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Chronic Hepatitis cPhase 3HALT-CNCT00006164

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

A Phase 3 study testing Peginterferon alfa-2a + Ribavirin and Peginterferon alfa-2a in people with Chronic Hepatitis c and Cirrhosis, Liver, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Peginterferon alfa-2a + Ribavirin and Peginterferon alfa-2a
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,050 participants
Where
11 sitesUnited States
Study dates
Jun 2000to Oct 2009
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • No other liver disease.
  • No unstable major medical diseases or conditions.
  • No major complications of cirrhosis.
  • No recent abuse of alcohol or illicit drugs.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Lds, Niddk, Nih

    Bethesda, Maryland, 20892-1800

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • University of Texas Southwestern - Dallas

    Dallas, Texas, 75390-9195

  • UCHSC (University of Colorado)

    Denver, Colorado, 80262

  • University of Connecticut Health Center

    Farmington, Connecticut, 06030

  • University of California-Irvine/VA Medical Center-Long Beach

    Long Beach, California, 90822

  • USC School of Medicine

    Los Angeles, California, 90033

  • Medical College of Virginia

    Richmond, Virginia, 23298-0341

  • Saint Louis University

    St Louis, Missouri, 63104

  • UMass Memorial HealthCare, University Campus

    Worcester, Massachusetts, 01655

Other trials in United States

About this study

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

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.

Read more

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.

Being tested
Peginterferon alfa-2a + Ribavirin, Peginterferon alfa-2a
Keywords
liver disease, hepatitis c virus, antiviral agent, cirrhosis
Medical subject headings
Hepatitis C, Chronic, Liver Cirrhosis, Liver Diseases, Hepatitis C, Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Peginterferon alfa-2a + RibavirinDrug

    Also called Pegasys (Hoffman-La Roche), Copegus (Hoffman-La Roche)

    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-2aDrug

    Also called Pegasys (Hoffman-La Roche)

    90 mcg/week injection, for 3.5 years

Study groups in NCT00006164
Study groupRoleWhat they receive
1ExperimentalPeg-interferon alfa-2a 90 mcg/week
Receives: Drug: Peginterferon alfa-2a + Ribavirin; Drug: Peginterferon alfa-2a
2Active comparatorStandard of care followup
Receives: Drug: Peginterferon alfa-2a + Ribavirin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 1400 days (3.85 years) post randomization

  2. 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)

    Measured: 1400 days (3.85 years) post randomization

  3. Death From Any Cause

    Measured: 1400 days (3.85 years) post randomization

  4. Development of Hepatocellular Carcinoma (HCC)

    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.

    Measured: 1400 days (3.85 years) post randomization

  5. 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)

    Measured: 1400 days (3.85 years) post randomization

  6. 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

    Measured: 1400 days (3.85 years) post randomization

  7. 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.

    Measured: 1400 days (3.85 years) post randomization

  8. 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.

    Measured: 1400 days (3.85 years) post randomization

  9. 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).

    Measured: 1400 days (3.85 years) post randomization

Secondary outcomes (6)

  1. Serious Adverse Events

    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.

    Measured: 1400 days (3.85 years) post randomization

  2. 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)

    Measured: 1400 days (3.85 years) post randomization

  3. Presumed Hepatocellular Carcinoma (HCC)

    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:
    5. Increase in size over time or
    6. Increasing AFP rising to a level of >200 ng/ml

    Measured: 1400 days (3.85 years) post randomization

  4. 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.

    Measured: 0.5, 1.5, 2.5, and 3.5 years after randomization

  5. 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.

    Measured: 0.5, 1.5, 2.5, and 3.5 years after randomization

  6. 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.

    Measured: 0.5, 1.5, 2.5, and 3.5 years after randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Aug 2000 (estimated)
  2. Study startJun 2000
  3. Primary completionApr 2007
  4. Study completionOct 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,050 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00006164
Sponsor's protocol ID
HALT C
Other IDs
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
Acronym
HALT-C
Status last verified
Apr 2020
First submitted
8 Aug 2000
Last updated
12 May 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Data are available at the NIDDK Central Repository: https://repository.niddk.nih.gov/studies/halt-c/?query=HALT-C

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. doi: 10.1016/j.cct.2004.08.003.

    PubMed 15465617

  • 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. doi: 10.1056/NEJMoa0707615.

    PubMed 19052125

  • Imperial JC, McRae MP, Everson GT. When should I repeat the endoscopy in my patient with compensated cirrhosis, whom I just scoped and who had no or small varices? Transl Gastroenterol Hepatol. 2026 Jan 22;11:22. doi: 10.21037/tgh-25-133. eCollection 2026.

    PubMed 41675321

  • Yu L, Paski SC, Dodge J, Bambha K, Biggins SW, Ioannou GN. Effect of dietary branched chain amino acids on liver related mortality: Results from a large cohort of North American patients with advanced HCV infection. PLoS One. 2023 Apr 25;18(4):e0284739. doi: 10.1371/journal.pone.0284739. eCollection 2023.

