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 month after transplant (NEVERWOUND study)

BACKGROUND: The risk of Wound Healing Complications (WHC) and the early use of mTORi 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 (i.e. 28 ± 4 days post-transplant) immunosuppression regimen based on everolimus (EVR) reduces the risk of WHC vs EVR started immediately after KT. Secondary endpoints were: treatment failure (biopsy-proven acute rejection, graft loss or death); Delayed Graft Function (DGF); patient and graft survival rates; renal function. RESULTS: Overall, 394 KT recipients were randomized to receive immediate (N=197, IE) or delayed (N=197; DE) EVR after KT. At 3 months, WHC-free rates in the IE vs DE arm, considering the worst- and best-case scenario approach, were 0.68 (95% CI 0.62-0.75) vs 0.62 (95% CI 0.55-0.68)(log-rank p=0.56) and 0.70 (95% CI 0.64-0.77) vs 0.72 (95% CI 0.65-0.78 (log-rank=0.77), respectively. The 3- and 12-month treatment failure rates, DGF and renal function, as well as patient and graft survival, were not different between the arms. CONCLUSION: The early introduction of EVR after KT did not increase the risk of WHC, showing good efficacy and safety profile.