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Kidney Week

Abstract: FR-OR085

Randomized Clinical Trial in Older Adult Kidney Transplant Recipients Comparing Everolimus and Reduced-Dose Tacrolimus with Mycophenolate and Tacrolimus Immunosuppression: The OPTIMIZE Study

Session Information

Category: Transplantation

  • 2102 Transplantation: Clinical

Authors

  • Berger, Stefan P., Universitair Medisch Centrum Groningen, Groningen, GR, Netherlands
  • de Boer, Silke, Universitair Medisch Centrum Groningen, Groningen, GR, Netherlands
  • Jonker, Jip, Universitair Medisch Centrum Groningen, Groningen, GR, Netherlands
  • Bemelman, Frederike J., Amsterdam UMC Locatie AMC, Amsterdam, NH, Netherlands
  • Betjes, Michiel G.H., Erasmus MC, Rotterdam, ZH, Netherlands
  • De Vries, Aiko P.J., Universiteit Leiden, Leiden, ZH, Netherlands
  • Hilbrands, Luuk, Radboud Universiteit, Nijmegen, GE, Netherlands
  • Hilhorst, Marc, Amsterdam UMC Locatie AMC, Amsterdam, NH, Netherlands
  • Kuypers, Dirk R., Katholieke Universiteit Leuven Universitaire Ziekenhuizen Leuven Campus Gasthuisberg, Leuven, Flanders, Belgium
  • Vart, Priya, Universitair Medisch Centrum Groningen, Groningen, GR, Netherlands
  • Van Zuilen, Arjan D., Universitair Medisch Centrum Utrecht, Utrecht, UT, Netherlands
  • Hesselink, Dennis Alexander, Erasmus MC, Rotterdam, ZH, Netherlands
  • Sanders, Jan-Stephan, Universitair Medisch Centrum Groningen, Groningen, GR, Netherlands
Background

We hypothesized that older kidney transplant recipients receiving corticosteroids, everolimus (EVR) and reduced-dose tacrolimus have better outcomes than patients receiving corticosteroids, mycophenolate mofetil (MMF) and tacrolimus.

Methods

The OPTIMIZE study was a randomized controlled clinical trial in kidney transplant recipients over 65 years in The Netherlands and Belgium. Patients (65+) receiving a kidney from a deceased donor over 65 years (stratum A), or a kidney from a deceased donor younger than 65 years or a living donor (Stratum B) were included.
At transplantation, patients were randomized to EVR or MMF groups. Tacrolimus target trough levels in the EVR group were 5-7 µg/L until 3 months, 2-4 from 3 to 6 months, and 1.5-4 from 6 months onwards. Tacrolimus target trough levels in the MMF group were 8-12 µg/L, 6-10, and 5-8. Everolimus target trough levels were 3-8 µg/L.
The primary endpoint of successful transplantation was defined as being alive with a functioning graft with an eGFR above a predefined threshold at 2 years after transplantation. Predefined eGFR thresholds were 30 ml/min*1.73m2 (stratum A) or 45 ml/min*1.73m2 (stratum B).

Results

379 patients were randomized of whom 197 in stratum A and 182 in stratum B. The mean trough levels for everolimus and tacrolimus were within the target range throughout the study. There was no statistically significant difference in the frequency of successful transplantation at 2 years between the EVR and MMF groups (EVR 94 (50.3 %), MMF 110 (57.3%); p = 0.17). Regarding the predefined secondary outcomes, patient survival (EVR 167 (89.3%), MMF 171 (89.1%); p = 0.94) and graft survival (EVR 155 (82.9%), MMF 162 (84.4%); p = 0.70) did not differ significantly at 2 years. There was no significant difference in the frequency of treated rejection (EVR 39 (20.6%), MMF 34 (17.4%); p = 0.42). Within strata A and B there were no significant differences in the endpoints.

Conclusion

Everolimus and reduced-dose tacrolimus did not result in a higher rate of successful transplantation in older transplant recipients compared to MMF and tacrolimus immunosuppression.

Funding

  • Commercial Support – Chiesi Pharmaceuticals

Digital Object Identifier (DOI)