Abstract
BackgroundLiver transplantation is the best treatment for end-stage liver disease. The interruption of the blood supply to the donor liver during cold storage damages the liver, affecting how well the liver will function after transplant. The drug Simvastatin may help to protect donor livers against this damage and improve outcomes for transplant recipients. The aim of this study is to evaluate the benefits of treating the donor liver with Simvastatin compared with the standard transplant procedure.Patient and methodsWe propose a prospective, double-blinded, randomized phase 2 study of 2 parallel groups of eligible adult patients. We will compare 3-month, 6-month, and 12-month graft survival after LT, in order to identify a significant relation between the two homogenous groups of LT patients. The two groups only differ by the Simvastatin or placebo administration regimen while following the same procedure, with identical surgical instruments, and medical and nursing skilled staff. To reach these goals, we determined that we needed to recruit 106 patients. This sample size achieves 90% power to detect a difference of 14.6% between the two groups survival using a one-sided binomial test.DiscussionThis trial is designed to confirm the effectiveness of Simvastatin to protect healthy and steatotic livers undergoing cold storage and warm reperfusion before transplantation and to evaluate if the addition of Simvastatin translates into improved graft outcomes.Trial registrationISRCTN27083228.
Highlights
Liver transplantation is the best treatment for end-stage liver disease
Ischemia/reperfusion (I/R) injury during the conventional cold storage and preservation of donated livers is a key determinant of graft function after Liver transplantation (LT)
Hypoxia and reperfusion activate innate mechanisms of inflammation that cause injury and underline delayed graft function. [1,2,3] I/R injury causes almost 10% of early organ failure and can lead to the higher incidence of both acute and chronic rejection. [4, 5] Simvastatin suppresses the inflammatory effect in vascular endothelial cells, thereby protecting the liver against I/R injury and its effects on grafts from extended-criteria donors. [6,7,8,9] Statins or HMG-CoA inhibitors were primarily designed to decrease cholesterol levels
Summary
Liver transplantation is the best treatment for end-stage liver disease. The interruption of the blood supply to the donor liver during cold storage damages the liver, affecting how well the liver will function after transplant. The two groups only differ by the Simvastatin or placebo administration regimen while following the same procedure, with identical surgical instruments, and medical and nursing skilled staff. To reach these goals, we determined that we needed to recruit 106 patients. The differences will be obtained with neither a complex therapeutic approach of combining different pharmacologic strategies nor the usage of machine perfusion methods, but by the sole cost of a single drug/placebo administration In this novel approach, the infusion of Simvastatin will be applied directly into the donor liver’s portal vein after donor hepatectomy. The clinical trial allows avoidance of systemic infusion, so the protocol could be applied in cases of multiorgan deceased donor retrievals
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