An open-label randomized trial of the safety and efficacy of sirolimus vs. azathioprine in living related renal allograft recipients receiving cyclosporine and prednisone combination.

Publisher: Munksgaard Country of Publication: Denmark NLM ID: 8710240 Publication Model: Print Cited Medium: Print ISSN: 0902-0063 (Print) Linking ISSN: 09020063 NLM ISO Abbreviation: Clin Transplant Subsets: MEDLINE

Original Publication: Copenhagen : Munksgaard,

Azathioprine/*therapeutic use ; Cyclosporine/*therapeutic use ; Graft Rejection/*prevention & control ; Immunosuppressive Agents/*therapeutic use ; Kidney Transplantation/*immunology ; Prednisone/*therapeutic use ; Sirolimus/*therapeutic use; Adult ; Azathioprine/administration & dosage ; Azathioprine/adverse effects ; Cyclosporine/administration & dosage ; Cyclosporine/adverse effects ; Drug Therapy, Combination ; Female ; Humans ; Immunosuppressive Agents/administration & dosage ; Immunosuppressive Agents/adverse effects ; Lipids/blood ; Male ; Prednisone/administration & dosage ; Prednisone/adverse effects ; Prospective Studies ; Safety ; Sirolimus/administration & dosage ; Sirolimus/adverse effects

Background: The ability of sirolimus (SRL), in combination with reduced exposure of cyclosporine, was investigated to prevent acute rejection and associated side effects.
Methods: Between June 1999 and February 2000, 70 recipients of primary one-haplotype living-related donor renal allografts were randomized to receive SRL (2 mg/d) or azathioprine (AZA) (2 mg/kg/d) combined with cyclosporine and prednisone. The primary end-point was a composite of first occurrence of biopsy-confirmed acute rejection, graft loss, or death during the first 3 months after transplantation.
Results: From week 4 to month 12, SRL patients received lower cyclosporine (week 4: 364 mg/d vs. 455 mg/d, p = 0.004; month 12: 195 mg/d vs. 255 mg/d, p = 0.038) doses and showed lower cyclosporine concentrations (week 4: 247 ng/mL vs. 309 ng/mL, p = 0.04; month 12: 143 ng/mL vs. 188 ng/mL, p = 0.045). Compared with AZA, SRL patients showed reduced 3-month primary end point (0% vs. 17.1%, p = 0.025), and reduced incidence of biopsy-confirmed acute rejection at 3 months (0% vs. 14.3%, p = 0.01) but not at 12 months (11.4% vs. 14.3%, NS). Mean creatinine at 12 months were not different (1.8 +/- 0.6 vs. 1.6 +/- 0.6, p = 0.23). Hyperlipidemia was the only adverse event more frequent among SRL patients (49% vs. 17%, p = 0.01). There were no differences in infections and no malignancies in both groups.
Conclusions: The combination of 2 mg fixed doses of SRL, reduced cyclosporine exposure and prednisone was associated with a low incidence of acute rejection and did not result in significantly impaired graft function compared with patients receiving AZA, standard doses of cyclosporine and prednisone.

0 (Immunosuppressive Agents)
0 (Lipids)
83HN0GTJ6D (Cyclosporine)
MRK240IY2L (Azathioprine)
VB0R961HZT (Prednisone)
W36ZG6FT64 (Sirolimus)

Date Created: 20040428 Date Completed: 20040520 Latest Revision: 20191108

20221213

10.1111/j.1399-0012.2004.00113.x

15108768