一项为期 3 个月、多中心、随机、开放标签研究，旨在评估早期（与延迟）引入依维莫司对新诊断肾移植受者伤口愈合的影响，在移植后 12 个月进行随访评估（NEVERWOUND 研究）。

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).

机构信息

Fondazione Policlinico Tor Vergata, Dipartimento Scienze Chirurgiche, Università degli Studi di Roma Tor Vergata, Roma, Italy.

AOU Senese, Siena, Italy.

出版信息

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

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.

背景

肾移植（KT）后伤口愈合并发症（WHC）的风险和哺乳动物雷帕霉素靶蛋白抑制剂的早期使用尚未得到充分解决。

方法

NEVERWOUND 研究是一项为期 3 个月、多中心、随机、开放标签研究，旨在评估基于依维莫司（EVR）的延迟（即移植后 28±4d）免疫抑制方案是否降低 WHC 的风险与 KT 后立即开始的 EVR 相比。次要终点是治疗失败（活检证实的急性排斥反应、移植物丢失或死亡）、延迟移植物功能、患者和移植物存活率以及肾功能。

结果

共有 394 名 KT 受者随机分为立即（N=197）或延迟（N=197）接受 EVR。在 3 个月时，考虑最差和最佳情况方法，EVR 即时与延迟 EVR 组的 WHC 无发生率分别为 0.68（95%置信区间[CI]，0.62-0.75）与 0.62（95%CI，0.55-0.68）（对数秩 P=0.56）和 0.70（95%CI，0.64-0.77）与 0.72（95%CI，0.65-0.78）（对数秩 P=0.77）。两组之间 3 个月和 12 个月的治疗失败率、延迟移植物功能和肾功能以及患者和移植物存活率没有差异。