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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00006164
Recruitment Status : Completed
First Posted : August 9, 2000
Results First Posted : September 4, 2009
Last Update Posted : May 11, 2018
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute on Minority Health and Health Disparities (NIMHD)
National Cancer Institute (NCI)
Hoffmann-La Roche
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Chronic Hepatitis c Cirrhosis, Liver Fibrosis, Liver Hepatic Cirrhosis Drug: Peginterferon alfa-2a + Ribavirin Drug: Peginterferon alfa-2a Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1050 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Hepatitis C Antiviral Long-term Treatment Against Cirrhosis Trial (HALT-C)
Study Start Date : June 2000
Actual Primary Completion Date : April 2007
Actual Study Completion Date : October 2009


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 Name: 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)



Primary Outcome Measures :
  1. 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

  2. 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)

  3. Death From Any Cause [ Time Frame: 1400 days (3.85 years) post randomization ]
  4. 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.

  5. 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)

  6. 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

  7. 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.

  8. 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.

  9. 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).


Secondary Outcome Measures :
  1. 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.


  2. 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)

  3. 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

  4. 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.

  5. 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.

  6. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00006164


Locations
United States, California
University of California-Irvine/VA Medical Center-Long Beach
Long Beach, California, United States, 90822
USC School of Medicine
Los Angeles, California, United States, 90033
United States, Colorado
UCHSC (University of Colorado)
Denver, Colorado, United States, 80262
United States, Connecticut
University of Connecticut Health Center
Farmington, Connecticut, United States, 06030
United States, Maryland
Lds, Niddk, Nih
Bethesda, Maryland, United States, 20892-1800
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
UMass Memorial HealthCare, University Campus
Worcester, Massachusetts, United States, 01655
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Saint Louis University
Saint Louis, Missouri, United States, 63104
United States, Texas
University of Texas Southwestern - Dallas
Dallas, Texas, United States, 75390-9195
United States, Virginia
Medical College of Virginia
Richmond, Virginia, United States, 23298-0341
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute on Minority Health and Health Disparities (NIMHD)
National Cancer Institute (NCI)
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 of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT00006164     History of Changes
Obsolete Identifiers: NCT00006139
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 )
First Posted: August 9, 2000    Key Record Dates
Results First Posted: September 4, 2009
Last Update Posted: May 11, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
liver disease
hepatitis c virus
antiviral agent
cirrhosis

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Chronic
Fibrosis
Liver Cirrhosis
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Pathologic Processes
Interferons
Ribavirin
Peginterferon alfa-2a
Interferon-alpha
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs