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

Chronic Hepatitis c Clinical Trial

— HALT-C  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006164
• Other study ID #: HALT C
• Secondary ID: N01-DK-9-2328N01
• Status: Completed
• Phase: Phase 3
• Start date: June 2000
• Est. completion date: October 2009

Study information

• Verified date: April 2020
• Source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT00006139

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1050
• Est. completion date: October 2009
• Est. primary completion date: April 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Hepatitis c
• Cirrhosis, Liver
• Fibrosis
• Fibrosis, Liver
• Hepatic Cirrhosis
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Liver Cirrhosis

Intervention

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
• Peginterferon alfa-2a
90 mcg/week injection, for 3.5 years

Locations

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

Sponsors (5)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Hoffmann-La Roche, National Cancer Institute (NCI), National Institute of Allergy and Infectious Diseases (NIAID), National Institute on Minority Health and Health Disparities (NIMHD)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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 — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Primary	Increase in Ishak Fibrosis Score by 2 Points or More at 2 or 4 Year Biopsies	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
Primary	Death From Any Cause		1400 days (3.85 years) post randomization
Primary	Development of Hepatocellular Carcinoma (HCC)	A diagnosis of development of hepatocellular carcinoma (HCC) was based on either; Histology showing HCC (from a biopsy, surgery, or autopsy) or; 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
Primary	Child-Turcotte-Pugh (CTP) Score of 7 or Higher at Two Consecutive Study Visits	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
Primary	Variceal Hemorrhage	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
Primary	Ascites	Any abdominal fluid which is: Mild, moderate or marked on ultrasound; or; Progressive on serial physical examinations; or; 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
Primary	Spontaneous Bacterial Peritonitis	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
Primary	Hepatic Encephalopathy	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	Serious Adverse Events	A serious adverse event (SAE) is an untoward medical occurrence that results in any of the following: Death; Is life threatening (risk of death at the time of the event); Requires in-patient hospitalization or prolongation of existing hospitalization; Results in persistent or significant disability/incapacity; Congenital abnormality or birth defect; Trial outcomes (except death) were not considered serious adverse events.	1400 days (3.85 years) post randomization
Secondary	Changes in Fibrosis From Baseline at Year 2 or Year 4 Biopsy.	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
Secondary	Presumed Hepatocellular Carcinoma (HCC)	Presumed HCC was considered when histology was not available and alpha-fetoprotein (AFP) is <1000 ng/ml, if: A new hepatic lesion was shown on ultrasound and 1 additional imaging showed a hepatic lesion with characteristics of HCC.; AFP> upper limit of normal (ULN) and 2 imaging studies showed a hepatic lesion with characteristics of HCC.; A progressively enlarging hepatic lesion starting as a new defect resulting in patient death.; A new hepatic defect with at least 1 characteristic scan and: Increase in size over time or; Increasing AFP rising to a level of >200 ng/ml	1400 days (3.85 years) post randomization
Secondary	SF-36 Vitality Summary Score	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
Secondary	SF-36 Physical Function Summary Score	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
Secondary	SF-36 Mental Health Summary Score	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