Liver Transplant DisorderNCT07315204
Viability Assessment Using FMN Measured in Perfusate and Bile During Normothermic Machine Perfusion
An observational study of Liver Transplant Disorder, run by The Cleveland Clinic at 1 site in United States.
Trial summary
Discarded perfusate samples will be collected from donors after circulatory death (DCD) or donors after brain death (DBD) organs during the machine perfusion period prior to transplantation by the study team. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Transplant Disorder
- How many people
- 850 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Mar 2026to 31 Dec 2028
- Phase
- Observational
- 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
Study population: Recipients of deceased-donor liver transplant (DCD and DBD) will be recruited from outpatient clinics and inpatient services at the Cleveland Clinic Foundation Main Campus in the department of liver transplant. Patients will undergo their complete liver transplant work-up as directed by the multi-disciplinary selection committee and under the national direction of the United Network for Organ Sharing (UNOS). After completing their work-up, patients are discussed at the Liver Transplant Selection Committee, who must come to a consensus agreement regarding a candidate's eligibility prior to transplant. Each patient undergoing primary liver transplantation alone for end stage liver disease and/or liver tumor is eligible once approved by the committee, because this is an observational study comparing perfusion samples with standard-of-care clinical outcomes. Participating centers in this study will follow the standard procedures of their respective institutions.
Who may be able to join
- Age >18 years
- Any graft type (DBD or DCD)
- Any underlying recipient disease (i.e., end stage, liver tumour)
- Any other donor risk factors and static cold storage time prior to NMP accepted by the participating center for transplantation in context of OrganOx metra use
- Patients undergoing primary deceased donor liver transplantation where back-to-base NMP is used (OrganOx metra) from July 15, 2025 to December 31, 2027. (CCF only)
- Patients who have undergone deceased donor liver transplantation where back-to-base NMP was used (OrganOx metra) from October 22, 2022 to July 14, 2025. (CCF only)
Who cannot join
- Patients receiving a liver graft that is not perfused with OrganOx metra
- Pediatric recipients (<18years)
- Patients listed for super urgent liver transplantation due to acute liver failure
- Patients receiving combined organ transplant (heart+liver, lung+liver, liver+kidney, liver+intestine)
- Patients receiving living donor liver transplant or a split (or reduced) liver transplantation or a domino graft.
- Re-transplantations
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Andrea Schlegel, MD, MBA, 216-339-0741, schlega4@ccf.org
Mary Bilancini, MS, 216-444-8983, bilancm@ccf.org
About this study
Official title: Viability Assessment Using Flavin Mononucleotide (FMN) Measured in Perfusate and Bile During Normothermic Machine Perfusion: an International, Multi-center Validation Study
Discarded perfusate samples will be collected from donors after circulatory death (DCD) or donors after brain death (DBD) organs during the machine perfusion period prior to transplantation by the study team. FMN will be measured as is standard of care for all machine perfusion liver transplant cases at Cleveland Clinic.
Participating centers will be provided with sample collection and shipping instructions to ensure sample preservation in accordance with IATA guidelines. Samples from outside sites will not be stored for future research and will be discarded once analysis is completed.
After the collection of the samples from machine perfusion, the transplant procedure will continue according to standard process.
Read the detailed description
Real-time identification of graft viability is critical to safe expansion of the donor pool. Different strategies for viability testing in Normothermic Machine Perfusion (NMP) have been described by groups from the United Kingdom, The Netherlands, Austria, United States and Switzerland. In general, strategies in NMP utilize clinical observations, perfusion conditions, plus perfusate and bile analyses including lactate clearance, pH, glucose utilization/reuptake and more. At present there is no consensus for viability parameters or certain thresholds, though lactate clearance and clinical observation seem to be the most widely used criteria at present time.
Viability assessment has been reported for Hypothermic oxygenated perfusion (HOPE)-treated grafts, mostly centered around Flavin Mononucleotide (FMN), a marker of mitochondrial injury originating from mitochondrial Complex 1. FMN was shown to be released into perfusate at reoxygenation of previously ischemic tissues and correlating well with posttransplant complications and predicting graft loss beyond certain perfusate thresholds obtained during HOPE. This has led to improvements in graft loss and reduction of clinically relevant non-anastomotic strictures (NAS) with HOPE despite the use of extended criteria DCD livers (any donor age up to 100 years, old donors, >30min functional donor warm ischemia time (fDWIT), up to 8hrs static cold storage before HOPE, macrosteatosis) in Europe. Dr. Schlegel's group has recently validated prior thresholds center wide and internationally repeatedly showing the correlation between perfusate FMN and clinically relevant post-LT outcomes.
The investigators have investigated the utility of perfusate FMN obtained during NMP using the OrganOx metra device predicting graft loss and complications. Specifically, the investigators find that FMN predicts NAS, overall complications and graft loss after transplant. Perhaps most impressively, the investigators find that quantitative measurement of FMN can predict not only binary complications, but also severity of such complications in perfused grafts. The investigators further find that typical parameters such as lactate, glucose and bile chemistry are poorly correlated with post-transplant outcomes.
Finally, the investigators have validated FMN measured in bile as an add on identifying biliary injury in both a binary and a quantitative sense, specifically predicting biliary complications with different clinical severity and need for interventions.
This is a multicenter observational validation study. It is estimated 850 that patients will be needed across 10-15 study sites to confirm FMN as a viability marker during NMP. Around 250 patients will be enrolled from Cleveland Clinic, both retrospectively and prospectively, from October 22, 2022 - December 31, 2027.
- The primary aim of this study is to confirm and validate the ability of Flavin Mononucleotide (FMN) as a marker of future graft viability. The investigators aim in total for 10 to 15 participating centers, both in the US and UK, utilizing back-to-base normothermic machine perfusion with the OrganOx metra device.
Primary Endpoint: Graft functionality up to 1-year post-transplant, as measured by perfusate FMN, bile FMN and perfusate + bile FMN correlation with graft viability (Primary Non-function (PNF), non-anastomotic stricture (NAS), other related graft loss - death censored).
Secondary Endpoints:
- Clinically significant non-anastomotic strictures (NAS requiring intervention).
- All biliary complications, including AS, NAS, bile leaks
- Clinically significant NAS leading to graft loss
- Number of interventions required per NAS
- Complications according to Clavien-Dindo grading and comprehensive Complications Index (CCI)
- Primary nonfunction (PNF), early allograft dysfunction (EAD)
- Hepatic artery thrombosis (HAT) and other vascular complications
- Acute kidney injury (AKI), renal replacement therapy (RRT)
- Acute cellular rejection, number of biopsies, number of rejection episodes and severity
- Graft loss, death censored graft loss, recipient death, times and causes
- Conditions
- Liver Transplant Disorder
- Keywords
- normothermic machine perfusion, flavin mononucleotide, graft viability, liver transplant, OrganOx metra
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Recipients who receive deceased-donor liver transplant using machine perfusion with OrganOx metra | Normothermic perfusion using OrganOx metra. Can be from DBD or DCD donor. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Graft functionality as measured by FMN correlation with graft viability at 1 year post transplant
Graft functionality measured by perfusate FMN, bile FMN, and perfusate + bile FMN. Graft viability measured by primary non-function (PNF). Non-anastomotic stricture (NAS), other graft related loss - death censored.
Measured: 1 year post transplant
Secondary outcomes (10)
Clinically significant non-anastomotic strictures
Number of non-anastomotic strictures requiring intervention
Measured: within 1 year post-transplant
Number/percentage of biliary complications
Biliary complications include anastomotic stricture (AS), NAS, bile leaks, as seen on imaging, ERCP/MRCP.
Measured: within 1 year post-transplant
Clinically significant NAS leading to graft loss
Number of non-anastomotic strictures that result in graft failure
Measured: within 1 year post-transplant
Number of interventions required per NAS
Measured: within 1 year post-transplant
Number of complications according to Clavien-Dindo grading and comprehensive Complications Index (CCI)
Measured: within 1 year post-transplant
Percentage of patients with primary nonfunction (PNF) and early allograft dysfunction (EAD)
EAD defined using Olthoff Criteria. PNF defined as non-functioning liver with patent vessels with 7 days after liver transplant.
Measured: within 7-10 days post-transplant
Percentage of subjects with hepatic artery thrombosis (HAT) and other vascular complications
Subjects will be followed from time of surgery for at least one year post-transplant per institute standard. Complications, surgeries, etc will be collected and analyzed.
Measured: within 1 year post-transplant
Number/Percentage of subjects with acute kidney injury (AKI), renal replacement therapy (RRT)
Measured: within 1 year post-transplant
Number/percentage of subjects with acute cellular rejection (ACR)
For subjects with ACR, the number of biopsies, number of rejection episodes, and the severity will be reported
Measured: within 1 year post-transplant
Graft loss
Number of grafts lost. Death censored graft loss, number of patient deaths, times, and causes of death.
