Long Term Interferon for Patients Who Did Not Clear Hepatitis C Virus With Standard Treatment - Full Text View

Sponsor:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborators:	National Institute of Allergy and Infectious Diseases (NIAID) National Center on Minority Health and Health Disparities (NCMHD) National Cancer Institute (NCI) Hoffmann-La Roche
Information provided by:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:	NCT00006164

Purpose

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 HCV. 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	Intervention	Phase
Chronic Hepatitis C Cirrhosis, Liver Fibrosis, Liver Hepatic Cirrhosis	Drug: Peginterferon alfa-2a + Ribavirin Drug: Peginterferon alfa-2a	Phase III

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Parallel Assignment, Efficacy Study
Official Title:	Hepatitis C Antiviral Long-term Treatment Against Cirrhosis Trial (HALT-C)

Resource links provided by NLM:

MedlinePlus related topics: Cirrhosis Hepatitis Hepatitis C Liver Diseases

Drug Information available for: Ribavirin Peginterferon Alfa-2a

U.S. FDA Resources

Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Death From Any Cause [ Time Frame: 1400 days (3.85 years) post randomization ] [ Designated as safety issue: Yes ]
Development of Hepatocellular Carcinoma (HCC) [ Time Frame: 1400 days (3.85 years) post randomization ] [ Designated as safety issue: No ]
Child-Turcotte-Pugh (CTP) Score of 7 or Higher at Two Consecutive Study Visits [ Time Frame: 1400 days (3.85 years) post randomization ] [ Designated as safety issue: No ]
Variceal Hemorrhage [ Time Frame: 1400 days (3.85 years) post randomization ] [ Designated as safety issue: No ]
Ascites [ Time Frame: 1400 days (3.85 years) post randomization ] [ Designated as safety issue: No ]
Spontaneous Bacterial Peritonitis [ Time Frame: 1400 days (3.85 years) post randomization ] [ Designated as safety issue: No ]
Hepatic Encephalopathy [ Time Frame: 1400 days (3.85 years) post randomization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Serious Adverse Events [ Time Frame: 1400 days (3.85 years) post randomization ] [ Designated as safety issue: Yes ]
Events Requiring Dose Reductions (in Both Treatment Groups). [ Time Frame: 1400 days (3.85 years) post randomization ] [ Designated as safety issue: Yes ]
Changes in Fibrosis From Baseline at Year 2 or Year 4 Biopsy. [ Time Frame: 1400 days (3.85 years) post randomization ] [ Designated as safety issue: No ]
Presumed Hepatocellular Carcinoma (HCC) [ Time Frame: 1400 days (3.85 years) post randomization ] [ Designated as safety issue: No ]
Quality of Life [ Time Frame: 1400 days (3.85 years) post randomization ] [ Designated as safety issue: No ]

Enrollment:	1050
Study Start Date:	June 2000
Estimated Study Completion Date:	October 2009
Primary Completion Date:	April 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 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 Drug: Peginterferon alfa-2a 90 mcg/week injection, for 3.5 years
2: Active Comparator 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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: 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
St. 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 Center on Minority Health and Health Disparities (NCMHD)

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.	UTSW-Dallas
Principal Investigator:	Marc Ghany, M.D.	LDS, NIDDK, NIH
Principal Investigator:	Jules L. Dienstag, M.D.	Massachusetts General Hospital/ Harvard Medical School
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

More Information

Additional Information:

HALT-C Web Site This link exits the ClinicalTrials.gov site

Publications:

Di Bisceglie AM, Shiffman ML, Everson GT, Lindsay KL, Everhart JE, Wright EC, Lee WM, Lok AS, Bonkovsky HL, Morgan TR, Ghany MG, Morishima C, Snow KK, Dienstag JL; HALT-C Trial Investigators. Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon. N Engl J Med. 2008 Dec 4;359(23):2429-41.

