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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)

Tracking Information
First Submitted Date  ICMJE August 8, 2000
First Posted Date  ICMJE August 9, 2000
Results First Submitted Date June 9, 2009
Results First Posted Date September 4, 2009
Last Update Posted Date May 11, 2018
Study Start Date  ICMJE June 2000
Actual Primary Completion Date April 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 11, 2018)
  • 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
  • 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)
  • Death From Any Cause [ Time Frame: 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.
  • 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)
  • 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
  • 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.
  • 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.
  • 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).
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00006164 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 11, 2018)
  • 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.
  • 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)
  • 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
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Long Term Interferon for Patients Who Did Not Clear Hepatitis C Virus With Standard Treatment
Official Title  ICMJE Hepatitis C Antiviral Long-term Treatment Against Cirrhosis Trial (HALT-C)
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 Provided
Study Type  ICMJE Interventional
Study Phase Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Chronic Hepatitis c
  • Cirrhosis, Liver
  • Fibrosis, Liver
  • Hepatic Cirrhosis
Intervention  ICMJE
  • 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)
Study Arms
  • Experimental: 1
    Peg-interferon alfa-2a 90 mcg/week
    Interventions:
    • Drug: Peginterferon alfa-2a + Ribavirin
    • Drug: Peginterferon alfa-2a
  • Active Comparator: 2
    Standard of care followup
    Intervention: Drug: Peginterferon alfa-2a + Ribavirin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 3, 2008)
1050
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date October 2009
Actual Primary Completion Date April 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00006164
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study Sponsor  ICMJE National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborators  ICMJE
  • 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  ICMJE
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
PRS Account National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP