Study of Long-term Peg Intron vs. Colchicine in Non-responders.

NCT ID: NCT00179413

Last Updated: 2017-07-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 549 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-01-15
• Study Completion Date: 2010-03-03

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.

Conditions

Hepatitis C Virus; Advanced Fibrosis; Cirrhosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

PEG-Intron

PEG-Intron 0.5mcg/kg once a week SC

Group Type: ACTIVE_COMPARATOR

PEG -Intron

Intervention Type: DRUG

Colchicine

0.6mg twice a day

Group Type: ACTIVE_COMPARATOR

Colchicine

Intervention Type: DRUG

0.6mg twice a day

Interventions

PEG -Intron

Intervention Type: DRUG

Colchicine

0.6mg twice a day

Intervention Type: DRUG

Other Intervention Names

PEG interferon Alfa-2b 0.5mcg/kg weekly

Eligibility Criteria

Inclusion Criteria

• *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.

1. 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

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Schering-Plough

INDUSTRY

Sponsor Role: collaborator

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Nezam H. Afdhal

Professor of Medicine, Part-time

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nezam H Afdhal, MD

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

Locations

Birmingham Gastroenterology Associates

Birmingham, Alabama, United States

UAMS Medical Center

Little Rock, Arkansas, United States

34th Street Community Health Center

Bakersfield, California, United States

UC Davis Medical Center

Sacramento, California, United States

Kaiser Permanende-GI Department

Sacramento, California, United States

Gastroenterology Associates

San Diego, California, United States

University of Colorado Health Sciences Center

Denver, Colorado, United States

Danbury Hospital

Danbury, Connecticut, United States

Bruce Stein, MD

Manchester, Connecticut, United States

Connecticut Gastroenterology Consultants

New Haven, 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

Bach and Godofsky Infectious Disease

Bradenton, Florida, United States

Southern Clinical Research Consultants

Hollywood, Florida, United States

Gastroenterology Associates of South Florida

South Miami, Florida, United States

Digestive Health Services

Downers Grove, Illinois, United States

Digestive Disease Associates

Baltimore, Maryland, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Lahey Clinic

Burlington, Massachusetts, United States

Hampshire Gastroenterology

Florence, Massachusetts, United States

Fallon Clinic

Worcester, Massachusetts, United States

Wayne State University/Haper Hospital

Detroit, Michigan, United States

Gastroenterology Division Veterans Affairs Medical Center

Minneapolis, Minnesota, United States

Minnesota Gastroenterology

Plymouth, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

Gastroenterology Associates

Kansas City, Missouri, United States

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

VA New Jersey Healthcare System

East Orange, New Jersey, United States

Atlantic Gastroenterology

Egg Harbor, New Jersey, United States

Florham Park Endoscopy Center

Florham Park, New Jersey, United States

Northern New Mexico Gastroenterology

Santa Fe, New Mexico, United States

Dr. Sam Moskowitz, MD, PC

Forest Hills, New York, United States

Liberty Medical, LLP

New York, New York, United States

Metro Medical

New York, New York, United States

Columbia University

New York, New York, United States

Peter Varunok, MD

Poughkeepsie, New York, United States

Upstate Medical Center

Syracuse, New York, United States

Temple University Hospital

Philadelphia, Pennsylvania, United States

Albert Einstein Medical Center

Philadelphia, Pennsylvania, United States

Guthrie Research Foundation

Sayre, Pennsylvania, 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

Austin Gastroenterology

Austin, Texas, United States

G.I. and Liver Associates

Granbury, Texas, United States

Digestive Disease Center

San Antonio, Texas, 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

Countries

United States

Other Identifiers

2001P000002

Identifier Type: -

Identifier Source: org_study_id