Long Term Interferon for Patients Who Did Not Clear Hepatitis C Virus With Standard Treatment (HALT-C)

April 29, 2020 updated by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Hepatitis C Antiviral Long-term Treatment Against Cirrhosis Trial (HALT-C)

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 Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

1050

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Long Beach, California, United States, 90822
        • University of California-Irvine/VA Medical Center-Long Beach
      • Los Angeles, California, United States, 90033
        • Usc School Of Medicine
    • Colorado
      • Denver, Colorado, United States, 80262
        • UCHSC (University of Colorado)
    • Connecticut
      • Farmington, Connecticut, United States, 06030
        • University of Connecticut Health Center
    • Maryland
      • Bethesda, Maryland, United States, 20892-1800
        • Lds, Niddk, Nih
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Worcester, Massachusetts, United States, 01655
        • UMass Memorial HealthCare, University Campus
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
    • Missouri
      • Saint Louis, Missouri, United States, 63104
        • Saint Louis University
    • Texas
      • Dallas, Texas, United States, 75390-9195
        • University of Texas Southwestern - Dallas
    • Virginia
      • Richmond, Virginia, United States, 23298-0341
        • Medical College of Virginia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Peg-interferon alfa-2a 90 mcg/week
Drug: Peginterferon alfa-2a + Ribavirin
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
Other Names:
  • Pegasys (Hoffman-La Roche)
  • Copegus (Hoffman-La Roche)
Drug: Peginterferon alfa-2a
90 mcg/week injection, for 3.5 years
Other Names:
  • Pegasys (Hoffman-La Roche)
Active Comparator: 2
Standard of care followup
Drug: Peginterferon alfa-2a + Ribavirin
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
Other Names:
  • Pegasys (Hoffman-La Roche)
  • Copegus (Hoffman-La Roche)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 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
1400 days (3.85 years) post randomization
Increase in Ishak Fibrosis Score by 2 Points or More at 2 or 4 Year Biopsies
Time Frame: 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)
1400 days (3.85 years) post randomization
Death From Any Cause
Time Frame: 1400 days (3.85 years) post randomization
1400 days (3.85 years) post randomization
Development of Hepatocellular Carcinoma (HCC)
Time Frame: 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.
1400 days (3.85 years) post randomization
Child-Turcotte-Pugh (CTP) Score of 7 or Higher at Two Consecutive Study Visits
Time Frame: 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)
1400 days (3.85 years) post randomization
Variceal Hemorrhage
Time Frame: 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
1400 days (3.85 years) post randomization
Ascites
Time Frame: 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.
1400 days (3.85 years) post randomization
Spontaneous Bacterial Peritonitis
Time Frame: 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.
1400 days (3.85 years) post randomization
Hepatic Encephalopathy
Time Frame: 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).
1400 days (3.85 years) post randomization

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborators

National Cancer Institute (NCI)
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute on Minority Health and Health Disparities (NIMHD)
Hoffmann-La Roche

Investigators

  • Principal Investigator: Gregory T. Everson, M.D., UCHSC (University of Colorado)
  • Principal Investigator: Adrian M. Di Bisceglie, M.D., St. Louis University
  • Principal Investigator: William M. Lee, M.D., University of Texas, Southwestern Medical Center at Dallas
  • Principal Investigator: Marc Ghany, M.D., Lds, Niddk, Nih
  • Principal Investigator: Jules L. Dienstag, M.D., Massachusetts General Hospital
  • Principal Investigator: Mitchell Shiffman, M.D., Medical College of Virginia
  • Principal Investigator: Anna Lok, M.D., University of Michigan
  • Principal Investigator: Tim Morgan, M.D., University of California-Irvine/VA Medical Center-Long Beach
  • Principal Investigator: Karen Lindsay, M.D., M.M.M., Usc School Of Medicine
  • Principal Investigator: Gyongyi Szabo, M.D., Ph.D., UMass Medical School

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2000

Primary Completion (Actual)

April 1, 2007

Study Completion (Actual)

October 1, 2009

Study Registration Dates

First Submitted

August 8, 2000

First Submitted That Met QC Criteria

August 8, 2000

First Posted (Estimate)

August 9, 2000

Study Record Updates

Last Update Posted (Actual)

May 12, 2020

Last Update Submitted That Met QC Criteria

April 29, 2020

Last Verified

April 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HALT C
  • N01-DK-9-2328 (Other Grant/Funding Number: NIH NIDDK Contract)
  • N01-DK-9-2323 (Other Grant/Funding Number: NIH NIDDK Contract)
  • N01-DK-9-2324 (Other Grant/Funding Number: NIH NIDDK Contract)
  • N01-DK-9-2325 (Other Grant/Funding Number: NIH NIDDK Contract)
  • N01-DK-9-2326 (Other Grant/Funding Number: NIH NIDDK Contract)
  • N01-DK-9-2321 (Other Grant/Funding Number: NIH NIDDK Contract)
  • N01-DK-9-2327 (Other Grant/Funding Number: NIH NIDDK Contract)
  • N01-DK-9-2319 (Other Grant/Funding Number: NIH NIDDK Contract)
  • N01-DK-9-2318 (Other Grant/Funding Number: NIH NIDDK Contract)
  • N01-DK-9-2320 (Other Grant/Funding Number: NIH NIDDK Contract)
  • N01-DK-9-2322 (Other Grant/Funding Number: NIH NIDDK Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data are available at the NIDDK Central Repository: https://repository.niddk.nih.gov/studies/halt-c/?query=HALT-C

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Fibrosis, Liver

Clinical Trials on Peginterferon alfa-2a + Ribavirin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Azerbaijan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe