Long Term Interferon for Patients Who Did Not Clear Hepatitis C Virus With Standard Treatment

Phase 3

Completed

Conditions: Chronic Hepatitis c
Hepatic Cirrhosis
Cirrhosis, Liver
Fibrosis, Liver

Interventions: Drug: Peginterferon alfa-2a + Ribavirin
Drug: Peginterferon alfa-2a

Registration Number: NCT00006164

Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1050

Inclusion Criteria

Age at entry at least 18 years.
Positive for Hepatitis C.
Previous treatment with any interferon or interferon and ribavirin for at least 3 months.
Documented non-response to treatment with interferon.
A liver biopsy demonstrating significant liver scarring.

Exclusion Criteria

No other liver disease.
No unstable major medical diseases or conditions.
No major complications of cirrhosis.
No recent abuse of alcohol or illicit drugs.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Peginterferon alfa-2a + Ribavirin	Peg-interferon alfa-2a 90 mcg/week
1	Peginterferon alfa-2a	Peg-interferon alfa-2a 90 mcg/week
2	Peginterferon alfa-2a + Ribavirin	Standard of care followup

Primary Outcome Measures

Name	Time	Method
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	1400 days (3.85 years) post randomization	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
Increase in Ishak Fibrosis Score by 2 Points or More at 2 or 4 Year Biopsies	1400 days (3.85 years) post randomization	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)
Death From Any Cause	1400 days (3.85 years) post randomization
Development of Hepatocellular Carcinoma (HCC)	1400 days (3.85 years) post randomization	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.
Child-Turcotte-Pugh (CTP) Score of 7 or Higher at Two Consecutive Study Visits	1400 days (3.85 years) post randomization	Child-Turcotte-Pugh (CTP) score of 7 or more on two consecutive study visits (score range 5-15, higher score indicates greater hepatic decompensation)
Variceal Hemorrhage	1400 days (3.85 years) post randomization	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
Ascites	1400 days (3.85 years) post randomization	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.
Spontaneous Bacterial Peritonitis	1400 days (3.85 years) post randomization	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.
Hepatic Encephalopathy	1400 days (3.85 years) post randomization	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).

Secondary Outcome Measures

Name	Time	Method
Serious Adverse Events	1400 days (3.85 years) post randomization	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.
Changes in Fibrosis From Baseline at Year 2 or Year 4 Biopsy.	1400 days (3.85 years) post randomization	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)
Presumed Hepatocellular Carcinoma (HCC)	1400 days (3.85 years) post randomization	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
SF-36 Mental Health Summary Score	0.5, 1.5, 2.5, and 3.5 years after randomization	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.
SF-36 Vitality Summary Score	0.5, 1.5, 2.5, and 3.5 years after randomization	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.
SF-36 Physical Function Summary Score	0.5, 1.5, 2.5, and 3.5 years after randomization	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.

Trial Locations

Locations (11): USC School of Medicine
🇺🇸
Los Angeles, California, United States
University of Connecticut Health Center
🇺🇸
Farmington, Connecticut, United States
University of Texas Southwestern - Dallas
🇺🇸
Dallas, Texas, United States
Saint Louis University
🇺🇸
Saint Louis, Missouri, United States
Medical College of Virginia
🇺🇸
Richmond, Virginia, United States
University of California-Irvine/VA Medical Center-Long Beach
🇺🇸
Long Beach, California, United States
UCHSC (University of Colorado)
🇺🇸
Denver, Colorado, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Lds, Niddk, Nih
🇺🇸
Bethesda, Maryland, United States
UMass Memorial HealthCare, University Campus
🇺🇸
Worcester, Massachusetts, United States
University of Michigan
🇺🇸
Ann Arbor, Michigan, United States