Clinical trial NCT02940600: Efficacy Evaluation of Normothermic Perfusion Machine Preservation in Liver Transplant Using Very Old Donors
Official title: Pilot, Open, Monocentric, Randomized, Prospective Trial for the Evaluation of the Efficacy of Normothermic Perfusion Machine for Organ Preservation in Liver Transplantation Using Brain Death Donors Older or Equal Than 70 Years
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Ischemic Reperfusion Injury
Keywords: normothermic perfusion
old donors
extended criteria grafts
reconditioning
Lead sponsor: Azienda Ospedaliero, Universitaria Pisana
Sponsor class: OTHER
First posted: 2016-10-21
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the impact of normothermic machine perfusion in liver transplantation using grafts of brain death donors older or equal than 70 years

Detailed description: Mean donor age for liver transplantation in Tuscany, Italy, is increasing and is actually 71 years. Old donors are a valuable resource but their use has been related to a major incidence of primary non function (PNF), delayed graft function (DGF) and ischemic type biliary lesions (ITBL).

Ischemia-reperfusion injury is a major reason for the development of these complications and and old grafts are more susceptible than younger ones.

Normothermic machine perfusion (NMP) is a novel and promising technique that allows preservation in a more physiological environment. It is our belief that the use of NMP might reduce the impact of ischemia-reperfusion injuries in older grafts thus reducing the incidence of complications and providing a better outcome.

Eligibility criteria: Inclusion Criteria:

* Patient on waiting list for liver transplant
* Signed informed consent
* Age between 18 and 70
* Eligibility for liver transplant as for University of Pisa Liver Transplant Center Protocol
* Capacity and willingness to participate to the protocol

Exclusion Criteria:

* No signed informed consent
* Age under 18 or over 70
* Presence of disease that may influence results
* Patient participation to other studies
* Re-liver transplant
* ABO incompatible OLT
* Multiorgan transplant
* Liver transplant for acute liver failure or trauma
* MELD (model for end stage liver disease) \>24
* Patient not suitable to participate on investigators's opinion

Primary outcomes:
measure: 6 months graft survival
timeFrame: 180 days
Secondary outcomes:
measure: Ischemia-reperfusion injury assessment through biopsies evaluation
timeFrame: 1 day
measure: ischemia reperfusion injury assessment through transaminases
timeFrame: 7 days
measure: Ischemia reperfusion injury assessment through incidence of ischemic type biliary lesions
timeFrame: 180 days
Other outcomes:
Locations:
city: Pisa
country: Italy
facility: UO Chirurgia Epatica e del Trapianto di Fegato
Study officials:
affiliation: Azienda Ospedaliero, Universitaria Pisana
name: Davide Ghinolfi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bral M, Gala-Lopez B, Bigam D, Kneteman N, Malcolm A, Livingstone S, Andres A, Emamaullee J, Russell L, Coussios C, West LJ, Friend PJ, Shapiro AM. Preliminary Single-Center Canadian Experience of Human Normothermic Ex Vivo Liver Perfusion: Results of a Clinical Trial. Am J Transplant. 2017 Apr;17(4):1071-1080. doi: 10.1111/ajt.14049. Epub 2016 Dec 9.
citation: Mergental H, Perera MT, Laing RW, Muiesan P, Isaac JR, Smith A, Stephenson BT, Cilliers H, Neil DA, Hubscher SG, Afford SC, Mirza DF. Transplantation of Declined Liver Allografts Following Normothermic Ex-Situ Evaluation. Am J Transplant. 2016 Nov;16(11):3235-3245. doi: 10.1111/ajt.13875. Epub 2016 Jul 13.
citation: Op den Dries S, Karimian N, Westerkamp AC, Sutton ME, Kuipers M, Wiersema-Buist J, Ottens PJ, Kuipers J, Giepmans BN, Leuvenink HG, Lisman T, Porte RJ. Normothermic machine perfusion reduces bile duct injury and improves biliary epithelial function in rat donor livers. Liver Transpl. 2016 Jul;22(7):994-1005. doi: 10.1002/lt.24436.
citation: Ravikumar R, Jassem W, Mergental H, Heaton N, Mirza D, Perera MT, Quaglia A, Holroyd D, Vogel T, Coussios CC, Friend PJ. Liver Transplantation After Ex Vivo Normothermic Machine Preservation: A Phase 1 (First-in-Man) Clinical Trial. Am J Transplant. 2016 Jun;16(6):1779-87. doi: 10.1111/ajt.13708. Epub 2016 Mar 7.