Viability testing and transplantation of marginal livers (VITTAL) using normothermic machine perfusion: study protocol for an open-label, non-randomised, prospective, single-arm trial

Richard W Laing; Hynek Mergental; Christina Yap; Amanda Kirkham; Manpreet Whilku; Darren Barton; Stuart Curbishley; Yuri L Boteon; Desley A Neil; Stefan G Hübscher; M Thamara P R Perera; Paolo Muiesan; John Isaac; Keith J Roberts; Hentie Cilliers; Simon C Afford; Darius F Mirza

doi:10.1136/bmjopen-2017-017733

Viability testing and transplantation of marginal livers (VITTAL) using normothermic machine perfusion: study protocol for an open-label, non-randomised, prospective, single-arm trial

Richard W Laing, Hynek Mergental, Christina Yap, Amanda Kirkham, Manpreet Whilku, Darren Barton, Stuart Curbishley, Yuri L Boteon, Desley A Neil, Stefan G Hübscher, M Thamara P R Perera, Paolo Muiesan, John Isaac, Keith J Roberts, Hentie Cilliers, Simon C Afford, Darius F Mirza

Research output: Contribution to journal › Article › peer-review

51 Citations (Scopus)

136 Downloads (Pure)

Abstract

INTRODUCTION: The use of marginal or extended criteria donor livers is increasing. These organs carry a greater risk of initial dysfunction and early failure, as well as inferior long-term outcomes. As such, many are rejected due to a perceived risk of use and use varies widely between centres. Ex situ normothermic machine perfusion of the liver (NMP-L) may enable the safe transplantation of organs that meet defined objective criteria denoting their high-risk status and are currently being declined for use by all the UK transplant centres.

METHODS AND ANALYSIS: Viability testing and transplantation of marginal livers is an open-label, non-randomised, prospective, single-arm trial designed to determine whether currently unused donor livers can be salvaged and safely transplanted with equivalent outcomes in terms of patient survival. The procured rejected livers must meet predefined criteria that objectively denote their marginal condition. The liver is subjected to NMP-L following a period of static cold storage. Organs metabolising lactate to ≤2.5 mmol/L within 4 hours of the perfusion commencing in combination with two or more of the following parameters-bile production, metabolism of glucose, a hepatic arterial flow rate ≥150 mL/min and a portal venous flow rate ≥500 mL/min, a pH ≥7.30 and/or maintain a homogeneous perfusion-will be considered viable and transplanted into a suitable consented recipient. The coprimary outcome measures are the success rate of NMP-L to produce a transplantable organ and 90-day patient post-transplant survival.

ETHICS AND DISSEMINATION: The protocol was approved by the National Research Ethics Service (London-Dulwich Research Ethics Committee, 16/LO/1056), the Medicines and Healthcare Products Regulatory Agency and is endorsed by the National Health Service Blood and Transplant Research, Innovation and Novel Technologies Advisory Group. The findings of this trial will be disseminated through national and international presentations and peer-reviewed publications.

TRIAL REGISTRATION NUMBER: NCT02740608; Pre-results.

Original language	English
Article number	e017733
Journal	BMJ open
Volume	7
Issue number	11
DOIs	https://doi.org/10.1136/bmjopen-2017-017733
Publication status	Published - 28 Nov 2017

Keywords

hepatobiliary disease
hepatobiliary tumours
hepatology
transplant surgery

Access to Document

10.1136/bmjopen-2017-017733Licence: Creative Commons: Attribution (CC BY)

Laing_et_al_2017_Viability_testing_transplantation_BMJ_OpenFinal published version, 2.11 MBLicence: Creative Commons: Attribution (CC BY)

Cite this

Laing, R. W., Mergental, H., Yap, C., Kirkham, A., Whilku, M., Barton, D., Curbishley, S., Boteon, Y. L., Neil, D. A., Hübscher, S. G., Perera, M. T. P. R., Muiesan, P., Isaac, J., Roberts, K. J., Cilliers, H., Afford, S. C., & Mirza, D. F. (2017). Viability testing and transplantation of marginal livers (VITTAL) using normothermic machine perfusion: study protocol for an open-label, non-randomised, prospective, single-arm trial. BMJ open, 7(11), Article e017733. https://doi.org/10.1136/bmjopen-2017-017733

