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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00006164

Acronym

HALT-C

Enrollment

1050

Registered

2000-08-09

Start date

2000-06-30

Completion date

2009-10-31

Last updated

2020-05-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Hepatitis c, Cirrhosis, Liver, Fibrosis, Liver, Hepatic Cirrhosis

Keywords

liver disease, hepatitis c virus, antiviral agent, cirrhosis

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.

Interventions

DRUGPeginterferon 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

DRUGPeginterferon alfa-2a

90 mcg/week injection, for 3.5 years

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Hepatic Encephalopathy	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).
Death From Any Cause	1400 days (3.85 years) post randomization	—
Development of Hepatocellular Carcinoma (HCC)	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	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	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	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	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.
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	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	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)

Secondary

Measure	Time frame	Description
Changes in Fibrosis From Baseline at Year 2 or Year 4 Biopsy.	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)	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	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	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	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.
Serious Adverse Events	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Peginterferon Alfa-2a 90 mcg/Week Treatment with Peginterferon alfa-2a 90 mcg administered once weekly for an additional 42 months	517
Standard of Care Followup Stop any peginterferon alfa-2a/ribavirin therapy and followed prospectively for an additional 42 months without treatment	533
Total	1,050

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Withdrew or lost to follow-up	70	81

Baseline characteristics

Characteristic	Standard of Care Followup	Peginterferon Alfa-2a 90 mcg/Week	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	22 Participants	28 Participants	50 Participants
Age, Categorical Between 18 and 65 years	511 Participants	489 Participants	1000 Participants
Age, Continuous	50.1 years STANDARD_DEVIATION 7	51.1 years STANDARD_DEVIATION 7.3	50.6 years STANDARD_DEVIATION 7.2
Region of Enrollment United States	533 participants	517 participants	1050 participants
Sex: Female, Male Female	150 Participants	155 Participants	305 Participants
Sex: Female, Male Male	383 Participants	362 Participants	745 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	486 / 517	492 / 533
serious Total, serious adverse events	175 / 517	155 / 533

Outcome results

Primary

Ascites

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.