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Study Results
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Long Term Interferon for Patients Who Did Not Clear Hepatitis C Virus With Standard Treatment (HALT-C)
This study is ongoing, but not recruiting participants.
Study NCT00006164   Information provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First Received: August 8, 2000   Last Updated: September 3, 2009   History of Changes
Study Type: Interventional
Study Design: Randomized, Open Label, Parallel Assignment
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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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

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   [ 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   [ 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   [ 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)   [ 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   [ 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   [ 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   [ 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   [ 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   [ 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   [ 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




  Serious Adverse Events
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  Other Adverse Events
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  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.


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.  


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:
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.

Other Publications:
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.

Publications automatically indexed to this study:
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





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