    PubMed 37098004

  • Donlin MJ, Lomonosova E, Kiss A, Cheng X, Cao F, Curto TM, Di Bisceglie A, Tavis JE. HCV genome-wide genetic analyses in context of disease progression and hepatocellular carcinoma. PLoS One. 2014 Jul 31;9(7):e103748. doi: 10.1371/journal.pone.0103748. eCollection 2014.

    PubMed 25079603

  • Snow KK, Bell MC, Stoddard AM, Curto TM, Wright EC, Dienstag JL. Processes to manage analyses and publications in a phase III multicenter randomized clinical trial. Trials. 2014 May 7;15:159. doi: 10.1186/1745-6215-15-159.

    PubMed 24886378

  • Morishima C, Shiffman ML, Dienstag JL, Lindsay KL, Szabo G, Everson GT, Lok AS, Di Bisceglie AM, Ghany MG, Naishadham D, Morgan TR, Wright EC; HALT-C Trial Group. Reduction in Hepatic Inflammation Is Associated With Less Fibrosis Progression and Fewer Clinical Outcomes in Advanced Hepatitis C. Am J Gastroenterol. 2012 Sep;107(9):1388-98. doi: 10.1038/ajg.2012.137. Epub 2012 Jun 12.

    PubMed 22688849

  • Morishima C, Di Bisceglie AM, Rothman AL, Bonkovsky HL, Lindsay KL, Lee WM, Koziel MJ, Fontana RJ, Kim HY, Wright EC; HALT-C Trial Group. Antigen-specific T lymphocyte proliferation decreases over time in advanced chronic hepatitis C. J Viral Hepat. 2012 Jun;19(6):404-13. doi: 10.1111/j.1365-2893.2011.01562.x. Epub 2011 Dec 16.

    PubMed 22571902

  • Fontana RJ, Litman HJ, Dienstag JL, Bonkovsky HL, Su G, Sterling RK, Lok AS; HALT-C Trial Group. YKL-40 genetic polymorphisms and the risk of liver disease progression in patients with advanced fibrosis due to chronic hepatitis C. Liver Int. 2012 Apr;32(4):665-74. doi: 10.1111/j.1478-3231.2011.02686.x. Epub 2011 Nov 22.

    PubMed 22103814

  • Everson GT, Shiffman ML, Hoefs JC, Morgan TR, Sterling RK, Wagner DA, Lauriski S, Curto TM, Stoddard A, Wright EC; HALT-C Trial Group. Quantitative liver function tests improve the prediction of clinical outcomes in chronic hepatitis C: results from the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis Trial. Hepatology. 2012 Apr;55(4):1019-29. doi: 10.1002/hep.24752. Epub 2012 Mar 1.

    PubMed 22030902

  • Sterling RK, Wright EC, Morgan TR, Seeff LB, Hoefs JC, Di Bisceglie AM, Dienstag JL, Lok AS. Frequency of elevated hepatocellular carcinoma (HCC) biomarkers in patients with advanced hepatitis C. Am J Gastroenterol. 2012 Jan;107(1):64-74. doi: 10.1038/ajg.2011.312. Epub 2011 Sep 20.

    PubMed 21931376

  • O'Bryan JM, Potts JA, Bonkovsky HL, Mathew A, Rothman AL; HALT-C Trial Group. Extended interferon-alpha therapy accelerates telomere length loss in human peripheral blood T lymphocytes. PLoS One. 2011;6(8):e20922. doi: 10.1371/journal.pone.0020922. Epub 2011 Aug 4.

    PubMed 21829595

  • Rakoski MO, Brown MB, Fontana RJ, Bonkovsky HL, Brunt EM, Goodman ZD, Lok AS, Omary MB; HALT-C Trial Group. Mallory-Denk bodies are associated with outcomes and histologic features in patients with chronic hepatitis C. Clin Gastroenterol Hepatol. 2011 Oct;9(10):902-909.e1. doi: 10.1016/j.cgh.2011.07.006. Epub 2011 Jul 23.

    PubMed 21782771

  • O'Brien TR, Everhart JE, Morgan TR, Lok AS, Chung RT, Shao Y, Shiffman ML, Dotrang M, Sninsky JJ, Bonkovsky HL, Pfeiffer RM; HALT-C Trial Group. An IL28B genotype-based clinical prediction model for treatment of chronic hepatitis C. PLoS One. 2011;6(7):e20904. doi: 10.1371/journal.pone.0020904. Epub 2011 Jul 8.

    PubMed 21760886

  • Hoefs JC, Shiffman ML, Goodman ZD, Kleiner DE, Dienstag JL, Stoddard AM; HALT-C Trial Group. Rate of progression of hepatic fibrosis in patients with chronic hepatitis C: results from the HALT-C Trial. Gastroenterology. 2011 Sep;141(3):900-908.e1-2. doi: 10.1053/j.gastro.2011.06.007. Epub 2011 Jun 12.

    PubMed 21699796

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Peginterferon alfa-2a + Ribavirin and Peginterferon alfa-2a in people with Chronic Hepatitis c and Cirrhosis, Liver, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Sep 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00006164, which also lists 36 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2020.

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