Hepatitis C VirusPhase 4COPILOTNCT00179413
Study of Long-term Peg Intron vs. Colchicine in Non-responders.
A Phase 4 study testing PEG -Intron and Colchicine in people with Hepatitis C Virus and Advanced Fibrosis, run by Beth Israel Deaconess Medical Center at 49 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatitis C Virus, Advanced Fibrosis, Cirrhosis
- What is being tested?
- PEG -Intron and Colchicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 549 participants
- Where
- 49 sitesUnited States
- Study dates
- 15 Jan 2000to 3 Mar 2010
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- *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.
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
49 sites in 1 country.
49 sites in 1 country
United States49 sites
Austin Gastroenterology
Austin, Texas, 78745
34th Street Community Health Center
Bakersfield, California, 93301-1645
Digestive Disease Associates
Baltimore, Maryland, 21229
Birmingham Gastroenterology Associates
Birmingham, Alabama, 35209
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Bach and Godofsky Infectious Disease
Bradenton, Florida, 34205
Lahey Clinic
Burlington, Massachusetts, 01805
Danbury Hospital
Danbury, Connecticut, 06810
University of Colorado Health Sciences Center
Denver, Colorado, 80220
Wayne State University/Haper Hospital
Detroit, Michigan, 48601
Digestive Health Services
Downers Grove, Illinois, 60515
VA New Jersey Healthcare System
East Orange, New Jersey, 07018
Atlantic Gastroenterology
Egg Harbor, New Jersey, 08234
Hampshire Gastroenterology
Florence, Massachusetts, 01062
Florham Park Endoscopy Center
Florham Park, New Jersey, 07932
Dr. Sam Moskowitz, MD, PC
Forest Hills, New York, 11375
G.I. and Liver Associates
Granbury, Texas, 76048
Southern Clinical Research Consultants
Hollywood, Florida, 33021
Gastroenterology Associates
Kansas City, Missouri, 64131
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
UAMS Medical Center
Little Rock, Arkansas, 72205
Bruce Stein, MD
Manchester, Connecticut, 06040
Medical Center of Wisconsin
Milwaukee, Wisconsin, 53226
Gastroenterology Division Veterans Affairs Medical Center
Minneapolis, Minnesota, 55417
Nashville Gastroenterology Specialists Incorporated
Nashville, Tennessee, 37211
Connecticut Gastroenterology Consultants
New Haven, Connecticut, 06510
Liberty Medical, LLP
New York, New York, 10003
Metro Medical
New York, New York, 10011
Columbia University
New York, New York, 10032
Temple University Hospital
Philadelphia, Pennsylvania, 19140
Albert Einstein Medical Center
Philadelphia, Pennsylvania, 19141
Minnesota Gastroenterology
Plymouth, Minnesota, 55446
Peter Varunok, MD
Poughkeepsie, New York, 12601
University Gastroenterologists
Providence, Rhode Island, 02905
Roger Williams Medical Center
Providence, Rhode Island, 02908
Mayo Clinic
Rochester, Minnesota, 55905
UC Davis Medical Center
Sacramento, California, 95817
Kaiser Permanende-GI Department
Sacramento, California, 95825
Health Science Center
Salt Lake City, Utah, 84132
Digestive Disease Center
San Antonio, Texas, 78205
Texas Transplant Institute
San Antonio, Texas, 78229
Gastroenterology Associates
San Diego, California, 92115
Northern New Mexico Gastroenterology
Santa Fe, New Mexico, 87505
Guthrie Research Foundation
Sayre, Pennsylvania, 18840
Gastroenterology Associates of South Florida
South Miami, Florida, 33143
Upstate Medical Center
Syracuse, New York, 13210
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007-2197
Walter Reed Army Medical Center
Washington D.C., District of Columbia, 20307-5001
Fallon Clinic
Worcester, Massachusetts, 01608
About this study
Official title: Phase IV Study of Long Term Peg-Intron for Patients Who Have Failed to Respond to Rebetron/Interferon With Advanced Fibrosis and Cirrhosis Secondary to Hepatitis C- The Copilot Trial
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.