@article{5d887260ee054326a691167280b4175a,

title = "Viability testing and transplantation of marginal livers (VITTAL) using normothermic machine perfusion: study protocol for an open-label, non-randomised, prospective, single-arm trial",

abstract = "INTRODUCTION: The use of marginal or extended criteria donor livers is increasing. These organs carry a greater risk of initial dysfunction and early failure, as well as inferior long-term outcomes. As such, many are rejected due to a perceived risk of use and use varies widely between centres. Ex situ normothermic machine perfusion of the liver (NMP-L) may enable the safe transplantation of organs that meet defined objective criteria denoting their high-risk status and are currently being declined for use by all the UK transplant centres.METHODS AND ANALYSIS: Viability testing and transplantation of marginal livers is an open-label, non-randomised, prospective, single-arm trial designed to determine whether currently unused donor livers can be salvaged and safely transplanted with equivalent outcomes in terms of patient survival. The procured rejected livers must meet predefined criteria that objectively denote their marginal condition. The liver is subjected to NMP-L following a period of static cold storage. Organs metabolising lactate to ≤2.5 mmol/L within 4 hours of the perfusion commencing in combination with two or more of the following parameters-bile production, metabolism of glucose, a hepatic arterial flow rate ≥150 mL/min and a portal venous flow rate ≥500 mL/min, a pH ≥7.30 and/or maintain a homogeneous perfusion-will be considered viable and transplanted into a suitable consented recipient. The coprimary outcome measures are the success rate of NMP-L to produce a transplantable organ and 90-day patient post-transplant survival.ETHICS AND DISSEMINATION: The protocol was approved by the National Research Ethics Service (London-Dulwich Research Ethics Committee, 16/LO/1056), the Medicines and Healthcare Products Regulatory Agency and is endorsed by the National Health Service Blood and Transplant Research, Innovation and Novel Technologies Advisory Group. The findings of this trial will be disseminated through national and international presentations and peer-reviewed publications.TRIAL REGISTRATION NUMBER: NCT02740608; Pre-results.",

keywords = "hepatobiliary disease, hepatobiliary tumours, hepatology, transplant surgery",

author = "Laing, {Richard W} and Hynek Mergental and Christina Yap and Amanda Kirkham and Manpreet Whilku and Darren Barton and Stuart Curbishley and Boteon, {Yuri L} and Neil, {Desley A} and H{\"u}bscher, {Stefan G} and Perera, {M Thamara P R} and Paolo Muiesan and John Isaac and Roberts, {Keith J} and Hentie Cilliers and Afford, {Simon C} and Mirza, {Darius F}",

note = "{\textcopyright} Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.",

year = "2017",

month = nov,

day = "28",

doi = "10.1136/bmjopen-2017-017733",

language = "English",

volume = "7",

journal = "BMJ open",

issn = "2044-6055",

publisher = "BMJ Publishing Group",

number = "11",

}

Laing, RW, Mergental, H, Yap, C, Kirkham, A, Whilku, M, Barton, D, Curbishley, S, Boteon, YL, Neil, DA, Hübscher, SG, Perera, MTPR, Muiesan, P, Isaac, J, Roberts, KJ, Cilliers, H, Afford, SC & Mirza, DF 2017, 'Viability testing and transplantation of marginal livers (VITTAL) using normothermic machine perfusion: study protocol for an open-label, non-randomised, prospective, single-arm trial', BMJ open, vol. 7, no. 11, e017733. https://doi.org/10.1136/bmjopen-2017-017733

TY - JOUR

T1 - Viability testing and transplantation of marginal livers (VITTAL) using normothermic machine perfusion

T2 - study protocol for an open-label, non-randomised, prospective, single-arm trial

