June 15, 2004
Early Data Shows Steroid-Free Protocol May Be Safe with Low Rejection Rates
CTI Clinical Trial and Consulting Services announced that Goran Klintmalm, M.D., Ph.D., chief of Baylor Regional Transplant Institute and principle investigator of a study comparing 3 immunosuppressant treatment regimens in liver transplant recipients with hepatitis C, presented preliminary data from the trial at the American Transplant Congress meeting last month in Boston and the International Liver Transplantation Society meeting last week in Kyoto, Japan. A total of 312 patients enrolled in this prospective, multicenter, randomized study at 18 leading U.S. transplant programs. Enrollment began in August 2002 and concluded in March 2004. All patients will be followed for 2 years. Hepatitis C is present in approximately 4 million Americans, and affects 50% of all patients receiving liver transplants. Hepatitis C frequently recurs following liver transplantation, leading to death or retransplantation.
Corticosteroids have been the cornerstone of immunosuppression in transplantation since the 1960s; however, there is much controversy that corticosteroids may in fact increase recurrence of hepatitis C. In addition, the role and effect of mycophenolate mofetil, an immunosuppressant (non-steroid), in hepatitis C liver transplant patients is unclear.
"The purpose of this study is to determine the effect that the withdrawal of steroids, as an immunosuppressant, has on the recurrence of hepatitis C, as well as whether mycophenolate mofetil can reduce and slow down the development of hepatitis C as it recurs in the transplanted liver," said Dr. Klintmalm. "While definitive analysis and conclusions will have to await completion of the trial in approximately 2 years, the early results are very encouraging." Patients were randomized to one of the three treatment regimens at the time of transplantation and will be maintained on this regimen for two years. Treatment regimen 1 includes conventional therapy (tacrolimus) and corticosteroids, but no mycophenolate mofetil; treatment regimen 2 includes tacrolimus, corticosteroids and mycophenolate mofetil; and treatment regimen 3 includes tacrolimus, mycophenolate mofetil and daclizumab (an antibody given to prevent early acute rejection), but no steroids. Liver biopsies will be performed at various times throughout the study to assess treatment failure. Data presented by Dr. Klintmalm on 261 patients enrolled through Dec. 31, 2003, focused on day 90 post transplant data.
The early data from this trial showed that the steroid-free protocol may be safe with low rejection rates. This preliminary analysis demonstrated that all three regimens had similar excellent early patient survival rates ranging between 95-100%, and graft survival rates ranging between 95-97%. In addition, protocol-defined acute rejection rates and hepatitis C recurrence rates were low in all three regimens. The complete avoidance of corticosteroids in regimen 3 had no negative impact on acute rejection incidence or recurrent hepatitis C. However, there appeared to be a decrease in diabetes and hypertension in this group of patients. Further, the use of mycophenolate mofetil in regimens 2 and 3 did not increase hepatitis C recurrence or severity at 90 days post transplant. Finally, in regimen 3, daclizumab appeared to be safe and did not increase early hepatitis C recurrence or severity.
"The data obtained from this study will provide important information to improve the management of hepatitis C patients after liver transplantation," Dr. Klintmalm said. Baylor University Medical Center at Dallas initiated this trial and recruited the other 17 participating study sites. CTI, Clinical Trial and Consulting Services, is managing the trial on behalf of Baylor. Other participating members of the study include Emory University School of Medicine, Lahey Clinic, Mayo Clinic in Rochester, Mayo Clinic in Scottsdale, Medical University of South Carolina, New York Presbyterian Hospital, New York University School of Medicine, Northwestern University Feinberg School of Medicine, Oregon Health and Science University, University of Alabama at Birmingham School of Medicine, University of California - San Francisco Medical Center, University of Chicago Medical Center, University of Cincinnati Medical Center, University of Medicine and Dentistry in New Jersey, University of Southern California Keck School of Medicine, University of Texas Health Science Center at San Antonio, and University of Virginia Medical Center.
"It was particularly gratifying to work with this group of committed liver transplant programs on this study. Enrollment was completed early and participating investigators have been diligent about obtaining all protocol specified procedures," stated Lynn Fallon, senior vice president, CTI. For more information about this research, visit www.BaylorHealth.com.