Read the 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
- Being tested
- PEG -Intron, Colchicine
- Keywords
- hepatitis C, cirrhosis, interferon, colchicine
- Medical subject headings
- Hepatitis C, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PEG -IntronDrug
Also called PEG interferon Alfa-2b 0.5mcg/kg weekly
ColchicineDrug
0.6mg twice a day
| Study group | Role | What they receive |
|---|---|---|
| PEG-Intron | Active comparator | PEG-Intron 0.5mcg/kg once a week SC Receives: Drug: PEG -Intron |
| Colchicine | Active comparator | 0.6mg twice a day Receives: Drug: Colchicine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of the Effect of PEG-Intron 0.5mg Per kg Weekly sc Versus Colchicine 0.6mg Bid Daily on:
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
Measured: 4 years
Secondary outcomes (2)
Evaluation of Safety and Tolerability of Long Term Maintenance PEG-Intron in Patients With Cirrhosis
Defined as the number of patients who discontinued therapy due to an adverse event side
Measured: 4 years
Development of Portal Hypertension
Number of patients who develop endoscopic evidence of varices over 4 year period
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2005 (estimated)
- Study start15 Jan 2000
- Primary completion31 Dec 2009
- Study completion3 Mar 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatitis C VirusStudies of the same condition, open and under way.
- More trials run by Beth Israel Deaconess Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 549 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Schering-Plough
- Responsible party
- Principal investigator, Nezam H. Afdhal, Beth Israel Deaconess Medical Center
- Investigators
- Nezam H Afdhal, MD, Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00179413
- Sponsor's protocol ID
- 2001P000002
- Acronym
- COPILOT
- Status last verified
- Jun 2017
- First submitted
- 10 Sep 2005
- Last updated
- 11 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IV Study of Long Term Peg-Intron for Patients Who Have Failed to Respond to Rebetron/Interferon With Advanced Fibrosis and Cirrhosis Secondary to Hepatitis C- The Copilot Trial
- ClinicalTrials.gov ID
- NCT00179413
- Acronym / sponsor ID
- COPILOT / 2001P000002
- Conditions
- Hepatitis C Virus, Advanced Fibrosis, Cirrhosis
- Keywords
- hepatitis C, cirrhosis, interferon, colchicine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 549 participants (actual)
- Lead sponsor
- Beth Israel Deaconess Medical CenterUniversity, hospital or other
- Collaborators
- Schering-Plough
- Study start
- 15 Jan 2000 (actual)
- Primary completion
- 31 Dec 2009 (actual)
- Study completion
- 3 Mar 2010 (actual)
- First posted
- 16 Sep 2005 (estimated)
- Results
- Posted 11 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PEG-Intron | Active comparator | Drug: PEG -IntronPEG-Intron 0.5mcg/kg once a week SC |
| Colchicine | Active comparator | Drug: Colchicine0.6mg twice a day |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- *Adult male or female, age 18 to 75 years
- 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
Key exclusion criteria (32 listed)
- Any cause of liver disease based on patient history and biopsy (where applicable) other than chronic hepatitis C including but not limited to:
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PEG -IntronAlso: PEG interferon Alfa-2b 0.5mcg/kg weekly | Drug | PEG-Intron |
| Colchicine0.6mg twice a day | Drug | Colchicine |
Primary outcome
Determination of the Effect of PEG-Intron 0.5mg Per kg Weekly sc Versus Colchicine 0.6mg Bid Daily on:
Time frame: 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
2 secondary outcomes
Evaluation of Safety and Tolerability of Long Term Maintenance PEG-Intron in Patients With Cirrhosis
Time frame: 4 years
Development of Portal Hypertension
Time frame: 4 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nezam H Afdhal, MD principal investigator
Beth Israel Deaconess Medical Center
49 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing PEG -Intron and Colchicine in people with Hepatitis C Virus and Advanced Fibrosis, run by Beth Israel Deaconess Medical Center at 49 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 49 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determination of the Effect of PEG-Intron 0.5mg Per kg Weekly sc Versus Colchicine 0.6mg Bid Daily on: (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2017.