The HALT-C Trial is a National Institute of Diabetes and Digestive and Kidney Diseases sponsored, randomized clinical trial of long-term use of Peginterferon alfa-2a (pegylated interferon) in patients who failed to respond to prior interferon treatment. All patients who enter the trial will be treated for 6 months with Peginterferon alfa-2a and Ribavirin. Patients who respond to this 6 month treatment will continue to be treated for an additional 6 months. Patients who do not respond to this treatment will be eligible for the long-term maintenance phase of this study where patients will be randomly selected to be treated with Peginterferon alfa-2a or to discontinue treatment for 3.5 years. Patients in both arms of this study will be followed closely with quarterly study visits. The combination of peginterferon plus ribavirin has recently been approved by the FDA for treatment of chronic hepatitis C. Patients who remain HCV-RNA positive after being treated for at least 6 months with peginterferon and ribavirin outside of this study may be eligible to directly enter the randomized portion of the HALT-C Trial. The HALT-C study is designed to determine if continuing interferon long-term over several years will suppress Hepatitis C virus, prevent progression to cirrhosis, prevent liver cancer and reduce the need for liver transplantation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
1,050
Peginterferon alfa-2a 180 mcg/week injection, for 24 weeks, plus 1000-1200 mg Ribavirin oral (prescribed according to weight \<75 kg, \>75 kg) daily in two divided doses for 24 weeks
90 mcg/week injection, for 3.5 years
University of California-Irvine/VA Medical Center-Long Beach
Long Beach, California, United States
USC School of Medicine
Los Angeles, California, United States
UCHSC (University of Colorado)
Denver, Colorado, United States
University of Connecticut Health Center
Farmington, Connecticut, United States
Lds, Niddk, Nih
Bethesda, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
UMass Memorial HealthCare, University Campus
Worcester, Massachusetts, United States
University of Michigan
Ann Arbor, Michigan, United States
Saint Louis University
St Louis, Missouri, United States
University of Texas Southwestern - Dallas
Dallas, Texas, United States
...and 1 more locations
Progression of Liver Disease as Indicated by Death, Hepatic Decompensation, Hepatocellular Carcinoma, or for Patients With Noncirrhotic Fibrosis at Baseline, an Increase in the Ishak Hepatic Fibrosis Score of 2 or More Points
Progression of liver disease within 1400 days as indicated by death, hepatic decompensation (variceal hemorrhage; ascites; spontaneous bacterial peritonitis; hepatic encephalopathy), hepatocellular carcinoma, a Child-Turcotte-Pugh (CTP) score of 7 or more on two consecutive study visits (score range 5-15, higher score indicates greater decompensation), or for patients with noncirrhotic fibrosis at baseline, an increase in Ishak hepatic fibrosis score (range 0-6, higher score indicates greater fibrosis) of at least 2 points by assessment of a liver-biopsy specimen obtained during the study
Time frame: 1400 days (3.85 years) post randomization
Increase in Ishak Fibrosis Score by 2 Points or More at 2 or 4 Year Biopsies
For patients with noncirrhotic fibrosis at baseline, an increase in Ishak hepatic fibrosis score (range 0-6, higher score indicates greater fibrosis) of at least 2 points by assessment of a liver-biopsy specimen obtained during the study (collected at Year 2 and Year 4 biopsies, 1.5 and 3.5 years after randomization)
Time frame: 1400 days (3.85 years) post randomization
Death From Any Cause
Time frame: 1400 days (3.85 years) post randomization
Development of Hepatocellular Carcinoma (HCC)
A diagnosis of development of hepatocellular carcinoma (HCC) was based on either 1. Histology showing HCC (from a biopsy, surgery, or autopsy) or 2. A new hepatic defect on imaging with an alpha-fetoproteion (AFP) level rising to \> 1,000 ng/ml.
