A randomized long-term trial of tacrolimus and sirolimus versus tacrolimus and mycophenolate mofetil versus cyclosporine (NEORAL) and sirolimus in renal transplantation. I. Drug interactions and rejection at one year

Ciancio, Gaetano; Burke, George W.; Gaynor, Jeffrey J.; Mattiazzi, Adela; Roth, David; Kupin, Warren; Nicolas, Maud; Ruiz, Phillip; Rosén, Anne; Miller, Joshua

doi:10.1097/01.tp.0000101290.20629.dc

Cited by 118 publications

(104 citation statements)

References 26 publications

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“…Using the intent-to-treat approach, differences in AR rate among the three study groups were noted within the first 36 mo (P ϭ 0.05), but no differences existed in AR rate beyond 36 mo post-transplant (P ϭ 0.95). As reported previously, 15,17 the AR rate during the first 12 mo post-transplant was significantly higher for CSA/SRL in comparison with Groups TAC/SRL and TAC/MMF combined (P ϭ 0.03), whereas the AR rate during months 13 to 36 post-transplant was significantly higher for TAC/SRL in comparison with Groups TAC/ MMF and CSA/SRL combined (P ϭ 0.01). Thus, the AR rate during the first 36 mo post-transplant, 17 and throughout the study, has favored TAC/MMF in comparison with TAC/SRL and CSA/SRL combined (P ϭ 0.02 and 0.03, respectively; Figure 1).…”

Section: Ar Cai and Gfsupporting

confidence: 66%

“…As previously reported, [15][16] between May 2000 and December 2001, 150 recipients between 14 to 78 yr of age, of either deceased donor(DD) or non-HLA identical living donor (LD) first kidney transplants, were randomized immediately before transplantation into one of three study groups (the center institutional review board approved the protocol; patients gave written informed consent before enrollment): TAC/SRL, TAC/MMF, and CSA/SRL. In each arm, the CNI was not started until renal function had improved (serum creatinine concentration (Cr) Ͻ4 mg/dl absent dialysis).…”

Section: Concise Methodsmentioning

confidence: 99%

“…All patients received daclizumab induction, maintenance corticosteroids, and nonimmunosuppressive adjunctive therapy, as previously reported. 8,[15][16][17] A protocol violation was defined as the patient discontinuing one or both of the planned maintenance drugs for at least 1 yr or the addition of a nonplanned maintenance drug. Noncompliance was defined as the recipient consistently failing to take his/her immunosuppressive medications as prescribed.…”

Section: Concise Methodsmentioning

confidence: 99%

“…AR occurred in 15,6, and 14 patients in Groups TAC/ SRL, TAC/MMF, and CSA/SRL, respectively; actuarial estimates ϮSEofthepercentagedevelopingARthrough96mopost-transplant were 34 Ϯ 7%, 14 Ϯ 5%, and 31 Ϯ 7%, respectively ( Figure 1). Using the intent-to-treat approach, differences in AR rate among the three study groups were noted within the first 36 mo (P ϭ 0.05), but no differences existed in AR rate beyond 36 mo post-transplant (P ϭ 0.95).…”

Section: Ar Cai and Gfmentioning

confidence: 99%

“…[15][16][17] In the present report, we compare, at a median follow-up of eight years post-transplant, the efficacy/ safety of TAC in decreasing maintenance dosage combined with SRL versus MMF (TAC/SRL versus TAC/MMF), and CSA in decreasing maintenance dosage combined with SRL (CSA/ SRL) in adult primary-kidney-transplant recipients.…”

mentioning

confidence: 99%

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Randomized Trial of Immunosuppressive Regimens in Renal Transplantation

Guerra

Ciancio

Gaynor

et al. 2011

Journal of the American Society of Nephrology

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The optimal long-term regimen for immunosuppression for kidney transplant recipients is unknown. We conducted a randomized trial involving 150 kidney transplant recipients to compare tacrolimus/sirolimus, tacrolimus/mycophenolate mofetil (MMF), and cyclosporine/sirolimus. All patients received daclizumab induction and maintenance corticosteroids. Median follow-up was 8 yr post-transplant. Acute rejection (AR) occurred significantly less often among those treated with tacrolimus/MMF (12%) than among those treated with tacrolimus/sirolimus (30%) or cyclosporine/sirolimus (28%). Mean estimated GFR was consistently higher in the tacrolimus/MMF arm, especially after controlling for donor age in a multivariable model during the first 36 mo (P Յ 0.008). The rate of dying with a functioning graft was significantly higher among those treated with tacrolimus/sirolimus (26%) than among those treated with tacrolimus/ MMF (12%) or cyclosporine/sirolimus (4%). We did not observe significant differences in actuarial graft survival at 8 yr post-transplant between the groups. Patient noncompliance seemed responsible for 45% (13/29) of observed graft failures, with 11 of these occurring after 36 mo. Significantly more viral infections, protocol violations, and need for antilipid therapy occurred among patients receiving sirolimus, but we did not observe differences between the groups with regard to infections requiring hospitalization or new-onset diabetes. Taken together, these results suggest that maintenance therapy with tacrolimus/MMF is more favorable than either tacrolimus/sirolimus or cyclosporine/sirolimus.

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Section: Ar Cai and Gfsupporting

confidence: 66%

Section: Concise Methodsmentioning

confidence: 99%

Section: Concise Methodsmentioning

confidence: 99%

Section: Ar Cai and Gfmentioning

confidence: 99%

mentioning

confidence: 99%

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Randomized Trial of Immunosuppressive Regimens in Renal Transplantation

Guerra

Ciancio

Gaynor

et al. 2011

Journal of the American Society of Nephrology

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Tacrolimus versus cyclosporin as primary immunosuppression for kidney transplant recipients

Webster

Taylor

Chapman

et al. 2005

Cochrane Database of Systematic Reviews

201

170

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Tacrolimus is superior to cyclosporin in improving graft survival and preventing acute rejection after kidney transplantation, but increases post-transplant diabetes, neurological and gastrointestinal side effects. Treating 100 recipients with tacrolimus instead of cyclosporin would avoid 12 suffering acute rejection, two losing their graft but cause an extra five to become insulin-requiring diabetics.

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Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients

Webster

Lee

Chapman

et al. 2006

Cochrane Database of Systematic Reviews

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TOR-I have been evaluated in four different primary immunosuppressive algorithms; as replacement for CNI and for antimetabolites, in combination with CNI at low and high dose and with variable dose of CNI. Generally, surrogate endpoints for graft survival favour TOR-I (lower risk of acute rejection and higher GFR) and surrogate endpoints for patient outcomes are worsened by TOR-I (bone marrow suppression, lipid disturbance). Long-term hard-endpoint data from methodologically robust RCTs are still needed.

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A randomized long-term trial of tacrolimus and sirolimus versus tacrolimus and mycophenolate mofetil versus cyclosporine (NEORAL) and sirolimus in renal transplantation. I. Drug interactions and rejection at one year

Abstract: This 1-year interim analysis indicates that a decreasing dosage of tacrolimus with either adjunctive sirolimus or MMF may optimize future graft survival versus a less favorable outcome using a similar algorithm with CsA and sirolimus.

Cited by 118 publications

References 26 publications

Randomized Trial of Immunosuppressive Regimens in Renal Transplantation

Randomized Trial of Immunosuppressive Regimens in Renal Transplantation

Tacrolimus versus cyclosporin as primary immunosuppression for kidney transplant recipients

Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients

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