Liver TransplantationiMapsNCT06371924
Immunometabolism of Machine Perfusion Strategies
A study testing Machine Perfusion in people with Liver Transplantation, run by King's College Hospital NHS Trust at 2 sites in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Transplantation
- What is being tested?
- Machine Perfusion
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 17 Feb 2025to 31 May 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- DCD category III donors considered for abdominal organs-only retrieval.
- Donor age ≥18 years.
- Retrieval procedure allocated to KCH or UHB NORS teams.
- Donor liver accepted for a patient at KCH or UHB transplant waiting list via the standard offering process.
- Functional donor warm ischaemia (defined as a period between the systolic blood pressure <50mmHg and aortic cold flush) ≤30 minutes.
- Donor BMI <35kg/m2.
Show all 14Show fewer
- Predicted cold ischaemic time <8 hours.
- Donor family has given consent to use donated liver for research.
- Transplant recipient inclusion criteria
- Recipients 18 years of age or older.
- Listed on an elective transplant waiting list.
- First liver transplantation.
- Suitable to receive a DCD graft based on the liver listing MDT.
- Willingness to consent for the study participation.
Who cannot join
- Donor is HIV, hepatitis B (HBV HbsAg) or hepatitis C (HCV RNA) positive. HBV anti-Hbc positive donors are acceptable.
- Macroscopic evidence of fibrosis.
- Liver weight >2.5 kg.
- Retrieval of cardiothoracic organs intended for transplantation.
- Any medical condition that, in the opinion of the principal investigator, would interfere with safe completion of the trial.
- Transplant recipient exclusion criteria
Show all 9Show fewer
- High-risk surgical candidates (i.e. presence of extensive portomesenteric thrombosis, previous complex upper abdominal surgery).
- Patients receiving super-urgent transplantation for acute and acute-on-chronic liver failure.
- Patients unable to give full informed consent.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom2 sites, 2 recruiting
- Recruiting
University Hospitals Birmingham NHS Foundation Trust
Birmingham, B15 2GW
Bobby Dasari, 44121 627 2000, Bobby.Dasari@uhb.nhs.uk
- Recruiting
Royal Free London NHS Foundation Trust
London, NW3 2QG
Carlo Ceresa, 4420 7794 0500, carlo.ceresa1@nhs.net
About this study
Official title: Mechanistic Evaluation of Machine Perfusion Strategies in Donation After Circulatory Death Liver Transplantation
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 that can also improve the quality of the DCD livers, involve using machines to pump fluids through the livers ('machine perfusion' or MP).
Read more
There are three MP methods 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 the doctors do not understand well the mechanisms through which MP improves the quality of the DCD livers.
The iInvestigators plan 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.
Read the detailed description
Liver transplant numbers do not meet the existing needs, thousands of patients remain on transplant waiting lists worldwide and many die while awaiting a life-saving organ. A key contributor to organ shortage is the discarding of viable organs coming from donors considered high-risk, for fear that they might malfunction after transplantation as a result of a phenomenon called ischaemia reperfusion injury (IRI). Most of the discarded livers are those donated after circulatory death (DCD), only 27% of which are currently utilised in the UK. The quality of DCD organs can be improved by replacing the icebox (static cold storage or SCS), which remains the main approach to preserve the livers after having been retrieved, by strategies that perfuse the livers in a machine (machine perfusion or MP). There are currently 3 MP strategies employed in the clinic: normothermic regional perfusion (NRP) is used in the donors by perfusing the liver with the donor's blood at 37 degrees Celsius, and normothermic (NMP) or hypothermic (HOPE) perfusion are used in the procured livers out of the body (using warm or cold perfusion fluids, respectively). To date, no controlled objective comparisons of these different MP strategies have been undertaken and doctors do not have a good understanding of their mechanisms of action. The investigators hypothesise that the benefits of MP will depend on the capacity of these strategies to improve the damage to the liver cell mitochondria, which constitutes the first event that elicits IRI at the time of transplantation. To determine this, the investigators propose to conduct a randomised clinical trial in which 36 DCD human livers will be allocated to 1 of 3 treatment arms: i) SCS; ii) NRP; and iii) HOPE. This will be followed by a period of time in NMP in order to study the IRI response and determine if the quality of the livers is good enough to proceed to transplantation. Following transplantation, patients will be followed for up to 12 months.
Our proposal will include three key objectives:
- To investigate the role of mitochondrial damage in the IRI that takes place when DCD livers are transplanted.
- To determine the mechanisms through which the different MP strategies influence IRI in DCD liver transplantation.
- To develop markers to assess the quality of the livers while they are being perfused using NMP before being transplanted into patients.
