title: Randomized controlled trial of sirolimus conversion in cardiac transplant recipients with renal insufficiency.
abstract: This randomized, comparative, multinational phase 3b/4 study of patients 1-8 years postcardiac transplantation (mean 3.9 years) evaluated the effect of conversion from a calcineurin inhibitor (CNI) to sirolimus on renal function in patients with renal insufficiency. In total, 116 patients on CNI therapy with GFR 40-90 mL/min/1.73 m(2) were randomized (1:1) to sirolimus (n = 57) or CNI (n = 59). Intent-to-treat analysis showed the 1-year adjusted mean change from baseline in creatinine clearance (Cockcroft-Gault) was significantly higher with sirolimus versus CNI treatment (+3.0 vs. -1.4 mL/min/1.73 m(2) , respectively; p = 0.004). By on-therapy analysis, values were +4.7 and -2.1, respectively (p < 0.001). Acute rejection (AR) rates were numerically higher in the sirolimus group; 1 AR with hemodynamic compromise occurred in each group. A significantly higher treatment discontinuation rate due to adverse events (AEs; 33.3% vs. 0%; p < 0.001) occurred in the sirolimus group. Most common treatment-emergent AEs significantly higher in the sirolimus group were diarrhea (28.1%), rash (28.1%) and infection (47.4%). Conversion to sirolimus from CNI therapy improved renal function in cardiac transplant recipients with renal impairment, but was associated with an attendant AR risk and higher discontinuation rate attributable to AEs.
authors: AKH Wien, Vienna, Austria. andreas.zuckermann@meduniwien.ac.at
authors: A
authors: A
authors: Zuckermann
authors: Anne
authors: A
authors: Keogh
authors: M G
authors: MG
authors: Crespo-Leiro
authors: D
authors: D
authors: Mancini
authors: F González
authors: FG
authors: Vilchez
authors: L
authors: L
authors: Almenar
authors: S
authors: S
authors: Brozena
authors: H
authors: H
authors: Eisen
authors: S See
authors: SS
authors: Tai
authors: S
authors: S
authors: Kushwaha
mesh_terms: D000368:Aged; D005260:Female; D005919:Glomerular Filtration Rate; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000503:physiopathology*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus