The study investigates how machine preservation methods protect and repair donor livers, and aims to understand which methods work best and why, so more of these higher-risk livers can be safely used for transplants

ISRCTN	ISRCTN15444108
DOI	https://doi.org/10.1186/ISRCTN15444108
Integrated Research Application System (IRAS)	328606
Central Portfolio Management System (CPMS)	58963
Medical Research Council (MRC) grant code	MR/X019470/1
Sponsors	King's College London, King's College Hospital NHS Foundation Trust
Funder	Medical Research Council

Submission date: 07/04/2026
Registration date: 23/04/2026
Last edited: 07/05/2026

Recruitment status: No longer recruiting
Overall study status: Ongoing
Condition category: Digestive System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
There are not enough donated livers for everybody who needs one, and as a result, thousands of patients worldwide are waiting for liver transplants, with many dying while waiting for a life-saving organ. One reason for this shortage is that some usable livers from donors who are considered of high-risk are being thrown away out of concern that they might not work well after transplantation due to a problem called ischaemia reperfusion injury (IRI).

The discarded organs are mostly those coming from donors who have died due to cardiac arrest (called 'donation after circulatory death’ or DCD), with only 27% of them being used in the UK. The quality of these DCD organs could be improved by changing how they are preserved after being removed from the donor. The most commonly used strategy is still to remove the livers and put them in an icebox ('static cold storage' or SCS). The alternative approaches, which are more complex and expensive but can also improve the quality of the DCD livers, involve using machines to pump fluids through the livers ('machine perfusion' or MP).

Three MP methods are being used in patients: 1) normothermic regional perfusion (NRP), which involves pumping the donor's blood through the liver after the donor has died but the liver is still in the donor’s body; 2) normothermic machine perfusion (NMP), in which the liver is pumped with blood outside of the donor’s body; and 3) hypothermic machine perfusion (HOPE), which is also used outside of the donor’s body by pumping cold fluid into the liver. HOPE and NRP have been shown to improve how well DCD livers function after transplantation. NMP can also improve the quality of the DCD livers, but its main advantage is that it allows confirming that the donated liver functions well before proceeding with the transplant. Until now, there has not been a proper comparison of these methods, and we do not understand well the mechanisms through which MP improves the quality of the DCD livers.

The plan is to conduct a study where 36 DCD human livers will be split into three groups: SCS, NRP, and HOPE. After that, they will be put in NMP to confirm that they are good enough to be transplanted and to study the mechanisms through which NRP, SCS and HOPE work.

Who can participate?
Adult patients listed for elective liver transplantation.

What does the study involve?
This study tests three different ways of preserving donor livers from donors after circulatory death before transplantation. Donor livers are randomly assigned to standard cold storage, blood‑based regional perfusion in the donor, or oxygenated cold perfusion after retrieval, before all livers undergo normothermic machine perfusion and transplantation, where possible.

What are the possible benefits and risks of participating?
Benefits and risks not provided at time of registration

Where is the study run from?
Kings College Hospital, UK.

When is the study starting and how long is it expected to run for?
March 2025 to December 2026.

Who is funding the study?
King's College Hospital NHS Foundation Trust, UK.
Medical Research Council, UK.

