All these patients will still require liver biopsy at 2 years and 4 years. The decision to biopsy at 2 and 4 years is also a clinical decision and in the presence of clinical progression or coagulopathy, or where there may be a risk from liver biopsy, the Investigator should call the PI, Dr. Afdhal for a waiver of biopsy. Patients with Ishak Stage 3 and 4 require a biopsy within 6 months of randomization.
- Hemoglobin >= 11 g/dl in males and 10 g/dl in females
- Neutrophil count > 1,500/mm3
- Platelets > 50, 000/mm3
Platelet count: For standard dose of PEG-Intron 0.5mcg/kg platelet count must be greater than 70,000. Patients with platelet count 50 - 70,000 can start at 0.25mcg/kg for weeks 0 - 4. If platelets fall to less than 30,000, stop treatment. If platelets remain > 50,000 at week 4, PEG-Intron can be increased to 0.5mcg/kg. Patients randomized to Colchicine with platelets 50,000 - 70,000 can be started at standard dose 0.6mg bid po with standard dose reduction.
-
Prothrombin time <= 3secs prolonged compared to control or an equivalent INR < 1.5
-
Total bilirubin < 3gm/dL
-
Fasting blood sugar <= 115 mg/dl or within 20% of the upper limit of normal for non-diabetic patients
-
Albumin (> 2.8mg/dl)
-
Serum creatinine < 1.4 mg/dL
-
TSH within the normal range (Patients with thyroid disease who are well controlled are eligible if the remainder of the inclusion/exclusion criteria are met)
-
HIV negative.
- HBsAg negative
- Childs Pugh score of less than or equal to 7
- Serum positive for anti-hepatitis C antibodies or HCV RNA.
- Alpha-fetoprotein < 100ng/ml with ultrasound negative for focal mass or HCC. For any patient with an Alpha-fetoprotein >100 ng/ml either a triple phase contrast CT scan or MRI with gadolinium must show no focal mass or evidence of HCC
- Ultrasound with no evidence of focal mass suggestive of hepatoma (within 6 months of informed consent).
- Documentation that sexually active female patients of childbearing potential are practicing adequate contraception during the treatment period. A urine pregnancy test obtained at entry prior to the initiation of treatment must be negative. Female patients must not be breast-feeding. Documentation that sexually active male patients are practicing acceptable methods of contraception during the treatment period.
- Written informed consent specific for this protocol has been obtained prior to entry.
-
Any cause of liver disease based on patient history and biopsy (where applicable) other than chronic hepatitis C including but not limited to:
- Co-infection with hepatitis B or HIV
- Hemochromatosis (confirmed by genetic testing)
- Alpha-1 antitrypsin deficiency
- Wilson's disease
- Renal or liver transplant patients
- Autoimmune hepatitis
- Alcoholic liver disease
- Obesity induced liver disease
- Drug related liver disease
In addition:
- Evidence of decompensated liver disease such as a history or presence of ascites, and spontaneous encephalopathy. Patients with past bleeding esophageal varices that have not bled for more than 1 year can be included.
- Hypersensitivity to alpha interferon
- Drug related liver disease
- Hemoglobinopathies (e.g. Thalassaemia, sickle cell disease).
- Patients with clinically significant retinal abnormalities.
- Substance abuse, such as alcohol (·> 80 gm/day), I.V. drugs and inhaled drugs. If the patient has a history of substance abuse, to be considered for inclusion into the protocol, the patient must have abstained from using the abused substance for at least 6 months. Patients on methadone will be allowed in the study with no restrictions as is now standard of care in HCV therapy.
- Patients with a history of organ transplantation will be excluded.
Preexisting psychiatric conditions, especially depression, or a history of severe psychiatric disorder, such as major psychoses, suicidal ideation and/or suicidal attempt are excluded. Patients with a history of mild depression may enter the protocol if they meet the following eligibility criterion and are monitored more intensively.
Mild depression: to include either situational depression of a limited period or depressive symptoms, which do not significantly interfere with the patient's work or daily functions.
Any patient with an active manic element to his/her previous symptom complex will be excluded.
Any known pre-existing medical condition that could interfere with the patient's participation in and completion of the study such as:
- Pre-existing psychiatric condition, especially severe depression, or a history of severe psychiatric disorder
- CNS trauma or seizure disorder requiring therapy
- Significant cardiac dysfunction in the previous 6 months e.g. angina, CCF, hypertension or arrhythmia Patients on treatment are eligible as long as they have been symptom free for the previous 6 months.
