A 3-month, Multicenter, Randomized, Open-label Study to Evaluate the Impact on Wound Healing of the Early (vs Delayed) Introduction of Everolimus in De Novo Kidney Transplant Recipients, With a Follow-up Evaluation at 12 Months After Transplant (NEVERWOUND Study)

Transplantation. 2020 Feb;104(2):374-386. doi: 10.1097/TP.0000000000002851.

Abstract

Background: The risk of wound healing complications (WHCs) and the early use of mammalian target of rapamycin inhibitors after kidney transplantation (KT) have not been fully addressed.

Methods: The NEVERWOUND study is a 3-month, multicenter, randomized, open-label study designed to evaluate whether a delayed (ie, 28 ± 4 d posttransplant) immunosuppression regimen based on everolimus (EVR) reduces the risk of WHC versus EVR started immediately after KT. Secondary endpoints were treatment failure (biopsy-proven acute rejection, graft loss, or death), delayed graft function, patient and graft survival rates, and renal function.

Results: Overall, 394 KT recipients were randomized to receive immediate (N = 197) or delayed (N = 197) EVR after KT. At 3 months, WHC-free rates in the immediate EVR versus delayed EVR arm, considering the worst- and best-case scenario approach, were 0.68 (95% confidence interval [CI], 0.62-0.75) versus 0.62 (95% CI, 0.55-0.68) (log-rank P = 0.56) and 0.70 (95% CI, 0.64-0.77) versus 0.72 (95% CI, 0.65-0.78) (log-rank P = 0.77), respectively. The 3- and 12-month treatment failure rates, delayed graft function and renal function, and patient and graft survival were not different between the arms.

Conclusions: The early introduction of EVR after KT did not increase the risk of WHC, showing good efficacy and safety profile.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biopsy
  • Everolimus / therapeutic use*
  • Female
  • Follow-Up Studies
  • Graft Rejection / diagnosis
  • Graft Rejection / epidemiology
  • Graft Rejection / prevention & control*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Incidence
  • Italy / epidemiology
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Postoperative Period
  • Prospective Studies
  • Survival Rate / trends
  • Time Factors
  • Transplant Recipients*
  • Wound Healing / drug effects*

Substances

  • Immunosuppressive Agents
  • Everolimus