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Comparison of sirolimus plus tacrolimus versus sirolimus plus cyclosporine in high-risk renal allograft recipients: results from an open-label, randomized trial.
Transplantation 2008; 86(9):1187-95T

Abstract

BACKGROUND

The efficacy and safety of sirolimus (SRL) plus tacrolimus (TAC) versus SRL plus cyclosporine (CsA) were compared in high-risk renal allograft recipients.

METHODS

Evaluable patients (448) were randomly assigned (1:1) before transplant to receive SRL+TAC or SRL+CsA with corticosteroids. Eligible patients were black and/or repeat transplant recipients, and/or those with high titer of panel-reactive antibodies.

RESULTS

Demographics were similar between groups. Both treatments demonstrated equivalent efficacy of the composite endpoint at 12 months with efficacy failure rates of 21.9% vs. 23.2% (SRL+TAC vs. SRL+CsA, respectively, 95% CI -10.0 to 7.1, P=0.737). Biopsy-confirmed acute rejection rate (13.8% vs. 17.4%) and graft survival rate (89.7% vs. 90.2%) were similar (SRL+TAC vs. SRL+CsA, respectively). In evaluable patients (received at least 1 dose of study drug), renal function (calculated Nankivell glomerular filtration rate) was not superior in SRL+TAC versus SRL+CsA (54.5 vs. 52.6 mL/min, P=0.466); however, in on-therapy patients, glomerular filtration rate was significantly higher in SRL+TAC at most time points. At 12 months, there were no significant differences in rates of death, discontinuation because of adverse events, hypercholesterolemia, hyperlipemia, or proteinuria. Diarrhea and herpes simplex infections occurred significantly more often in SRL+TAC patients. Hypertension, cardiomegaly, increased creatinine, overdose (primarily calcineurin inhibitor toxicity), acne, urinary tract disorders, lymphocele, and ovarian cysts occurred significantly more often in SRL+CsA patients.

CONCLUSIONS

This study demonstrated that SRL-based therapy was efficacious in high-risk renal allograft recipients in the first year after transplant, providing equivalent efficacy with CsA or TAC, similar graft survival, low biopsy-confirmed acute rejection rates, excellent renal function, and an acceptable safety profile.

Authors+Show Affiliations

Methodist University Hospital, Memphis, TN, USA. aogaber@tmhs.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19005398

Citation

Gaber, A Osama, et al. "Comparison of Sirolimus Plus Tacrolimus Versus Sirolimus Plus Cyclosporine in High-risk Renal Allograft Recipients: Results From an Open-label, Randomized Trial." Transplantation, vol. 86, no. 9, 2008, pp. 1187-95.
Gaber AO, Kahan BD, Van Buren C, et al. Comparison of sirolimus plus tacrolimus versus sirolimus plus cyclosporine in high-risk renal allograft recipients: results from an open-label, randomized trial. Transplantation. 2008;86(9):1187-95.
Gaber, A. O., Kahan, B. D., Van Buren, C., Schulman, S. L., Scarola, J., & Neylan, J. F. (2008). Comparison of sirolimus plus tacrolimus versus sirolimus plus cyclosporine in high-risk renal allograft recipients: results from an open-label, randomized trial. Transplantation, 86(9), pp. 1187-95. doi:10.1097/TP.0b013e318187bab0.
Gaber AO, et al. Comparison of Sirolimus Plus Tacrolimus Versus Sirolimus Plus Cyclosporine in High-risk Renal Allograft Recipients: Results From an Open-label, Randomized Trial. Transplantation. 2008 Nov 15;86(9):1187-95. PubMed PMID: 19005398.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparison of sirolimus plus tacrolimus versus sirolimus plus cyclosporine in high-risk renal allograft recipients: results from an open-label, randomized trial. AU - Gaber,A Osama, AU - Kahan,Barry D, AU - Van Buren,Charles, AU - Schulman,Seth L, AU - Scarola,Joseph, AU - Neylan,John F, AU - ,, PY - 2008/11/14/pubmed PY - 2008/12/17/medline PY - 2008/11/14/entrez SP - 1187 EP - 95 JF - Transplantation JO - Transplantation VL - 86 IS - 9 N2 - BACKGROUND: The efficacy and safety of sirolimus (SRL) plus tacrolimus (TAC) versus SRL plus cyclosporine (CsA) were compared in high-risk renal allograft recipients. METHODS: Evaluable patients (448) were randomly assigned (1:1) before transplant to receive SRL+TAC or SRL+CsA with corticosteroids. Eligible patients were black and/or repeat transplant recipients, and/or those with high titer of panel-reactive antibodies. RESULTS: Demographics were similar between groups. Both treatments demonstrated equivalent efficacy of the composite endpoint at 12 months with efficacy failure rates of 21.9% vs. 23.2% (SRL+TAC vs. SRL+CsA, respectively, 95% CI -10.0 to 7.1, P=0.737). Biopsy-confirmed acute rejection rate (13.8% vs. 17.4%) and graft survival rate (89.7% vs. 90.2%) were similar (SRL+TAC vs. SRL+CsA, respectively). In evaluable patients (received at least 1 dose of study drug), renal function (calculated Nankivell glomerular filtration rate) was not superior in SRL+TAC versus SRL+CsA (54.5 vs. 52.6 mL/min, P=0.466); however, in on-therapy patients, glomerular filtration rate was significantly higher in SRL+TAC at most time points. At 12 months, there were no significant differences in rates of death, discontinuation because of adverse events, hypercholesterolemia, hyperlipemia, or proteinuria. Diarrhea and herpes simplex infections occurred significantly more often in SRL+TAC patients. Hypertension, cardiomegaly, increased creatinine, overdose (primarily calcineurin inhibitor toxicity), acne, urinary tract disorders, lymphocele, and ovarian cysts occurred significantly more often in SRL+CsA patients. CONCLUSIONS: This study demonstrated that SRL-based therapy was efficacious in high-risk renal allograft recipients in the first year after transplant, providing equivalent efficacy with CsA or TAC, similar graft survival, low biopsy-confirmed acute rejection rates, excellent renal function, and an acceptable safety profile. SN - 1534-6080 UR - https://www.unboundmedicine.com/medline/citation/19005398/Comparison_of_sirolimus_plus_tacrolimus_versus_sirolimus_plus_cyclosporine_in_high_risk_renal_allograft_recipients:_results_from_an_open_label_randomized_trial_ L2 - http://dx.doi.org/10.1097/TP.0b013e318187bab0 DB - PRIME DP - Unbound Medicine ER -