- Poorly controlled diabetes mellitus
- Chronic pulmonary disease (e.g. COAD)
- Immunologically mediated diseases (e.g. inflammatory bowel disease, SLE, ITP, autoimmune hemolytic anemia, scleroderma, rheumatoid arthritis, severe psoriasis)
- Clinical gout
- Patients with clinically significant retinal abnormalities
- Patients with organ transplants
Any other condition, which in the view of the investigator, would make the patient unsuitable for enrolment, or could interfere with the patient participating in and completing the protocol are included as well.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Colchicine Colchicine 0.6mg twice a day PEG-Intron PEG -Intron PEG-Intron 0.5mcg/kg once a week SC
- Primary Outcome Measures
Name Time Method Determination of the Effect of PEG-Intron 0.5mg Per kg Weekly sc Versus Colchicine 0.6mg Bid Daily on: 4 years number of patients with a liver related outcomes including: mortality, liver transplant, variceal or portal hypertensive bleeding,Development of jaundice, ascites or encephalopathy with an increase in CPT of \> 2 points and development of hepatoma
- Secondary Outcome Measures
Name Time Method Evaluation of Safety and Tolerability of Long Term Maintenance PEG-Intron in Patients With Cirrhosis 4 years Defined as the number of patients who discontinued therapy due to an adverse event side
Development of Portal Hypertension 4 years Number of patients who develop endoscopic evidence of varices over 4 year period
Trial Locations
- Locations (48)
Southern Clinical Research Consultants
🇺🇸Hollywood, Florida, United States
Lahey Clinic
🇺🇸Burlington, Massachusetts, United States
Fallon Clinic
🇺🇸Worcester, Massachusetts, United States
Guthrie Research Foundation
🇺🇸Sayre, Pennsylvania, United States
Birmingham Gastroenterology Associates
🇺🇸Birmingham, Alabama, United States
Wayne State University/Haper Hospital
🇺🇸Detroit, Michigan, United States
Gastroenterology Division Veterans Affairs Medical Center
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Texas Transplant Institute
🇺🇸San Antonio, Texas, United States
Health Science Center
🇺🇸Salt Lake City, Utah, United States
Medical Center of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
UAMS Medical Center
🇺🇸Little Rock, Arkansas, United States
34th Street Community Health Center
🇺🇸Bakersfield, California, United States
Danbury Hospital
🇺🇸Danbury, Connecticut, United States
Georgetown University Medical Center
🇺🇸Washington, D.C., District of Columbia, United States
Walter Reed Army Medical Center
🇺🇸Washington, D.C., District of Columbia, United States
Digestive Disease Associates
🇺🇸Baltimore, Maryland, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Minnesota Gastroenterology
🇺🇸Plymouth, Minnesota, United States
Hampshire Gastroenterology
🇺🇸Florence, Massachusetts, United States
VA New Jersey Healthcare System
🇺🇸East Orange, New Jersey, United States
Atlantic Gastroenterology
🇺🇸Egg Harbor, New Jersey, United States
Metro Medical
🇺🇸New York, New York, United States
Florham Park Endoscopy Center
🇺🇸Florham Park, New Jersey, United States
Peter Varunok, MD
🇺🇸Poughkeepsie, New York, United States
Liberty Medical, LLP
🇺🇸New York, New York, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Columbia University
🇺🇸New York, New York, United States
Upstate Medical Center
🇺🇸Syracuse, New York, United States
University Gastroenterologists
🇺🇸Providence, Rhode Island, United States
Roger Williams Medical Center
🇺🇸Providence, Rhode Island, United States
Nashville Gastroenterology Specialists Incorporated
🇺🇸Nashville, Tennessee, United States
Digestive Disease Center
🇺🇸San Antonio, Texas, United States
G.I. and Liver Associates
🇺🇸Granbury, Texas, United States
Dr. Sam Moskowitz, MD, PC
🇺🇸Forest Hills, New York, United States
Bruce Stein, MD
🇺🇸Manchester, Connecticut, United States
University of Colorado Health Sciences Center
🇺🇸Denver, Colorado, United States
Bach and Godofsky Infectious Disease
🇺🇸Bradenton, Florida, United States
Northern New Mexico Gastroenterology
🇺🇸Santa Fe, New Mexico, United States
Gastroenterology Associates of South Florida
🇺🇸South Miami, Florida, United States
Digestive Health Services
🇺🇸Downers Grove, Illinois, United States
Albert Einstein Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
Austin Gastroenterology
🇺🇸Austin, Texas, United States
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Gastroenterology Associates
🇺🇸Kansas City, Missouri, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
Kaiser Permanende-GI Department
🇺🇸Sacramento, California, United States
Connecticut Gastroenterology Consultants
🇺🇸New Haven, Connecticut, United States