Our study will allow us to decipher the mechanisms of liver IRI in humans in a much better way than what has been achieved to date. Furthermore, it will provide guidelines as to the best way of employing the MP technologies and may result in the identification of new treatments. Ultimately, our proposal will serve to improve the quality of DCD livers and increase the number of patients who can safely receive a liver transplant.
- Conditions
- Liver Transplantation
- Being tested
- Machine Perfusion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Machine PerfusionDevice
The quality of DCD organs can be improved by replacing the icebox (static cold storage or SCS), which remains the main approach to preserve the livers after having been retrieved, by strategies that perfuse the livers in a machine (machine perfusion or MP). There are currently 3 MP strategies employed in the clinic: normothermic regional perfusion (NRP) is used in the donors by perfusing the liver with the donor's blood at 37 degrees Celsius, and normothermic (NMP) or hypothermic (HOPE) perfusion are used in the procured livers out of the body (using warm or cold perfusion fluids, respectively). To date, no controlled objective comparisons of these different MP strategies have been undertaken and the doctors do not have a good understanding of their mechanisms of action.
| Study group | Role | What they receive |
|---|---|---|
| Static Cold Storage | Active comparator | The donor liver will be flushed in situ with 4C UW preservation solution (or HTK) through the aorta and portal vein, retrieved, and transported to the transplant centre in an icebox. Receives: Device: Machine Perfusion |
| Normothermic Regional Perfusion | Active comparator | 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 37C for 2h (while monitoring pump flow, venous O2 saturation, lactate and ALT), followed by in-situ flush with 4C preservation solution as in SCS arm. Receives: Device: Machine Perfusion |
| Hypothermic oxygenated perfusion | Active comparator | The liver will be retrieved and preserved as in 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 2h. Receives: Device: Machine Perfusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the effect of different preservation strategies on the development of mitochondrial damage following reperfusion during NMP.
changes in mitochondrial complex I enzyme activity in liver tissue samples obtained 30 minutes and 4 hours after initiating NMP, as assessed by an established spectrophotometric assay (values will be reported as a ratio to citrate synthase)
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2024
- Study start17 Feb 2025
- Primary completion31 May 2026 (estimated)
- Study completion31 May 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver TransplantationStudies of the same condition, open and under way.
- More trials run by King's College Hospital NHS TrustThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The investigators propose to conduct a randomised clinical trial in which 36 DCD human livers will be allocated to 1 of 3 treatment arms: i) SCS; ii)NRP; and iii) HOPE. This will be followed by a period of time in NMP in order to study the IRI response and determine if the quality of the livers is good enough to proceed to transplantation. This study will allow the doctors to decipher the mechanisms of liver IRI in humans in a much better way than what has been achieved to date.
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- King's College Hospital NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- King's College London
- Responsible party
- Sponsor
- Investigators
- Alberto Sanchez-Fueyo, Principal investigator, King's College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06371924
- Sponsor's protocol ID
- KCH23-156
- Acronym
- iMaps
- Status last verified
- Jul 2025
- First submitted
- 13 Feb 2024
- Last updated
- 13 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanistic Evaluation of Machine Perfusion Strategies in Donation After Circulatory Death Liver Transplantation
- ClinicalTrials.gov ID
- NCT06371924
- Acronym / sponsor ID
- iMaps / KCH23-156
- Conditions
- Liver Transplantation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- King's College Hospital NHS TrustUniversity, hospital or other
- Collaborators
- King's College London
- Study start
- 17 Feb 2025 (actual)
- Primary completion
- 31 May 2026 (estimated)
- Study completion
- 31 May 2026 (estimated)
- First posted
- 17 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 that can also improve the quality of the DCD livers, involve using machines to pump fluids through the livers ('machine perfusion' or MP).
There are three MP methods 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 the doctors do not understand well the mechanisms through which MP improves the quality of the DCD livers.
The iInvestigators plan 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.
Detailed description
Liver transplant numbers do not meet the existing needs, thousands of patients remain on transplant waiting lists worldwide and many die while awaiting a life-saving organ. A key contributor to organ shortage is the discarding of viable organs coming from donors considered high-risk, for fear that they might malfunction after transplantation as a result of a phenomenon called ischaemia reperfusion injury (IRI). Most of the discarded livers are those donated after circulatory death (DCD), only 27% of which are currently utilised in the UK. The quality of DCD organs can be improved by replacing the icebox (static cold storage or SCS), which remains the main approach to preserve the livers after having been retrieved, by strategies that perfuse the livers in a machine (machine perfusion or MP). There are currently 3 MP strategies employed in the clinic: normothermic regional perfusion (NRP) is used in the donors by perfusing the liver with the donor's blood at 37 degrees Celsius, and normothermic (NMP) or hypothermic (HOPE) perfusion are used in the procured livers out of the body (using warm or cold perfusion fluids, respectively). To date, no controlled objective comparisons of these different MP strategies have been undertaken and doctors do not have a good understanding of their mechanisms of action. The investigators hypothesise that the benefits of MP will depend on the capacity of these strategies to improve the damage to the liver cell mitochondria, which constitutes the first event that elicits IRI at the time of transplantation. To determine this, the investigators propose to conduct a randomised clinical trial in which 36 DCD human livers will be allocated to 1 of 3 treatment arms: i) SCS; ii) NRP; and iii) HOPE. This will be followed by a period of time in NMP in order to study the IRI response and determine if the quality of the livers is good enough to proceed to transplantation. Following transplantation, patients will be followed for up to 12 months.
