Viability Testing and Transplantation of Marginal Livers

NCT02740608 | Completed DMC

• 2 other identifiers: RG_15_2402016-001250-18
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to determine if a rejected liver is viable using normothermic machine liver perfusion (NMLP). It aims to

1. 1.establish the suitability of livers which have been declined by all UK liver transplant centres by monitoring their function on the NMLP machine; and,
2. 2.transplant the liver if its function on the machine is satisfactory allowing it to be transplanted.

Conditions

Liver Transplantation

Outcome Measures

Primary Outcomes (2)

• Patient survival

  Achievement of successful transplantation of previously rejected donor liver following viability testing using NMLP

  90 days

• Use of NMLP to identify the proportion of transplantable liver grafts from the currently rejected donor organ pool.

  Decision point of using graft in patient transplantation

  Approximately 6 hours

Secondary Outcomes (3)

• Liver graft function

  12 month

• Morbidity associated with receipt of extended criteria graft

  90 days

• Physiological response to reperfusion of the perfused grafts

  Approximately 6 hours

Study Arms (1)

Liver transplantation

OTHER

All Participants will receive liver transplantation using the OrganOx metra device

Device: OrganOx metra

Interventions

OrganOx metra DEVICE

Normothermic Machine Liver Perfusion

Liver transplantation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Liver from a donor primary accepted with the intention for a clinical transplantation
• Liver graft was rejected by all the other UK transplant centres via normal or fast-track sequence
• Cold ischaemic time less than 16 hours for DBD and 10 hours for DCD grafts
• One of the following parameters capturing the objectivity of the liver high-risk status
• Donor risk index greater than 2.0
• Graft steatosis greater than 30%
• BAR score greater than 9;
• Donor warm ischaemic time greater than 30 minutes
• Anticipated cold ischaemic time greater than 12 hours for DBD or 8 hours for DCD liver grafts
• Suboptimal liver graft perfusion documented by a photo of macroscopic appearance
• Liver transaminases (ALT or AST) above 1000 IU/mL

You may not qualify if:

• Grafts from patients with active Hepatitis B, C or HIV infection
• Livers with cirrhotic macroscopic appearance
• Livers with advanced fibrosis
• DCD grafts with donor warm ischaemic time (systolic blood pressure less than 50mmHg to aortic perfusion) more than 60 minutes
• Excessive cold ischaemic times (DBD more than 16 hours / DCD more than 10 hours)
• Criteria for transplantation:
• Evidence of bile production
• Perfusate lactate levels less than or equal to 2.5 mmol/L 3. pH greater than 7.30
• \. Metabolism of glucose 5. Stable arterial flow of more than 150 mL/ minute and portal flow more than 500 mL/minute 6. Homogeneous graft perfusion with soft consistency of the parenchyma
• Adult primary liver transplant recipient
• Patient listed electively for transplantation
• Low to moderate transplant risk candidate, suitable for marginal graft, as assessed by the UHB liver transplant listing MDT meeting (these are usually candidates with low UKELD score, without cardiovascular comorbidities, with good functional and nutrition status, with patent portal vein and with no history of previous major upper abdominal surgery, e.g. patients transplanted for liver cancer)
• High-risk patients and recipients not suitable for a marginal graft (these are mainly patients with high UKELD score (\>62 as per the NHSBT LAG criteria for graft sharing in highrisks recipients in the North East of the UK \[http://www.odt.nhs.uk/pdf/advisory.../Liver\_National\_Allocation\_Scheme.pdf\]), with cardiovascular comorbidities or renal insufficiency, with poor nutrition and performance status or history of major upper abdominal surgery, e.g. patients listed for liver re-transplantation)
• Patients with complete portal vein thrombosis diagnosed prior to the transplantation
• Liver re-transplantation

Sponsors & Collaborators

• University of Birmingham: lead
• Wellcome Trust: collaborator
• University Hospital Birmingham NHS Foundation Trust: collaborator

Study Sites (1)

UHBFT - Queen Elizabeth Hospital, Birmingham

Birmingham, B15 2TT, United Kingdom

Location

Related Publications (7)

• Laing RW, Mergental H, Yap C, Kirkham A, Whilku M, Barton D, Curbishley S, Boteon YL, Neil DA, Hubscher SG, Perera MTPR, Muiesan P, Isaac J, Roberts KJ, Cilliers H, Afford SC, Mirza DF. 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. 2017 Nov 28;7(11):e017733. doi: 10.1136/bmjopen-2017-017733.

