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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.
- hepatobiliary disease
- hepatology
- hepatobiliary tumours
- transplant surgery
- transplant surgery
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Footnotes
Contributors DFM (chief investigator) and HM (principal investigator) had the original concept of the VITTAL trial following on from a successful pilot study. DFM, HM, RWL, AK, CY and designed the VITTAL trial. RWL, MW, AK, and HM wrote the protocol and IRAS applications. DB, HM, SCA, PF and DFM reviewed all protocol versions. RWL, MW and DB (senior trials coordinator) submitted all REC, MHRA, HRA, NHSBT and local R&D applications. HM, AK, DFM and CY devised the statistical plan. TP, PM, JI, KR, HM and DFM are the transplant surgeons involved in the trial. RWL and MW wrote the patient information sheets, external trial information and patient CRFs. RWL, HM and DFM wrote the manuscript and all authors reviewed the final version.
Funding This trial is funded by a grant awarded by the Wellcome Trust Health Innovation Challenge Fund (awarded in December 2015). The grant application was a joint effort of the coapplicant team (Darius Mirza, Hynek Mergental, Simon Afford, David Adams, Peter Friend, Stefan Hübscher, Julian Bion, Christina Yap) and collaborators (Paolo Muiesan, Thamara Perera, Hentie Cilliers, Ricky Bhogal, Richard Laing, Amanda Kirkham, James Ferguson, Desley Neil, Amanda Smith, Steven Youngs, Darren Barton and Leslie Russell). The project was endorsed and supported by all the clinical staff at the Liver Unit of UHBFT and we would like to thank everybody for their hard work and dedication to the transplant programme. RWL, YB and SCA have received support from the NIHR Birmingham Liver Biomedical Research Unit.
Disclaimer The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.
Competing interests RWL and YB receive salary as Wellcome Trust research fellows.
Ethics approval London-Dulwich (16/LO/1056)
Provenance and peer review Not commissioned; externally peer reviewed.