Ignite Creation Date:
2026-03-26 @ 3:16 PM
Ignite Modification Date:
2026-03-30 @ 1:04 AM
Study NCT ID:
NCT07315204
Status:
RECRUITING
Last Update Posted:
2026-01-07
First Post:
2025-12-18
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Viability Assessment Using FMN Measured in Perfusate and Bile During Normothermic Machine Perfusion
Sponsor:
The Cleveland Clinic
Organization:
Study Overview
Official Title:
Viability Assessment Using Flavin Mononucleotide (FMN) Measured in Perfusate and Bile During Normothermic Machine Perfusion: an International, Multi-center Validation Study
Status:
RECRUITING
Status Verified Date:
2026-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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. 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.
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
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 Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: