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New Study - “Study of Viral Resistance to Antiviral Therapy of Chronic Hepatitis C (Virahep-C)”

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  • claudine intexas
    Recent large, randomized, controlled trials of therapies for chronic hepatitis C have reported sustained eradication of hepatitis C virus (HCV) and remission
    Message 1 of 1 , Sep 25, 2002
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      Recent large, randomized, controlled trials of therapies for chronic
      hepatitis C have reported sustained eradication of hepatitis C virus
      (HCV) and remission in disease in over half of treated patients. In
      separate studies enrolling more than 1,000 patients each, the
      of peginterferon and ribavirin was found to be superior to standard
      interferon and ribavirin and to achieve sustained virological
      rates of 54% (Lancet 2001;358:958-965) and 56% (Gastroenterology
      2001;120:A55). These excellent response rates provide justification
      for treating
      patients with hepatitis C who have histologic and/or clinical
      of progressive disease.

      Unfortunately, therapies that are proven to be safe and effective in
      well-designed, multicenter, randomized trials may not prove to be as
      or as effective when applied in clinical practice. Perhaps the major
      reason for this discrepancy is that the average patient enrolled in a

      clinical trial that satisfies all inclusion and exclusion criteria
      may not
      be representative of the average patient with hepatitis C in
      Several groups of patients with hepatitis C are underrepresented in
      registration trials of new therapies for this disease�some
      intentionally and some by chance. Such understudied groups include
      children; the
      elderly; minority individuals; patients with comorbidities of human
      immunodeficiency virus infection, neuropsychiatric disease, or renal
      disease; persons in institutions or who are incarcerated; patients
      advanced hepatitis C; and patients who have had a solid organ

      Quite striking in many of the initial large, randomized, controlled
      trials of interferon-based therapy of hepatitis C has been the
      underrepresentation of African Americans. In a combined analysis of
      studies of
      standard interferon monotherapy and combination therapy, less than 5%
      patients enrolled were black, despite the fact that African Americans

      have a higher rate of hepatitis C than non-Hispanic white Americans
      probably account for more than 20% of cases of chronic hepatitis C in

      the United States (Gastroenterology 2000;119:1385-1396). Also
      has been a lower response rate to interferon-based therapies among
      African Americans compared with whites. In several studies, the
      response rate among African Americans was one third to one half of
      that in
      whites. In the recent multinational studies of peginterferon and
      ribavirin, blacks represented less than 5% of patients enrolled and
      response rates that were less than the average, even after
      controlling for
      genotype. The numbers of African Americans in these studies, however,

      were not adequate to provide an accurate estimate of response rate.

      For these reasons, the Division of Digestive Diseases and Nutrition
      NIDDK published a request for applications (RFA) to conduct a
      multicenter clinical trial of peginterferon and ribavirin therapy in
      a cohort of
      patients that would include an adequate number of African Americans
      establish an accurate estimation of the response rate in this group
      to initiate basic research studies of the reasons for nonresponse and

      antiviral resistance. The RFA was published in September
      2000; applications were received in December and reviewed by a
      study section in March 2001. In July 2001, eight clinical centers and
      data coordinating center were awarded. In addition, four ancillary
      studies were funded, which were to focus on analyses of the basis for

      antiviral resistance. The participants are shown below:

      Clinical centers TOP

      Beth Israel Deaconess Medical Center, Dr. Nezam Afdhal
      New York-Presbyterian Medical Center, Drs. Robert Brown and Lorna
      University of Michigan, Drs. Hari Conjeevaram and Robert Fontana
      University of North Carolina, Chapel Hill, Drs. Michael Fried and
      University of Maryland, Dr. Charles Howell
      University of Miami, Drs. Lennox Jeffers and Shvawn Baker
      University of California, San Francisco, Dr. Norah Terrault
      University of Illinois, Chicago, Drs. Thelma Wiley and Thomas Layden

      Ancillary studies TOP

      Cedar-Sinai Medical Center, Los Angeles, Dr. Huiying Yang: Host
      Indiana University, Dr. Milton Taylor: Interferon signaling
      St. Louis University, Dr. John Tavis: Virology
      Portland Veterans Aministration Medical Center, Dr. Hugo Rosen:

      Data coordinating center TOP

      University of Pittsburgh, School of Public Health, Dr. Steven Belle
      NIH staff

      Dr. Patricia Robuck, Project Officer
      Dr. David Kleiner, Pathologist

      The protocol and manual of operations for Virahep-C have now been
      completed. A Web site describing the trial will be available at
      http://www.edc.gsph.pitt.edu/virahepc. The study will enroll 400
      patients with chronic hepatitis C of genotype 1 who have never been
      treated with interferon. Of the total, 200 patients will be African
      Americans and 200 will be white Americans. All will receive a course
      of the
      combination of peginterferon alfa-2a and ribavirin and be followed
      rigorously for symptoms, side effects, compliance, serum biochemical
      of liver disease, and HCV-RNA levels. Special blood samples will be
      taken at specified intervals for studies of immune function,
      signaling, and genetic analyses. The study is being conducted under a

      clinical research and development agreement with Hoffmann LaRoche to
      provide the study medications and support for virologic and other
      measurements. The initial patients are scheduled to start enrollment
      in August
      2002 and the full enrollment is expected within 12 months.

      The elucidation of the nature and determinants of a response to
      antiviral therapy and a more clear delineation of the efficacy of
      therapy in all groups of patients with hepatitis C are areas of high
      priority for the National Institutes of Health in the long-term
      initiative on prevention and control of hepatitis C.

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