  PMID: 29183928 BACKGROUND

• Mergental H, Laing RW, Hodson J, Boteon YL, Attard JA, Walace LL, Neil DAH, Barton D, Schlegel A, Muiesan P, Abradelo M, Isaac JR, Roberts K, Perera MTPR, Afford SC, Mirza DF. Introduction of the Concept of Diagnostic Sensitivity and Specificity of Normothermic Perfusion Protocols to Assess High-Risk Donor Livers. Liver Transpl. 2022 May;28(5):794-806. doi: 10.1002/lt.26326. Epub 2021 Nov 9.

  PMID: 34619014 BACKGROUND

• Mergental H, Laing RW, Afford SC, Mirza DF. Reply to 'Hypothermic machine perfusion before viability testing of previously discarded human livers'. Nat Commun. 2021 Feb 12;12(1):1015. doi: 10.1038/s41467-021-21183-7. No abstract available.

  PMID: 33579911 BACKGROUND

• Neil DAH, Mergental H, Hann A, Laing RW, Hartog H, Mirza DF, Perera MTPR. Is Hepatocyte Necrosis a Good Marker of Donor Liver Viability During Machine Perfusion? Hepatol Commun. 2022 Feb;6(2):435-436. doi: 10.1002/hep4.1816. Epub 2021 Sep 2. No abstract available.

  PMID: 34558864 BACKGROUND

• Attard JA, Osei-Bordom DC, Boteon Y, Wallace L, Ronca V, Reynolds G, Perera MTPR, Oo YH, Mergental H, Mirza DF, Afford SC. Ex situ Normothermic Split Liver Machine Perfusion: Protocol for Robust Comparative Controls in Liver Function Assessment Suitable for Evaluation of Novel Therapeutic Interventions in the Pre-clinical Setting. Front Surg. 2021 Feb 17;8:627332. doi: 10.3389/fsurg.2021.627332. eCollection 2021.

  PMID: 33681282 BACKGROUND

• Mergental H, Laing RW, Kirkham AJ, Perera MTPR, Boteon YL, Attard J, Barton D, Curbishley S, Wilkhu M, Neil DAH, Hubscher SG, Muiesan P, Isaac JR, Roberts KJ, Abradelo M, Schlegel A, Ferguson J, Cilliers H, Bion J, Adams DH, Morris C, Friend PJ, Yap C, Afford SC, Mirza DF. Transplantation of discarded livers following viability testing with normothermic machine perfusion. Nat Commun. 2020 Jun 16;11(1):2939. doi: 10.1038/s41467-020-16251-3.

  PMID: 32546694 RESULT

• Mergental H, Laing RW, Kirkham AJ, Clarke G, Boteon YL, Barton D, Neil DAH, Isaac JR, Roberts KJ, Abradelo M, Schlegel A, Dasari BVM, Ferguson JW, Cilliers H, Morris C, Friend PJ, Yap C, Afford SC, Perera MTPR, Mirza DF. Discarded livers tested by normothermic machine perfusion in the VITTAL trial: Secondary end points and 5-year outcomes. Liver Transpl. 2024 Jan 1;30(1):30-45. doi: 10.1097/LVT.0000000000000270. Epub 2023 Dec 15.

  PMID: 38109282 DERIVED

Study Officials

• Darius Mirza

  University Hospital Birmingham NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2016
• First Posted: April 15, 2016
• Study Start: October 6, 2016
• Primary Completion: May 8, 2018
• Study Completion: March 1, 2020
• Last Updated: March 11, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)