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

This study has been completed.
Sponsor:
Collaborators:
Hoffmann-La Roche
Information provided by:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00006164
First received: August 8, 2000
Last updated: January 12, 2010
Last verified: January 2010
Results First Received: June 9, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Prevention
Conditions: Chronic Hepatitis C
Cirrhosis, Liver
Fibrosis, Liver
Hepatic Cirrhosis
Interventions: Drug: Peginterferon alfa-2a + Ribavirin
Drug: Peginterferon alfa-2a

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Peginterferon Alfa-2a 90 Mcg/Week Treatment with Peginterferon alfa-2a 90 mcg administered once weekly for an additional 42 months
Standard of Care Followup Stop any peginterferon alfa-2a/ribavirin therapy and followed prospectively for an additional 42 months without treatment

Participant Flow:   Overall Study
    Peginterferon Alfa-2a 90 Mcg/Week     Standard of Care Followup  
STARTED     517     533  
COMPLETED     447 [1]   452 [2]
NOT COMPLETED     70     81  
Withdrew or lost to follow-up                 70                 81  
[1] 70 Withdrew or were lost to followup; 158 Discontinued peginterferon but were followed
[2] 81 Withdrew or were lost to followup; 9 took peginterferon outside of protocol



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Peginterferon Alfa-2a 90 Mcg/Week Treatment with Peginterferon alfa-2a 90 mcg administered once weekly for an additional 42 months
Standard of Care Followup Stop any peginterferon alfa-2a/ribavirin therapy and followed prospectively for an additional 42 months without treatment
Total Total of all reporting groups

Baseline Measures
    Peginterferon Alfa-2a 90 Mcg/Week     Standard of Care Followup     Total  
Number of Participants  
[units: participants]
  517     533     1050  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     489     511     1000  
>=65 years     28     22     50  
Age  
[units: years]
Mean ± Standard Deviation
  51.1  ± 7.3     50.1  ± 7.0     50.6  ± 7.2  
Gender  
[units: participants]
     
Female     155     150     305  
Male     362     383     745  
Region of Enrollment  
[units: participants]
     
United States     517     533     1050  



  Outcome Measures
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1.  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   [ Time Frame: 1400 days (3.85 years) post randomization ]

Measure Type Primary
Measure Title 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
Measure Description 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
Time Frame 1400 days (3.85 years) post randomization  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Peginterferon Alfa-2a 90 Mcg/Week Treatment with Peginterferon alfa-2a 90 mcg administered once weekly for an additional 42 months
Standard of Care Followup Stop any peginterferon alfa-2a/ribavirin therapy and followed prospectively for an additional 42 months without treatment

Measured Values
    Peginterferon Alfa-2a 90 Mcg/Week     Standard of Care Followup  
Number of Participants Analyzed  
[units: participants]
  447     452  
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  
[units: participants]
  157     157  

No statistical analysis provided for 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



2.  Primary:   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 ]

Measure Type Primary
Measure Title Increase in Ishak Fibrosis Score by 2 Points or More at 2 or 4 Year Biopsies
Measure Description 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)
Time Frame 1400 days (3.85 years) post randomization  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Peginterferon Alfa-2a 90 Mcg/Week Treatment with Peginterferon alfa-2a 90 mcg administered once weekly for an additional 42 months
Standard of Care Followup Stop any peginterferon alfa-2a/ribavirin therapy and followed prospectively for an additional 42 months without treatment

Measured Values
    Peginterferon Alfa-2a 90 Mcg/Week     Standard of Care Followup  
Number of Participants Analyzed  
[units: participants]
  447     452  
Increase in Ishak Fibrosis Score by 2 Points or More at 2 or 4 Year Biopsies  
[units: participants]
  64     70  

No statistical analysis provided for Increase in Ishak Fibrosis Score by 2 Points or More at 2 or 4 Year Biopsies



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

Measure Type Primary
Measure Title Death From Any Cause
Measure Description No text entered.
Time Frame 1400 days (3.85 years) post randomization  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Peginterferon Alfa-2a 90 Mcg/Week Treatment with Peginterferon alfa-2a 90 mcg administered once weekly for an additional 42 months
Standard of Care Followup Stop any peginterferon alfa-2a/ribavirin therapy and followed prospectively for an additional 42 months without treatment