Lee WM, Dienstag JL, Lindsay KL, Lok AS, Bonkovsky HL, Shiffman ML, Everson GT, Di Bisceglie AM, Morgan TR, Ghany MG, Morishima C, Wright EC, Everhart JE; HALT-C Trial Group. Evolution of the HALT-C Trial: pegylated interferon as maintenance therapy for chronic hepatitis C in previous interferon nonresponders. Control Clin Trials. 2004 Oct;25(5):472-92.

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Freedman ND, Everhart JE, Lindsay KL, Ghany MG, Curto TM, Shiffman ML, Lee WM, Lok AS, Di Bisceglie AM, Bonkovsky HL, Hoefs JC, Dienstag JL, Morishima C, Abnet CC, Sinha R; HALT-C Trial Group. Coffee intake is associated with lower rates of liver disease progression in chronic hepatitis C. Hepatology. 2009 Nov;50(5):1360-9.

Everhart JE, Lok AS, Kim HY, Morgan TR, Lindsay KL, Chung RT, Bonkovsky HL, Ghany MG; HALT-C Trial Group. Weight-related effects on disease progression in the hepatitis C antiviral long-term treatment against cirrhosis trial. Gastroenterology. 2009 Aug;137(2):549-57. Epub 2009 May 13.

Lok AS, Everhart JE, Chung RT, Kim HY, Everson GT, Hoefs JC, Greenson JK, Sterling RK, Lindsay KL, Lee WM, Di Bisceglie AM, Bonkovsky HL, Ghany MG, Morishima C; HALT-C Trial Group. Evolution of hepatic steatosis in patients with advanced hepatitis C: results from the hepatitis C antiviral long-term treatment against cirrhosis (HALT-C) trial. Hepatology. 2009 Jun;49(6):1828-37.

Lok AS, Seeff LB, Morgan TR, di Bisceglie AM, Sterling RK, Curto TM, Everson GT, Lindsay KL, Lee WM, Bonkovsky HL, Dienstag JL, Ghany MG, Morishima C, Goodman ZD; HALT-C Trial Group. Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastroenterology. 2009 Jan;136(1):138-48. Epub 2008 Sep 18.

Lindsay KL, Morishima C, Wright EC, Dienstag JL, Shiffman ML, Everson GT, Lok AS, Bonkovsky HL, Lee WM, Morgan TR, Ghany MG; HALT-C Trial. Blunted cytopenias and weight loss: new correlates of virologic null response to re-treatment of chronic hepatitis C. Clin Gastroenterol Hepatol. 2008 Feb;6(2):234-41.

Responsible Party:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) ( James E. Everhart, MD, MPH, Project Officer )
Study ID Numbers:	HALT C, N01-DK-9-2328, N01-DK-9-2328, N01-DK-9-2323, N01-DK-9-2324, N01-DK-2325, N01-DK-9-2326, N01-DK-9-2321, N01-DK-9-2327, N01-DK-9-2319, N01-9-2318, N01-DK-9-2320, N01-DK-9-2322
Study First Received:	August 8, 2000
Results First Received:	June 9, 2009
Last Updated:	September 3, 2009
ClinicalTrials.gov Identifier:	NCT00006164 History of Changes
Health Authority:	United States: Food and Drug Administration

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:

Antimetabolites
Anti-Infective Agents
Liver Diseases
Flaviviridae Infections
Hepatitis, Chronic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Fibrosis
Physiological Effects of Drugs
Ribavirin
Hepatitis, Viral, Human
Liver Cirrhosis
Pathologic Processes
Therapeutic Uses

Growth Inhibitors
Hepatitis C
Angiogenesis Modulating Agents
RNA Virus Infections
Growth Substances
Antiviral Agents
Angiogenesis Inhibitors
Pharmacologic Actions
Virus Diseases
Hepatitis
Digestive System Diseases
Peginterferon alfa-2a
Interferon Alfa-2a
Hepatitis C, Chronic

ClinicalTrials.gov processed this record on November 09, 2009