Measured: within 1 year post-transplant.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2026
- Study start13 Mar 2026
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver Transplant DisorderStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 850 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrea Schlegel, The Cleveland Clinic
- Investigators
- Andrea Schlegel, MD, MBA, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07315204
- Sponsor's protocol ID
- 25-839
- Status last verified
- Mar 2026
- First submitted
- 18 Dec 2025
- Last updated
- 4 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- 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 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Viability Assessment Using Flavin Mononucleotide (FMN) Measured in Perfusate and Bile During Normothermic Machine Perfusion: an International, Multi-center Validation Study
- ClinicalTrials.gov ID
- NCT07315204
- Acronym / sponsor ID
- 25-839
- Conditions
- Liver Transplant Disorder
- Keywords
- normothermic machine perfusion, flavin mononucleotide, graft viability, liver transplant, OrganOx metra
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 850 participants (estimated)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Study start
- 13 Mar 2026 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 2 Jan 2026 (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.
Discarded perfusate samples will be collected from donors after circulatory death (DCD) or donors after brain death (DBD) organs during the machine perfusion period prior to transplantation by the study team. FMN will be measured as is standard of care for all machine perfusion liver transplant cases at Cleveland Clinic.
Participating centers will be provided with sample collection and shipping instructions to ensure sample preservation in accordance with IATA guidelines. Samples from outside sites will not be stored for future research and will be discarded once analysis is completed.
After the collection of the samples from machine perfusion, the transplant procedure will continue according to standard process.
Detailed description
Real-time identification of graft viability is critical to safe expansion of the donor pool. Different strategies for viability testing in Normothermic Machine Perfusion (NMP) have been described by groups from the United Kingdom, The Netherlands, Austria, United States and Switzerland. In general, strategies in NMP utilize clinical observations, perfusion conditions, plus perfusate and bile analyses including lactate clearance, pH, glucose utilization/reuptake and more. At present there is no consensus for viability parameters or certain thresholds, though lactate clearance and clinical observation seem to be the most widely used criteria at present time.
Viability assessment has been reported for Hypothermic oxygenated perfusion (HOPE)-treated grafts, mostly centered around Flavin Mononucleotide (FMN), a marker of mitochondrial injury originating from mitochondrial Complex 1. FMN was shown to be released into perfusate at reoxygenation of previously ischemic tissues and correlating well with posttransplant complications and predicting graft loss beyond certain perfusate thresholds obtained during HOPE. This has led to improvements in graft loss and reduction of clinically relevant non-anastomotic strictures (NAS) with HOPE despite the use of extended criteria DCD livers (any donor age up to 100 years, old donors, >30min functional donor warm ischemia time (fDWIT), up to 8hrs static cold storage before HOPE, macrosteatosis) in Europe. Dr. Schlegel's group has recently validated prior thresholds center wide and internationally repeatedly showing the correlation between perfusate FMN and clinically relevant post-LT outcomes.
The investigators have investigated the utility of perfusate FMN obtained during NMP using the OrganOx metra device predicting graft loss and complications. Specifically, the investigators find that FMN predicts NAS, overall complications and graft loss after transplant. Perhaps most impressively, the investigators find that quantitative measurement of FMN can predict not only binary complications, but also severity of such complications in perfused grafts. The investigators further find that typical parameters such as lactate, glucose and bile chemistry are poorly correlated with post-transplant outcomes.
Finally, the investigators have validated FMN measured in bile as an add on identifying biliary injury in both a binary and a quantitative sense, specifically predicting biliary complications with different clinical severity and need for interventions.
This is a multicenter observational validation study. It is estimated 850 that patients will be needed across 10-15 study sites to confirm FMN as a viability marker during NMP. Around 250 patients will be enrolled from Cleveland Clinic, both retrospectively and prospectively, from October 22, 2022 - December 31, 2027.
- The primary aim of this study is to confirm and validate the ability of Flavin Mononucleotide (FMN) as a marker of future graft viability. The investigators aim in total for 10 to 15 participating centers, both in the US and UK, utilizing back-to-base normothermic machine perfusion with the OrganOx metra device.