Time frame: 1400 days (3.85 years) post randomization
Child-Turcotte-Pugh (CTP) Score of 7 or Higher at Two Consecutive Study Visits
Child-Turcotte-Pugh (CTP) score of 7 or more on two consecutive study visits (score range 5-15, higher score indicates greater hepatic decompensation)
Time frame: 1400 days (3.85 years) post randomization
Variceal Hemorrhage
A gastrointestinal hemorrhage which is believed by the investigator to be due to bleeding esophageal or gastric varices. In general, an endoscopy will have been performed and will have revealed either direct evidence of variceal bleeding (bleeding varix, red wale sign) or historical evidence for significant upper gastro-intestinal bleeding plus upper endoscopy revealing moderate varices and no other site of bleeding is identified
Time frame: 1400 days (3.85 years) post randomization
Ascites
Any abdominal fluid which is: 1. Mild, moderate or marked on ultrasound; or 2. Progressive on serial physical examinations; or 3. Requires diuretic therapy. To meet the definition of ascites, abdominal fluid that is "mild" ("barely detectable") on physical examination requires ultrasound confirmation that is "mild", "moderate" or "marked" ascites. Ultrasound reports of minimal fluid around the liver do not meet the definition.
Time frame: 1400 days (3.85 years) post randomization
Spontaneous Bacterial Peritonitis
Any episode of spontaneous ascitic infection diagnosed on the basis of elevated neutrophil count (\> 250/ml) in paracentesis fluid or positive bacterial cultures and clinical diagnosis in the absence of white blood cell (WBC) availability.
Time frame: 1400 days (3.85 years) post randomization
Hepatic Encephalopathy
Any mental status alteration which is deemed by the investigator to be due to portosystemic encephalopathy, whether occurring during a provoked episode (GI bleeding, diuretics, usual sedative doses), or spontaneously (without apparent cause).
Time frame: 1400 days (3.85 years) post randomization
Serious Adverse Events
A serious adverse event (SAE) is an untoward medical occurrence that results in any of the following: 1. Death 2. Is life threatening (risk of death at the time of the event) 3. Requires in-patient hospitalization or prolongation of existing hospitalization 4. Results in persistent or significant disability/incapacity 5. Congenital abnormality or birth defect Trial outcomes (except death) were not considered serious adverse events.
Time frame: 1400 days (3.85 years) post randomization
Changes in Fibrosis From Baseline at Year 2 or Year 4 Biopsy.
Change in Ishak hepatic fibrosis score (range 0-6, higher score indicates greater fibrosis) by assessment of a liver-biopsy specimen obtained during the study (collected at baseline, Year 2 and Year 4 biopsies, 1.5 and 3.5 years after randomization)
Time frame: 1400 days (3.85 years) post randomization
Presumed Hepatocellular Carcinoma (HCC)
Presumed HCC was considered when histology was not available and alpha-fetoprotein (AFP) is \<1000 ng/ml, if: 1. A new hepatic lesion was shown on ultrasound and 1 additional imaging showed a hepatic lesion with characteristics of HCC. 2. AFP\> upper limit of normal (ULN) and 2 imaging studies showed a hepatic lesion with characteristics of HCC. 3. A progressively enlarging hepatic lesion starting as a new defect resulting in patient death. 4. A new hepatic defect with at least 1 characteristic scan and: 1. Increase in size over time or 2. Increasing AFP rising to a level of \>200 ng/ml
Time frame: 1400 days (3.85 years) post randomization
SF-36 Vitality Summary Score
Change from baseline to years 0.5, 1.5, 2.5, and 3.5 in Short Form Health Survey (SF-36) Vitality summary score. The SF-36 Vitality summary score is the sum of 4 individual scores. It is scaled from 0 to 100 with a score of 0 equivalent to maximum disability and a score of 100 equivalent to no disability. A negative value indicates a decrease in quality of life from baseline.
Time frame: 0.5, 1.5, 2.5, and 3.5 years after randomization
SF-36 Physical Function Summary Score
Change from baseline to years 0.5, 1.5, 2.5, and 3.5 in Short Form Health Survey (SF-36) Physical Function summary score. The SF-36 Physical Function summary score is the sum of 10 individual scores. It is scaled from 0 to 100 with a score of 0 equivalent to maximum disability and a score of 100 equivalent to no disability. A negative value indicates a decrease in quality of life from baseline.
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Time frame: 0.5, 1.5, 2.5, and 3.5 years after randomization
SF-36 Mental Health Summary Score
Change from baseline to years 0.5, 1.5, 2.5, and 3.5 in Short Form Health Survey (SF-36) Mental Health summary score. The SF-36 Mental Health summary score is the sum of 5 individual scores. It is scaled from 0 to 100 with a score of 0 equivalent to maximum disability and a score of 100 equivalent to no disability. A negative value indicates a decrease in quality of life from baseline.
Time frame: 0.5, 1.5, 2.5, and 3.5 years after randomization