Randomized controlled trial of sirolimus conversion in cardiac transplant recipients with renal insufficiency

A. Zuckermann, Anne Keogh, M. G. Crespo-Leiro, D. Mancini, F. González Vilchez, L. Almenar, S. Brozena, Howard Eisen, S. See Tai, S. Kushwaha

Research output: Contribution to journalArticle

42 Citations (Scopus)

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/1.73m2 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. This randomized, comparative, multinational study of cardiac transplant recipients with mild to moderate renal insufficiency shows that conversion to sirolimus from calcineurin inhibitor therapy significantly improves renal function but with an attendant risk of acute rejection.

Original languageEnglish (US)
Pages (from-to)2487-2497
Number of pages11
JournalAmerican Journal of Transplantation
Volume12
Issue number9
DOIs
StatePublished - Sep 1 2012

Fingerprint

Sirolimus
Renal Insufficiency
Randomized Controlled Trials
Kidney
Therapeutics
Transplant Recipients
Exanthema
Calcineurin Inhibitors
Diarrhea
Creatinine
Transplantation
Hemodynamics
Infection

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

Zuckermann, A., Keogh, A., Crespo-Leiro, M. G., Mancini, D., Vilchez, F. G., Almenar, L., ... Kushwaha, S. (2012). Randomized controlled trial of sirolimus conversion in cardiac transplant recipients with renal insufficiency. American Journal of Transplantation, 12(9), 2487-2497. https://doi.org/10.1111/j.1600-6143.2012.04131.x
Zuckermann, A. ; Keogh, Anne ; Crespo-Leiro, M. G. ; Mancini, D. ; Vilchez, F. González ; Almenar, L. ; Brozena, S. ; Eisen, Howard ; Tai, S. See ; Kushwaha, S. / Randomized controlled trial of sirolimus conversion in cardiac transplant recipients with renal insufficiency. In: American Journal of Transplantation. 2012 ; Vol. 12, No. 9. pp. 2487-2497.
@article{598686a8eba04fc2ae893fdf67d701c4,
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/1.73m2 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. This randomized, comparative, multinational study of cardiac transplant recipients with mild to moderate renal insufficiency shows that conversion to sirolimus from calcineurin inhibitor therapy significantly improves renal function but with an attendant risk of acute rejection.",
author = "A. Zuckermann and Anne Keogh and Crespo-Leiro, {M. G.} and D. Mancini and Vilchez, {F. Gonz{\'a}lez} and L. Almenar and S. Brozena and Howard Eisen and Tai, {S. See} and S. Kushwaha",
year = "2012",
month = "9",
day = "1",
doi = "10.1111/j.1600-6143.2012.04131.x",
language = "English (US)",
volume = "12",
pages = "2487--2497",
journal = "American Journal of Transplantation",
issn = "1600-6135",
publisher = "Wiley-Blackwell",
number = "9",

}

Zuckermann, A, Keogh, A, Crespo-Leiro, MG, Mancini, D, Vilchez, FG, Almenar, L, Brozena, S, Eisen, H, Tai, SS & Kushwaha, S 2012, 'Randomized controlled trial of sirolimus conversion in cardiac transplant recipients with renal insufficiency', American Journal of Transplantation, vol. 12, no. 9, pp. 2487-2497. https://doi.org/10.1111/j.1600-6143.2012.04131.x

Randomized controlled trial of sirolimus conversion in cardiac transplant recipients with renal insufficiency. / Zuckermann, A.; Keogh, Anne; Crespo-Leiro, M. G.; Mancini, D.; Vilchez, F. González; Almenar, L.; Brozena, S.; Eisen, Howard; Tai, S. See; Kushwaha, S.

In: American Journal of Transplantation, Vol. 12, No. 9, 01.09.2012, p. 2487-2497.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Randomized controlled trial of sirolimus conversion in cardiac transplant recipients with renal insufficiency

AU - Zuckermann, A.

AU - Keogh, Anne

AU - Crespo-Leiro, M. G.

AU - Mancini, D.

AU - Vilchez, F. González

AU - Almenar, L.

AU - Brozena, S.

AU - Eisen, Howard

AU - Tai, S. See

AU - Kushwaha, S.

PY - 2012/9/1

Y1 - 2012/9/1

N2 - 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/1.73m2 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. This randomized, comparative, multinational study of cardiac transplant recipients with mild to moderate renal insufficiency shows that conversion to sirolimus from calcineurin inhibitor therapy significantly improves renal function but with an attendant risk of acute rejection.

AB - 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/1.73m2 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. This randomized, comparative, multinational study of cardiac transplant recipients with mild to moderate renal insufficiency shows that conversion to sirolimus from calcineurin inhibitor therapy significantly improves renal function but with an attendant risk of acute rejection.

UR - http://www.scopus.com/inward/record.url?scp=84865582428&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865582428&partnerID=8YFLogxK

U2 - 10.1111/j.1600-6143.2012.04131.x

DO - 10.1111/j.1600-6143.2012.04131.x

M3 - Article

C2 - 22776430

AN - SCOPUS:84865582428

VL - 12

SP - 2487

EP - 2497

JO - American Journal of Transplantation

JF - American Journal of Transplantation

SN - 1600-6135

IS - 9

ER -