The addition of simvastatin administration to cold storage solution of explanted whole liver grafts for facing ischemia/reperfusion injury in an area with a low rate of deceased donation: a monocentric randomized controlled double-blinded phase 2 study

BMC Surg. 2018 Dec 27;18(1):122. doi: 10.1186/s12893-018-0455-7.

Abstract

Background: 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 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 methods: We 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.

Discussion: This 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 registration: ISRCTN27083228 .

Keywords: Donor after brain death; Ischemia/reperfusion injury; Liver transplantation; Simvastatin.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Clinical Trials, Phase II as Topic
  • Double-Blind Method
  • Fatty Liver / pathology
  • Humans
  • Liver / drug effects
  • Liver / pathology
  • Liver Transplantation* / methods
  • Organ Preservation Solutions / chemistry
  • Organ Preservation* / methods
  • Prospective Studies
  • Protective Agents / administration & dosage
  • Protective Agents / pharmacology
  • Randomized Controlled Trials as Topic
  • Reperfusion Injury / prevention & control
  • Simvastatin* / pharmacology

Substances

  • Protective Agents
  • Simvastatin
  • Organ Preservation Solutions