Who is the main contact?
Prof Alberto Sanchez-Fueyo, sanchez_fueyo@kcl.ac.uk

Contact information

Prof Alberto Sanchez-Fueyo
Principal investigator, Public, Scientific

Kings College Hospital
Denmark Hill
London
SE5 9RS
United Kingdom

Phone	+44 02078486910
Email	sanchez_fueyo@kcl.ac.uk

Study information

Primary study design	Interventional
Allocation	Randomized controlled trial
Masking	Open (masking not used)
Control	Uncontrolled
Assignment	Single
Purpose	Device feasibility
Scientific title	Mechanistic evaluation of machine perfusion strategies in donation after circulatory death liver transplantation
Study acronym	iMAPS
Study objectives	Primary objective: To determine the effect of different preservation strategies on the development of mitochondrial damage following reperfusion. Secondary mechanistic and exploratory objectives: 1) To determine the effect of different preservation strategies on mitochondrial integrity using alternative analytical strategies. 2) To assess the overall cellular metabolic and redox state during NMP and after reperfusion in the transplant recipient. 3) To determine how the different preservation strategies impact on the levels of inflammatory mediators during NMP. 4) To determine the influence of the different preservation strategies on biomarkers of liver damage and function during NMP. 5) To compare the applicability of different preservation strategies in DCD liver transplantation. Secondary clinical objectives: 1) To determine the impact of the 3 different MP strategies on clinical outcomes up to 12 months following transplantation. 2) To develop objective means to assess the quality and suitability for transplantation of DCD livers. 3)To compare the applicability of different preservation strategies in DCD liver transplantation.
Ethics approval(s)	Approved 10/11/2023, West Midlands - South Birmingham Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 0207 104 8000; southbirmingham.rec@hra.nhs.uk), ref: 23/WM/0226
Health condition(s) or problem(s) studied	The patient population consists of adults listed for elective liver transplantation
Intervention	Open-label, prospective, three-arm, phase II randomized clinical trial investigating the effects of 3 different preservation techniques on pre-defined functional and mechanistic endpoints in DCD liver transplantation. Consecutive circulatory death donors (DCD) assigned to recipients consented to participate in the trial will be randomized to one of three arms (n=12 per arm): Arm 1 (Static cold storage: SCS). The donor liver will be flushed in situ with 4 °C UW preservation solution (or HTK) through the aorta and portal vein, retrieved, and transported to the transplant centre in an icebox. Arm 2 (Normothermic regional perfusion: NRP). The donor aorta and inferior cava vein will be cannulated, followed by descending thoracic aorta cross-clamp and initiation of perfusion (Cardiohelp device) with the donor’s own blood at 37 °C for 2 h (while monitoring pump flow, venous O2 saturation, lactate and ALT), followed by in-situ flush with 4 °C preservation solution as in the SCS arm. Arm 3 (Hypothermic oxygenated perfusion: HOPE). The liver will be retrieved and preserved as in the SCS arm. Then, on arrival to the transplant unit, the portal vein and hepatic artery will be cannulated, and the liver perfused with hypothermic oxygenated solution (VitaSmart device) for 2 h. All livers, regardless of their allocated Arm, will then be perfused under normothermic machine perfusion conditions for at least 4 h before transplantation. Primary analysis will be as per protocol and include all livers that are perfused under normothermic machine perfusion (NMP) conditions for at least 4 h. A secondary analysis including recipient outcomes will include only livers actually transplanted. The overall study duration will be up to 30 months. The study participant recruitment phase will last up to 18 months. Patient follow-up will be 12 months. Clinical outcome data will be collected up to 5 years post-transplant.
Intervention type	Device
Phase	Phase II
Drug / device / biological / vaccine name(s)	NRP (normothermic regional perfusion), SCS (static cold storage) and HOPE (hypothermic perfusion)
Primary outcome measure(s)	Ischaemia-Reperfusion injury (IRI) damage measured using a surrogate post-transplant clinical endpoint of IRI damage up to 12 months post-transplant, such as reperfusion syndrome, early allograft dysfunction (assessed by the Model for Early Allograft Function (MEAF) and Liver Graft Assessment following Transplantation (L-GrAFT) scores), clinically relevant non-anastomotic biliary complications, comprehensive surgical complication index, Clavien-Dindo complication grade, and graft/patient survival. Clinical outcome data up to 5 years post-transplant will be collected if required, at 12 months post transplant Mitochondrial function in DCD livers measured using changes in mitochondrial complex I enzyme activity in liver tissue samples at 30 minutes and 4 hours after initiation of normothermic machine perfusion (NMP) Quality and suitability for transplantation of DCD livers measured using associations between biomarkers of liver damage and function collected from liver tissue, perfusate, and recipient blood and post-transplant clinical outcomes, with samples collected at before NMP, at 30 minutes and 2 hours during NMP, and at 2 hours post-reperfusion in the recipient
Key secondary outcome measure(s)	Oxidative damage to mitochondrial DNA (mtDNA), genomic DNA (gDNA), and cardiolipin in liver tissue, measured using quantitative assays of oxidised mtDNA, gDNA, and cardiolipin, at before NMP, 30 min and 2 h after initiating NMP, and 2 h after reperfusion in the recipient Metabolic and transcriptional profiles of liver and bile duct tissue, measured using targeted metabolomics of polar and non‑polar metabolites and bulk RNA sequencing at before NMP, 30 min and 2 h after initiating NMP, and 2 h after reperfusion in the recipient Immune activation and cell‑free nucleic acid release during NMP, measured using quantification of immune cell subsets and inflammatory cytokines in perfusate, single‑cell RNA sequencing of liver tissue, and measurement of mtDNA and cell‑free DNA (cfDNA) in perfusate, at before NMP, 30 min and 2 h after initiating NMP, and 2 h after reperfusion in the recipient Liver injury, function, and bile composition during NMP, measured using data collected on sequential perfusate biochemical markers (AST, ALT, bilirubin, alkaline phosphatase, LDH, lactate), bile production and bile pH, bicarbonate and glucose concentrations, liver and bile duct histology, and perfusate proteomics, at one time point Post‑transplant ischaemia‑reperfusion injury and graft outcomes, measured using data collected on surrogate clinical endpoints including reperfusion syndrome, early allograft dysfunction assessed by MEAF and L‑GrAFT scores, clinically relevant non‑anastomotic biliary complications, Comprehensive Complication Index, Clavien–Dindo complication grade, and 6-month graft and patient survival, at one time point Associations between biomarkers of liver damage and function during NMP and post‑transplant clinical outcomes measured using statistical association analyses between biomarker data and clinical endpoints at one time point Use of retrieved livers by preservation strategy measured using the proportion of livers retrieved and subsequently transplanted for each preservation strategy at one time point
Completion date	31/12/2026

