Hypothermic Oxygenated Perfusion Versus Static Cold Storage for Expanded Criteria Donors in Liver and Kidney Transplantation: Protocol for a Single-Center Randomized Controlled Trial

Abstract

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: Extended criteria donors (ECD) are widely utilized due to organ shortage, but they may increase the risk of graft dysfunction and of poorer outcomes. Hypothermic oxygenated perfusion (HOPE) is a recent organ preservation strategy for marginal kidney and liver grafts, allowing to redirect anaerobic metabolism to aerobic metabolism under hypothermic conditions and to protect grafts from oxidative species-related damage; these mechanisms may potentially improve graft function and survival. Objective: With the present study we will evaluate the benefit of end-ischemic HOPE on ECD grafts (livers and kidneys) as compared to static cold storage (SCS). The aim of the study will be demonstrating the ability of HOPE to improve graft function and post-operative outcomes of ECD kidney and liver recipients. Methods: This is an open-label, randomized single center clinical trial with the aim of comparing HOPE vs. SCS in ECD kidney and liver transplantation. In the study protocol - approved by ethics committee - 220 patients (110 liver recipients and 110 kidney recipients) will be enrolled. Livers and kidneys assigned to HOPE will be perfused by machine perfusion with cold Belzer solution (4°-10°C) and with continuous oxygenation (partial pressure of oxygen = 500-600 mmHg). In the control group, livers and kidneys undergoing SCS will be steeped in Celsior or University of Wisconsin Belzer solutions and stored in ice. Using the same perfusion machine for both liver and kidney grafts, organs will be perfused from the start of the back-table procedure until implantation, without increasing cold ischemia time (CIT). For each group we will evaluate clinical outcomes, graft function tests and histologic findings, as well as perfusate and the number of allocated organs. Publication of the results may be assumed starting from 2021. Results: The dynamic preservation methods for organs from high-risk donors should improve the graft dysfunction after transplantation. The study is ongoing, and recruitment of participants will continue until January 2020. Conclusions: It is expected that the use of adequate organ preservation techniques may improve the post-transplant outcome without to compromise the graft function and survival increasing the donor organ pool. If proven effective, this method could be implemented in general practice. Clinical Trial: ClinicalTrials.gov NCT03837197; https://clinicaltrials.gov/ct2/show/NCT03837197?term=NCT03837197&rank=1 (Archived by WebCite® at http://www.webcitation.org/76fSutT3R)