AU - Laing, Richard W

AU - Mergental, Hynek

AU - Yap, Christina

AU - Kirkham, Amanda

AU - Whilku, Manpreet

AU - Barton, Darren

AU - Curbishley, Stuart

AU - Boteon, Yuri L

AU - Neil, Desley A

AU - Hübscher, Stefan G

AU - Perera, M Thamara P R

AU - Muiesan, Paolo

AU - Isaac, John

AU - Roberts, Keith J

AU - Cilliers, Hentie

AU - Afford, Simon C

AU - Mirza, Darius F

PY - 2017/11/28

Y1 - 2017/11/28

N2 - INTRODUCTION: The use of marginal or extended criteria donor livers is increasing. These organs carry a greater risk of initial dysfunction and early failure, as well as inferior long-term outcomes. As such, many are rejected due to a perceived risk of use and use varies widely between centres. Ex situ normothermic machine perfusion of the liver (NMP-L) may enable the safe transplantation of organs that meet defined objective criteria denoting their high-risk status and are currently being declined for use by all the UK transplant centres.METHODS AND ANALYSIS: Viability testing and transplantation of marginal livers is an open-label, non-randomised, prospective, single-arm trial designed to determine whether currently unused donor livers can be salvaged and safely transplanted with equivalent outcomes in terms of patient survival. The procured rejected livers must meet predefined criteria that objectively denote their marginal condition. The liver is subjected to NMP-L following a period of static cold storage. Organs metabolising lactate to ≤2.5 mmol/L within 4 hours of the perfusion commencing in combination with two or more of the following parameters-bile production, metabolism of glucose, a hepatic arterial flow rate ≥150 mL/min and a portal venous flow rate ≥500 mL/min, a pH ≥7.30 and/or maintain a homogeneous perfusion-will be considered viable and transplanted into a suitable consented recipient. The coprimary outcome measures are the success rate of NMP-L to produce a transplantable organ and 90-day patient post-transplant survival.ETHICS AND DISSEMINATION: The protocol was approved by the National Research Ethics Service (London-Dulwich Research Ethics Committee, 16/LO/1056), the Medicines and Healthcare Products Regulatory Agency and is endorsed by the National Health Service Blood and Transplant Research, Innovation and Novel Technologies Advisory Group. The findings of this trial will be disseminated through national and international presentations and peer-reviewed publications.TRIAL REGISTRATION NUMBER: NCT02740608; Pre-results.

AB - INTRODUCTION: The use of marginal or extended criteria donor livers is increasing. These organs carry a greater risk of initial dysfunction and early failure, as well as inferior long-term outcomes. As such, many are rejected due to a perceived risk of use and use varies widely between centres. Ex situ normothermic machine perfusion of the liver (NMP-L) may enable the safe transplantation of organs that meet defined objective criteria denoting their high-risk status and are currently being declined for use by all the UK transplant centres.METHODS AND ANALYSIS: Viability testing and transplantation of marginal livers is an open-label, non-randomised, prospective, single-arm trial designed to determine whether currently unused donor livers can be salvaged and safely transplanted with equivalent outcomes in terms of patient survival. The procured rejected livers must meet predefined criteria that objectively denote their marginal condition. The liver is subjected to NMP-L following a period of static cold storage. Organs metabolising lactate to ≤2.5 mmol/L within 4 hours of the perfusion commencing in combination with two or more of the following parameters-bile production, metabolism of glucose, a hepatic arterial flow rate ≥150 mL/min and a portal venous flow rate ≥500 mL/min, a pH ≥7.30 and/or maintain a homogeneous perfusion-will be considered viable and transplanted into a suitable consented recipient. The coprimary outcome measures are the success rate of NMP-L to produce a transplantable organ and 90-day patient post-transplant survival.ETHICS AND DISSEMINATION: The protocol was approved by the National Research Ethics Service (London-Dulwich Research Ethics Committee, 16/LO/1056), the Medicines and Healthcare Products Regulatory Agency and is endorsed by the National Health Service Blood and Transplant Research, Innovation and Novel Technologies Advisory Group. The findings of this trial will be disseminated through national and international presentations and peer-reviewed publications.TRIAL REGISTRATION NUMBER: NCT02740608; Pre-results.

KW - hepatobiliary disease

KW - hepatobiliary tumours

KW - hepatology

KW - transplant surgery

U2 - 10.1136/bmjopen-2017-017733

DO - 10.1136/bmjopen-2017-017733

M3 - Article

C2 - 29183928

SN - 2044-6055

VL - 7

JO - BMJ open

JF - BMJ open

IS - 11

M1 - e017733

ER -

Viability testing and transplantation of marginal livers (VITTAL) using normothermic machine perfusion: study protocol for an open-label, non-randomised, prospective, single-arm trial

Abstract

Keywords

Access to Document

Fingerprint

Cite this