Eligibility

Participant type(s)
Age group	Mixed
Lower age limit	18 Years
Upper age limit	99 Years
Sex	All
Target sample size at registration	36
Key inclusion criteria	Donor inclusion criteria: 1. DCD category III donors considered for abdominal organs-only retrieval 2. Donor age ≥18 years 3. Retrieval procedure allocated to the recruiting site’s NORS team 4. Donor liver accepted for a patient on the recruiting site’s transplant waiting list via the standard offering process 5. Donor BMI <35kg/m2 6. Predicted cold ischaemic time <8 hours 7. Donor family has given consent to use donated liver for research Recipient inclusion criteria: 1. Recipients 18 years of age or older 2. Listed on an elective transplant waiting list 3. Suitable to receive a DCD graft based on the liver listing MDT 4. Willing and able to consent for the study participation
Key exclusion criteria	Donor exclusion criteria (at the time of randomisation): 1. Donor is HIV, hepatitis B (HBV HbsAg) or hepatitis C (HCV RNA) positive 2. Any medical condition that, in the opinion of the principal investigator, would interfere with safe completion of the trial Donor exclusion criteria (at the time of retrieval): 1. Liver weight >2.5 kg 2. Macroscopic evidence of advanced fibrosis 3. Functional donor warm ischaemia (defined as a period between the systolic blood pressure <50mmHg and aortic cold flush) >30 minutes 4. Any other clinical issue that in the opinion of the surgical team constitutes a contraindication to proceed with transplantation Recipient exclusion criteria: 1. High-risk surgical candidates (e.g. presence of extensive portomesenteric thrombosis, previous complex upper abdominal surgery) 2. Patients undergoing liver re-transplantation or multi-organ transplantation 3. Patients receiving super-urgent transplantation for acute and acute-on-chronic liver failure
Date of first enrolment	25/03/2025
Date of final enrolment	31/05/2026

Locations

Countries of recruitment

United Kingdom
England

Study participating centres

Kings College Hospital

Denmark Hill
London
SE5 9RS
England

Cambridge University Hospitals NHS Foundation Trust

Addenbrookes Hospital
Cambridge
CB2 0AU
England

Royal Free London NHS Foundation Trust

Royal Free Hospital
Pond Street
London
NW3 2QG
England

University Hospitals Birmingham NHS Ft

Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
England

Results and Publications

Individual participant data (IPD) Intention to share	No

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol file	version 4	21/07/2025	07/04/2026	No	No

Additional files

49329_Protocol_V4_21July2025.pdf: Protocol file

Editorial Notes

07/05/2026: Internal review.
21/04/2026: Study's existence confirmed by Health Research Authority (HRA) (UK).