Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2020 Feb;104(2):374-386.
doi: 10.1097/TP.0000000000002851.

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)

Tommaso Maria Manzia  1 , Mario Carmellini  2 , Paola Todeschini  3 , Antonio Secchi  4 , Silvio Sandrini  5 , Enrico Minetti  6 , Lucrezia Furian  7 , Gionata Spagnoletti  8 , Francesco Pisani  9 , Gian Benedetto Piredda  10 , Gianni Cappelli  11 , GIuseppe Tisone  1
Affiliations
Randomized Controlled Trial

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)

Tommaso Maria Manzia et al. Transplantation. 2020 Feb.

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1.
FIGURE 1.
Study design. C0, immunosuppression blood levels, before morning dose; C2, immunosuppression blood levels, 2 h after morning dose; CsA, cyclosporine A; D, day; DE, delayed everolimus; EVR, everolimus; FPIA, fluorescence polarization immunoassay; FUP, follow-up; HPLC, high-performance liquid chromatography; IE, immediate everolimus; M, month; Myf, myfortic; scr, screening.
FIGURE 2.
FIGURE 2.
Patient disposition. EVR, everolimus; ITT, intent-to-treat; pts, patients.
FIGURE 3.
FIGURE 3.
Kaplan-Meier curve of time to first wound healing complication during the first 3 mo after transplantation: worst-case scenario approach (intent-to-treat population). Nr. at Risk, number at risk.
FIGURE 4.
FIGURE 4.
Kaplan-Meier curve of time to first wound healing complication during the first 3 mo after transplantation: best-case scenario approach (intent-to-treat population).
FIGURE 5.
FIGURE 5.
Kaplan-Meier curve of time to first wound healing complication during the 12 mo after transplantation: worst-case scenario approach (intent-to-treat population).
FIGURE 6.
FIGURE 6.
Kaplan-Meier curve of time to first wound healing complication during the 12 mo after transplantation: best-case scenario approach (intent-to-treat population).
FIGURE 7.
FIGURE 7.
Patient survival analysis during the first 12 mo after transplantation: Kaplan-Meier curve (intent-to-treat population).
FIGURE 8.
FIGURE 8.
Graft survival analysis during the first 12 mo after transplantation: Kaplan-Meier curve (intent-to-treat population).
See this image and copyright information in PMC

References

    1. Pascual J. Everolimus in clinical practice--renal transplantation. Nephrol Dial Transplant 200621Suppl 3iii18–iii23 - PubMed
    1. Nashan B. Induction therapy and mTOR inhibition: minimizing calcineurin inhibitor exposure in de novo renal transplant patients. Clin Transplant 201327Suppl 2516–29 - PubMed
    1. Budde K, Zeier M, Witzke O, et al. ; HERAKLES Study Group Everolimus with cyclosporine withdrawal or low-exposure cyclosporine in kidney transplantation from month 3: a multicentre, randomized trial. Nephrol Dial Transplant 2017321060–1070 - PubMed
    1. Carmellini M, Collini A, Ruggieri G, et al. Excellent long-term results in de novo renal transplant recipients treated with proliferation signal inhibitors and reduced calcineurin inhibitors exposure. Transplant Proc 2008401858–1861 - PubMed
    1. Ponticelli C, Scolari MP. Calcineurin inhibitors in renal transplantation still needed but in reduced doses: a review. Transplant Proc 2010422205–2208 - PubMed

Publication types

MeSH terms