Primary Endpoint: Graft functionality up to 1-year post-transplant, as measured by perfusate FMN, bile FMN and perfusate + bile FMN correlation with graft viability (Primary Non-function (PNF), non-anastomotic stricture (NAS), other related graft loss - death censored).
Secondary Endpoints:
- Clinically significant non-anastomotic strictures (NAS requiring intervention).
- All biliary complications, including AS, NAS, bile leaks
- Clinically significant NAS leading to graft loss
- Number of interventions required per NAS
- Complications according to Clavien-Dindo grading and comprehensive Complications Index (CCI)
- Primary nonfunction (PNF), early allograft dysfunction (EAD)
- Hepatic artery thrombosis (HAT) and other vascular complications
- Acute kidney injury (AKI), renal replacement therapy (RRT)
- Acute cellular rejection, number of biopsies, number of rejection episodes and severity
- Graft loss, death censored graft loss, recipient death, times and causes
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Recipients who receive deceased-donor liver transplant using machine perfusion with OrganOx metra | – | –Normothermic perfusion using OrganOx metra. Can be from DBD or DCD donor. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Recipients of deceased-donor liver transplant (DCD and DBD) will be recruited from outpatient clinics and inpatient services at the Cleveland Clinic Foundation Main Campus in the department of liver transplant. Patients will undergo their complete liver transplant work-up as directed by the multi-disciplinary selection committee and under the national direction of the United Network for Organ Sharing (UNOS). After completing their work-up, patients are discussed at the Liver Transplant Selection Committee, who must come to a consensus agreement regarding a candidate's eligibility prior to transplant. Each patient undergoing primary liver transplantation alone for end stage liver disease and/or liver tumor is eligible once approved by the committee, because this is an observational study comparing perfusion samples with standard-of-care clinical outcomes. Participating centers in this study will follow the standard procedures of their respective institutions.
Key inclusion criteria (6 listed)
- Age >18 years
- Any graft type (DBD or DCD)
- Any underlying recipient disease (i.e., end stage, liver tumour)
- Any other donor risk factors and static cold storage time prior to NMP accepted by the participating center for transplantation in context of OrganOx metra use
- Patients undergoing primary deceased donor liver transplantation where back-to-base NMP is used (OrganOx metra) from July 15, 2025 to December 31, 2027. (CCF only)
Key exclusion criteria (6 listed)
- Patients receiving a liver graft that is not perfused with OrganOx metra
- Pediatric recipients (<18years)
- Patients listed for super urgent liver transplantation due to acute liver failure
- Patients receiving combined organ transplant (heart+liver, lung+liver, liver+kidney, liver+intestine)
- Patients receiving living donor liver transplant or a split (or reduced) liver transplantation or a domino graft.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Graft functionality as measured by FMN correlation with graft viability at 1 year post transplant
Time frame: 1 year post transplant
Graft functionality measured by perfusate FMN, bile FMN, and perfusate + bile FMN. Graft viability measured by primary non-function (PNF). Non-anastomotic stricture (NAS), other graft related loss - death censored.
10 secondary outcomes
Clinically significant non-anastomotic strictures
Time frame: within 1 year post-transplant
Number/percentage of biliary complications
Time frame: within 1 year post-transplant
Clinically significant NAS leading to graft loss
Time frame: within 1 year post-transplant
Number of interventions required per NAS
Time frame: within 1 year post-transplant
Number of complications according to Clavien-Dindo grading and comprehensive Complications Index (CCI)
Time frame: within 1 year post-transplant
Percentage of patients with primary nonfunction (PNF) and early allograft dysfunction (EAD)
Time frame: within 7-10 days post-transplant
Percentage of subjects with hepatic artery thrombosis (HAT) and other vascular complications
Time frame: within 1 year post-transplant
Number/Percentage of subjects with acute kidney injury (AKI), renal replacement therapy (RRT)
Time frame: within 1 year post-transplant
Number/percentage of subjects with acute cellular rejection (ACR)
Time frame: within 1 year post-transplant
Graft loss
Time frame: within 1 year post-transplant.
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 4 Jun 2026.
- 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.
Andrea Schlegel, MD, MBA principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Liver Transplant Disorder, run by The Cleveland Clinic at 1 site in United States.
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 6 inclusion and 6 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 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 Mary Bilancini, MS (216-444-8983, bilancm@ccf.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Graft functionality as measured by FMN correlation with graft viability at 1 year post transplant (time frame: 1 year post transplant). 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 4 Jun 2026.