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
Duilio Pagano,
Elisabetta Oliva,
Simone Khouzam,
Fabio Tuzzolino,
Davide Cintorino,
Sergio Li Petri,
Fabrizio di Francesco,
Calogero Ricotta,
Pasquale Bonsignore,
Alessandro Tropea,
Sergio Calamia,
Federico Costanzo,
Angelo Luca,
Salvatore Gruttadauria
Affiliations
Duilio Pagano
Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT (Istituto di Ricovero e Cura a Carattere Scientifico - Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center) Italy
Elisabetta Oliva
Fondazione Ri.MED
Simone Khouzam
Sidney Kimmel Medical College - Thomas Jefferson University
Fabio Tuzzolino
Research Office, IRCCS-ISMETT, UPMC Italy
Davide Cintorino
Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT (Istituto di Ricovero e Cura a Carattere Scientifico - Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center) Italy
Sergio Li Petri
Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT (Istituto di Ricovero e Cura a Carattere Scientifico - Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center) Italy
Fabrizio di Francesco
Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT (Istituto di Ricovero e Cura a Carattere Scientifico - Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center) Italy
Calogero Ricotta
Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT (Istituto di Ricovero e Cura a Carattere Scientifico - Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center) Italy
Pasquale Bonsignore
Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT (Istituto di Ricovero e Cura a Carattere Scientifico - Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center) Italy
Alessandro Tropea
Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT (Istituto di Ricovero e Cura a Carattere Scientifico - Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center) Italy
Sergio Calamia
Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT (Istituto di Ricovero e Cura a Carattere Scientifico - Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center) Italy
Federico Costanzo
Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT (Istituto di Ricovero e Cura a Carattere Scientifico - Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center) Italy
Angelo Luca
Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT, UPMC Italy
Salvatore Gruttadauria
Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT (Istituto di Ricovero e Cura a Carattere Scientifico - Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center) Italy
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.