Measured Values
    Peginterferon Alfa-2a 90 Mcg/Week     Standard of Care Followup  
Number of Participants Analyzed  
[units: participants]
  447     452  
Death From Any Cause  
[units: participants]
  13     8  

No statistical analysis provided for Death From Any Cause



4.  Primary:   Development of Hepatocellular Carcinoma (HCC)   [ Time Frame: 1400 days (3.85 years) post randomization ]

Measure Type Primary
Measure Title Development of Hepatocellular Carcinoma (HCC)
Measure Description

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.
Time Frame 1400 days (3.85 years) post randomization  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Peginterferon Alfa-2a 90 Mcg/Week Treatment with Peginterferon alfa-2a 90 mcg administered once weekly for an additional 42 months
Standard of Care Followup Stop any peginterferon alfa-2a/ribavirin therapy and followed prospectively for an additional 42 months without treatment

Measured Values
    Peginterferon Alfa-2a 90 Mcg/Week     Standard of Care Followup  
Number of Participants Analyzed  
[units: participants]
  447     452  
Development of Hepatocellular Carcinoma (HCC)  
[units: participants]
  12     15  

No statistical analysis provided for Development of Hepatocellular Carcinoma (HCC)



5.  Primary:   Child-Turcotte-Pugh (CTP) Score of 7 or Higher at Two Consecutive Study Visits   [ Time Frame: 1400 days (3.85 years) post randomization ]

Measure Type Primary
Measure Title Child-Turcotte-Pugh (CTP) Score of 7 or Higher at Two Consecutive Study Visits
Measure Description Child-Turcotte-Pugh (CTP) score of 7 or more on two consecutive study visits (score range 5-15, higher score indicates greater hepatic decompensation)
Time Frame 1400 days (3.85 years) post randomization  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Peginterferon Alfa-2a 90 Mcg/Week Treatment with Peginterferon alfa-2a 90 mcg administered once weekly for an additional 42 months
Standard of Care Followup Stop any peginterferon alfa-2a/ribavirin therapy and followed prospectively for an additional 42 months without treatment

Measured Values
    Peginterferon Alfa-2a 90 Mcg/Week     Standard of Care Followup  
Number of Participants Analyzed  
[units: participants]
  447     452  
Child-Turcotte-Pugh (CTP) Score of 7 or Higher at Two Consecutive Study Visits  
[units: participants]
  47     42  

No statistical analysis provided for Child-Turcotte-Pugh (CTP) Score of 7 or Higher at Two Consecutive Study Visits



6.  Primary:   Variceal Hemorrhage   [ Time Frame: 1400 days (3.85 years) post randomization ]

Measure Type Primary
Measure Title Variceal Hemorrhage
Measure Description 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
Time Frame 1400 days (3.85 years) post randomization  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Peginterferon Alfa-2a 90 Mcg/Week Treatment with Peginterferon alfa-2a 90 mcg administered once weekly for an additional 42 months
Standard of Care Followup Stop any peginterferon alfa-2a/ribavirin therapy and followed prospectively for an additional 42 months without treatment

Measured Values
    Peginterferon Alfa-2a 90 Mcg/Week     Standard of Care Followup  
Number of Participants Analyzed  
[units: participants]
  447     452  
Variceal Hemorrhage  
[units: participants]
  3     6  

No statistical analysis provided for Variceal Hemorrhage



7.  Primary:   Ascites   [ Time Frame: 1400 days (3.85 years) post randomization ]

Measure Type Primary
Measure Title Ascites
Measure Description

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.
Time Frame 1400 days (3.85 years) post randomization  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Peginterferon Alfa-2a 90 Mcg/Week Treatment with Peginterferon alfa-2a 90 mcg administered once weekly for an additional 42 months
Standard of Care Followup Stop any peginterferon alfa-2a/ribavirin therapy and followed prospectively for an additional 42 months without treatment

Measured Values
    Peginterferon Alfa-2a 90 Mcg/Week     Standard of Care Followup  
Number of Participants Analyzed  
[units: participants]
  447     452  
Ascites  
[units: participants]
  13     8  

