Efficacy Evaluation of Normothermic Perfusion Machine Preservation in Liver Transplant Using Very Old Donors

Ischemic Reperfusion Injury Clinical Trial

— CEFEMA  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02940600
• Other study ID #: 687
• Status: Recruiting
• Phase: N/A
• First received: October 16, 2016
• Last updated: October 19, 2016
• Start date: October 2016
• Est. completion date: October 2018

Study information

• Verified date: October 2016
• Source: Azienda Ospedaliero, Universitaria Pisana
• Contact: Davide Ghinolfi, MD, PhD
• Phone: +39050995421
• Email: d.ghinolfi[@]ao-pisa.toscana.it
• Is FDA regulated: No
• Health authority: Italy: National Institute of Health
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: October 2018
• Est. primary completion date: April 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ischemic Reperfusion Injury
• Reperfusion Injury

Intervention

Device:
• Normothermic machine perfusion
Patients undergoing liver transplant with the use of grafts preserved with normothermic perfusion machine

Procedure:
• Static cold storage
Patients undergoing liver transplant using statically cold preserved grafts

Locations

Country	Name	City	State
Italy	UO Chirurgia Epatica e del Trapianto di Fegato	Pisa

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliero, Universitaria Pisana

Country where clinical trial is conducted

Italy, 

References & Publications (4)

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 Centre Canadian Experience of Human Normothermic Ex Vivo Liver Perfusion: Results of a Clinical Trial. Am J Transplant. 2016 Sep 17. doi: 10.1111/ajt.14049. [Epub ahead of print] — View Citation

Mergental H, Perera MT, Laing RW, Muiesan P, Isaac JR, Smith A, Stephenson BT, Cilliers H, Neil DA, Hübscher SG, Afford SC, Mirza DF. Transplantation of Declined Liver Allografts Following Normothermic Ex-Situ Evaluation. Am J Transplant. 2016 May 19. doi: 10.1111/ajt.13875. [Epub ahead of print] — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	6 months graft survival		180 days	Yes
Secondary	Ischemia-reperfusion injury assessment through biopsies evaluation		1 day	No
Secondary	ischemia reperfusion injury assessment through transaminases	AST level at post operative day number 7	7 days	No
Secondary	Ischemia reperfusion injury assessment through incidence of ischemic type biliary lesions		180 days	No