Evolution of the HALT-C Trial: Pegylated interferon as maintenance therapy for chronic hepatitis C in previous interferon nonresponders

William M. Lee, Jules L. Dienstag, Karen L. Lindsay, Anna S. Lok, Herbert L. Bonkovsky, Mitchell L. Shiffman, Gregory T. Everson, Adrian M. Di Bisceglie, Timothy R. Morgan, Marc G. Ghany, Chihiro Morishima, Elizabeth C. Wright, James E. Everhart

Research output: Contribution to journalArticle

134 Citations (Scopus)

Abstract

The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial was designed to determine whether maintenance interferon therapy could slow disease progression in patients who had failed to eradicate hepatitis C virus (HCV) during prior interferon treatment (nonresponders). Ten clinical sites, a virological testing center, and a data coordinating center (DCC) were selected to collaborate in the design and implementation of the final protocol. Eligible patients had been treated previously with interferon for at least 12 weeks, with or without another antiviral, ribavirin, but still had persistent viremia. Because patients had received a variety of prior treatments, and as a perceived benefit of enrollment, we incorporated a Lead-in period of treatment with long-acting pegylated interferon alfa-2a plus ribavirin into the study design, a combination believed to be more effective but not approved by the Food and Drug Administration at the Trial's inception. If patients failed to achieve clearance of virus from the blood after 20 weeks of this Lead-in therapy, they were entered into the main trial at week 24 and randomized to receive either a lower dose of pegylated interferon weekly alone or no further therapy for an additional 3 1/2 years. The original protocol was amended later in three respects to improve enrollment and to adapt to Food and Drug Administration approval of the Lead-in therapy, including allowing patients to proceed directly to the randomized part of the study if treatment resembling the Lead-in had been completed. The protocol changes enhanced enrollment while upholding the original goals of the study and its integrity.

Original languageEnglish (US)
Pages (from-to)472-492
Number of pages21
JournalControlled Clinical Trials
Volume25
Issue number5
DOIs
StatePublished - Oct 2004

Fingerprint

Chronic Hepatitis C
Hepatitis C
Interferons
Antiviral Agents
Fibrosis
Therapeutics
Ribavirin
United States Food and Drug Administration
Drug Approval
Viremia
Hepacivirus
Disease Progression
Maintenance
Viruses

Keywords

  • Chronic hepatitis C
  • Cirrhosis
  • Controlled trials
  • Interferons
  • Maintenance therapy
  • Viral hepatitis

ASJC Scopus subject areas

  • Pharmacology

Cite this

Evolution of the HALT-C Trial : Pegylated interferon as maintenance therapy for chronic hepatitis C in previous interferon nonresponders. / Lee, William M.; Dienstag, Jules L.; Lindsay, Karen L.; Lok, Anna S.; Bonkovsky, Herbert L.; Shiffman, Mitchell L.; Everson, Gregory T.; Di Bisceglie, Adrian M.; Morgan, Timothy R.; Ghany, Marc G.; Morishima, Chihiro; Wright, Elizabeth C.; Everhart, James E.

In: Controlled Clinical Trials, Vol. 25, No. 5, 10.2004, p. 472-492.

Research output: Contribution to journalArticle

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 2004, 'Evolution of the HALT-C Trial: Pegylated interferon as maintenance therapy for chronic hepatitis C in previous interferon nonresponders', Controlled Clinical Trials, vol. 25, no. 5, pp. 472-492. https://doi.org/10.1016/j.cct.2004.08.003
Lee, William M. ; Dienstag, Jules L. ; Lindsay, Karen L. ; Lok, Anna S. ; Bonkovsky, Herbert L. ; Shiffman, Mitchell L. ; Everson, Gregory T. ; Di Bisceglie, Adrian M. ; Morgan, Timothy R. ; Ghany, Marc G. ; Morishima, Chihiro ; Wright, Elizabeth C. ; Everhart, James E. / Evolution of the HALT-C Trial : Pegylated interferon as maintenance therapy for chronic hepatitis C in previous interferon nonresponders. In: Controlled Clinical Trials. 2004 ; Vol. 25, No. 5. pp. 472-492.
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