Our proposal will include three key objectives:
- To investigate the role of mitochondrial damage in the IRI that takes place when DCD livers are transplanted.
- To determine the mechanisms through which the different MP strategies influence IRI in DCD liver transplantation.
- To develop markers to assess the quality of the livers while they are being perfused using NMP before being transplanted into patients.
Our study will allow us to decipher the mechanisms of liver IRI in humans in a much better way than what has been achieved to date. Furthermore, it will provide guidelines as to the best way of employing the MP technologies and may result in the identification of new treatments. Ultimately, our proposal will serve to improve the quality of DCD livers and increase the number of patients who can safely receive a liver transplant.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- The investigators propose to conduct a randomised clinical trial in which 36 DCD human livers will be allocated to 1 of 3 treatment arms: i) SCS; ii)NRP; and iii) HOPE. This will be followed by a period of time in NMP in order to study the IRI response and determine if the quality of the livers is good enough to proceed to transplantation. This study will allow the doctors to decipher the mechanisms of liver IRI in humans in a much better way than what has been achieved to date.
| Arm | Type | Receives |
|---|---|---|
| Static Cold Storage | Active comparator | Device: Machine PerfusionThe donor liver will be flushed in situ with 4C UW preservation solution (or HTK) through the aorta and portal vein, retrieved, and transported to the transplant centre in an icebox. |
| Normothermic Regional Perfusion | Active comparator | Device: Machine PerfusionThe 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 37C for 2h (while monitoring pump flow, venous O2 saturation, lactate and ALT), followed by in-situ flush with 4C preservation solution as in SCS arm. |
| Hypothermic oxygenated perfusion | Active comparator | Device: Machine PerfusionThe liver will be retrieved and preserved as in 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 2h. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- DCD category III donors considered for abdominal organs-only retrieval.
- Donor age ≥18 years.
- Retrieval procedure allocated to KCH or UHB NORS teams.
- Donor liver accepted for a patient at KCH or UHB transplant waiting list via the standard offering process.
- Functional donor warm ischaemia (defined as a period between the systolic blood pressure <50mmHg and aortic cold flush) ≤30 minutes.
Key exclusion criteria (9 listed)
- Donor is HIV, hepatitis B (HBV HbsAg) or hepatitis C (HCV RNA) positive. HBV anti-Hbc positive donors are acceptable.
- Macroscopic evidence of fibrosis.
- Liver weight >2.5 kg.
- Retrieval of cardiothoracic organs intended for transplantation.
- Any medical condition that, in the opinion of the principal investigator, would interfere with safe completion of the trial.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Machine PerfusionThe quality of DCD organs can be improved by replacing the icebox (static cold storage or SCS), which remains the main approach to preserve the livers after having been retrieved, by strategies that perfuse the livers in a machine (machine perfusion or MP). There are currently 3 MP strategies employed in the clinic: normothermic regional perfusion (NRP) is used in the donors by perfusing the liver with the donor's blood at 37 degrees Celsius, and normothermic (NMP) or hypothermic (HOPE) perfusion are used in the procured livers out of the body (using warm or cold perfusion fluids, respectively). To date, no controlled objective comparisons of these different MP strategies have been undertaken and the doctors do not have a good understanding of their mechanisms of action. | Device | Hypothermic oxygenated perfusion, Normothermic Regional Perfusion, Static Cold Storage |
Primary outcome
To determine the effect of different preservation strategies on the development of mitochondrial damage following reperfusion during NMP.
Time frame: 2 years
changes in mitochondrial complex I enzyme activity in liver tissue samples obtained 30 minutes and 4 hours after initiating NMP, as assessed by an established spectrophotometric assay (values will be reported as a ratio to citrate synthase)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Alberto Sanchez-Fueyo principal investigator
King's College London
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Machine Perfusion in people with Liver Transplantation, run by King's College Hospital NHS Trust at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alberto Sanchez-Fueyo (02078485883, sanchez_fueyo@kcl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the effect of different preservation strategies on the development of mitochondrial damage following reperfusion during NMP. (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2025.