No statistical analysis provided for Ascites



8.  Primary:   Spontaneous Bacterial Peritonitis   [ Time Frame: 1400 days (3.85 years) post randomization ]

Measure Type Primary
Measure Title Spontaneous Bacterial Peritonitis
Measure Description 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.
Time Frame 1400 days (3.85 years) post randomization  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Peginterferon Alfa-2a 90 Mcg/Week Treatment with Peginterferon alfa-2a 90 mcg administered once weekly for an additional 42 months
Standard of Care Followup Stop any peginterferon alfa-2a/ribavirin therapy and followed prospectively for an additional 42 months without treatment

Measured Values
    Peginterferon Alfa-2a 90 Mcg/Week     Standard of Care Followup  
Number of Participants Analyzed  
[units: participants]
  447     452  
Spontaneous Bacterial Peritonitis  
[units: participants]
  0     1  

No statistical analysis provided for Spontaneous Bacterial Peritonitis



9.  Primary:   Hepatic Encephalopathy   [ Time Frame: 1400 days (3.85 years) post randomization ]

Measure Type Primary
Measure Title Hepatic Encephalopathy
Measure Description 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).
Time Frame 1400 days (3.85 years) post randomization  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Peginterferon Alfa-2a 90 Mcg/Week Treatment with Peginterferon alfa-2a 90 mcg administered once weekly for an additional 42 months
Standard of Care Followup Stop any peginterferon alfa-2a/ribavirin therapy and followed prospectively for an additional 42 months without treatment

Measured Values
    Peginterferon Alfa-2a 90 Mcg/Week     Standard of Care Followup  
Number of Participants Analyzed  
[units: participants]
  447     452  
Hepatic Encephalopathy  
[units: participants]
  5     7  

No statistical analysis provided for Hepatic Encephalopathy



10.  Secondary:   Serious Adverse Events   [ Time Frame: 1400 days (3.85 years) post randomization ]

Measure Type Secondary
Measure Title Serious Adverse Events
Measure Description

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.

Time Frame 1400 days (3.85 years) post randomization  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Peginterferon Alfa-2a 90 Mcg/Week Treatment with Peginterferon alfa-2a 90 mcg administered once weekly for an additional 42 months
Standard of Care Followup Stop any peginterferon alfa-2a/ribavirin therapy and followed prospectively for an additional 42 months without treatment

Measured Values
    Peginterferon Alfa-2a 90 Mcg/Week     Standard of Care Followup  
Number of Participants Analyzed  
[units: participants]
  447     452  
Serious Adverse Events  
[units: participants]
  175     155  

No statistical analysis provided for Serious Adverse Events



11.  Secondary:   Events Requiring Dose Reductions (in Both Treatment Groups).   [ Time Frame: 1400 days (3.85 years) post randomization ]
Results not yet posted.   Anticipated Posting Date:   10/2010   Safety Issue:   Yes

12.  Secondary:   Changes in Fibrosis From Baseline at Year 2 or Year 4 Biopsy.   [ Time Frame: 1400 days (3.85 years) post randomization ]
Results not yet posted.   Anticipated Posting Date:   10/2010   Safety Issue:   No

13.  Secondary:   Presumed Hepatocellular Carcinoma (HCC)   [ Time Frame: 1400 days (3.85 years) post randomization ]
Results not yet posted.   Anticipated Posting Date:   10/2010   Safety Issue:   No

14.  Secondary:   Quality of Life   [ Time Frame: 1400 days (3.85 years) post randomization ]
Results not yet posted.   Anticipated Posting Date:   10/2010   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: James E. Everhart, MD, MPH, Project Officer
Organization: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
phone: 301-594-8878
e-mail: EverhartJ@extra.niddk.nih.gov


Publications of Results:
Other Publications:
Publications automatically indexed to this study:


Responsible Party: James E. Everhart, MD, MPH, Project Officer, 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, N01-DK-9-2323, N01-DK-9-2324, N01-DK-9-2325, N01-DK-9-2326, N01-DK-9-2321, N01-DK-9-2327, N01-DK-9-2319, N01-DK-9-2318, N01-DK-9-2320, N01-DK-9-2322
Study First Received: August 8, 2000
Results First Received: June 9, 2009
Last Updated: January 12, 2010
Health Authority: United States: Food and Drug Administration