Ignite Creation Date:
2024-05-06 @ 5:29 PM
Last Modification Date:
2024-10-26 @ 2:30 PM
Study NCT ID:
NCT05327478
Status:
RECRUITING
Last Update Posted:
2022-04-14
First Post:
2022-02-24
Brief Title:
NRP vs DHOPE vs COR-NMP in ECD-DCD Donation
Sponsor:
Erasmus Medical Center
Organization:
Erasmus Medical Center
Study Overview
Official Title:
Direct Comparison of NRP With DHOPE and COR-NMP to Maximize the Use of ECD After DCD Donation in the Netherlands
Status:
RECRUITING
Status Verified Date:
2022-04
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:
There is still a discrepancy between the number of liver transplant candidates and the availability of liver grafts resulting in waiting list mortality To increase the supply of suitable liver grafts extended-donor criteria allografts can be used However in the case of donation after cardiac death this is not without a risk Donor after cardiac death DCD grafts have increased risk of primary non function and biliary complications resulting in either retransplantation patient morbidity or patient death Due to uncertainty of their quality DCD grafts can be discarded However normothermic machine perfusion NRP has the potential to overcome these disadvantages of DCD liver grafts In DCD livers the physiological abdominal circulation is simulated with in vivo normothermic oxygenated perfusion during the first two hours after cardiac death With this perfusion technique early ischemia can be reversed surgical damage due to a hasty procedure can be prevented and organs can be tested on viability In many countries NRP is obligatory however this is not the current golden standard in the Netherlands The primary objective of this study is the utilization of livers after NRP Secondary study parameters are reasons for graft discard or rejection at proposal patient- and graft survival biliary complications cost assessment of NRP and outcomes of kidney and pancreas transplants This multicenter observational study will be performed on adult liver transplant recipients who have been allocated a DCD liver graft Maastricht type III and V of a donor above fifty years old According to current national procurement protocol grafts procured in region west will be retrieved with NRP followed by dual hypothermic oxygenated perfusion DHOPE Grafts retrieved in region EastNorth will be retrieved using standard rapid retrieval followed by DHOPE if the donor is aged 50-60 Grafts from donors aged above 60 will undergo controlled oxygenated rewarming normothermic machine perfusion COR-NMP after DHOPE
Detailed Description:
The persistent discrepancy between the number of patients awaiting liver transplant and the availability of liver grafts In the Netherlands still 1 in 5 either dies on the waiting list or is removed from the waiting list due to deterioration of the disease To increase the supply of suitable liver grafts extended-donor criteria allografts can be used Extended criteria donors ECD include older donors donors with fatty livers donors with high transaminase levels and donor after circulatory death DCD However because of an inevitable longer period of warm ischemia DCD livers have increased risk of primary non function and biliary complications resulting in either patient morbidity re-transplantation or patient death Due to uncertainty of the effect of the longer ischemia time on their quality DCD grafts can be accepted with reluctance or even discarded
The persistent organ shortage has forced transplant programs to explore options to expand the organ supply Parallel to this interest in use of extended criteria donors ECD livers drove an evolution in current technique to retrieve preserve and improve livers before transplantation Before the era of perfusion the organs were retrieved by using standard rapid retrieval SRR and preserved by static cold storage SCS In 1930 researchers have explored machine perfusion as a technique to preserve organs but nowadays this technique has many more potentials including testing and improving Currently there is a wide diversity in different perfusion techniques varying from in vivo to ex vivo and hypothermic 8-12C to normothermic 35-37C The rationale behind perfusion is to restore the flow through the organs with a pump to provide oxygen and drugs
In normothermic regional perfusion NRP the physiological abdominal circulation is simulated with in vivo normothermic oxygenated perfusion during the first two hours after circulatory death NRP replaces SRR because this techniques allows a surgeon to retrieve the organs in a longer timeframe during this perfusion Also NRP can reverse early ischemia reduce ischemic type biliary lesions prevent surgical damage due to a more relax operation and the potential to test organs The possibility to test the organ during NRP enables a save environment to transplant livers from older DCD donors above 60 years old In many countries NRP is obligatory in DCD donation however this is not the current golden standard in the Netherlands Only in the Dutch Western region the livers of donors after circulatory death Maastricht type III and V above 50 years old will undergo NRP
Independently of age or region all DCD livers in the Netherlands will undergo dual hypothermic oxygenated perfusion DHOPE in the receiving hospital DHOPE is a dual through both portal vein and hepatic artery hypothermic ex vivo machine perfusion technique which depends on the presence of sufficient oxidative mitochondrial metabolism
subsequentially oxygenated mitochondria metabolize due to ischemia accumulated succinate and recharge adenosine tri-phosphate which leads to less reactive oxygen species less danger signaling and to reduced overall downstream inflammation during later normothermic reperfusion at implantation In comparison with SCS DHOPE has a significant reduction in postreperfusion syndrome early allograft dysfunction and non-anastomotic strictures after DCD For this reason this perfusion technique is incorporated in the Dutch national protocol for all DCD liver grafts and financed by personal health insurances High risk donor livers or livers from donors above sixty years old in the Northeastern region will additionally undergo controlled oxygenated rewarming normothermic machine perfusion COR-NMP after DHOPE Normothermic ex vivo machine perfusion has the opportunity to test ECD grafts before transplant The controlled oxygenated rewarming prevents sudden temperature shifts and subsequentially reduces ischemia reperfusion injury
The above mentioned techniques with either cold or warm perfusion serve two different goals cold perfusion DHOPE prevents cholangiopathy and warm perfusion NMPNRP can provide a testing area for the organ Considering two promising warm perfusion techniques in 2021 the new national protocol was written were NRP was performed in the west and NMP in the northeastern region To distinguish the differences between these techniques all the outcomes should be registered The question remains if NRP and COR-NMP are comparable to each other in patient outcome graft- and patient survival If these technique are equivalent in outcomes this techniques can be distinguished based on other characteristics such as utility cost effectiveness and influence on other organs The definition of utility is very broad but in this registration utilization is defined as the offer of a liver from a transplant coordinator to a successful transplant One other characteristic to distinguish between the different forms of perfusion is cost-effectiveness NRP may be more cost-effective than NMP since multiple organs are perfused in one procedure which could potentially also be beneficial for the other perfused organs As NRP also perfuses other organs the question remains how this organs respond on this perfusion technique For kidneys there is evidence that graft survival is similar after donation after brain death DBD NRP and SRR4 The pancreas will not be transplanted after NRP but in some cases the pancreas can be used for island isolation
In the context of a wide variety of different perfusion techniques in one small country the data of these different perfusion techniques are urgently needed to improve procurement graft outcome and preservation strategies
The persistent organ shortage has forced transplant programs to explore options to expand the organ supply Parallel to this interest in use of extended criteria donors ECD livers drove an evolution in current technique to retrieve preserve and improve livers before transplantation Before the era of perfusion the organs were retrieved by using standard rapid retrieval SRR and preserved by static cold storage SCS In 1930 researchers have explored machine perfusion as a technique to preserve organs but nowadays this technique has many more potentials including testing and improving Currently there is a wide diversity in different perfusion techniques varying from in vivo to ex vivo and hypothermic 8-12C to normothermic 35-37C The rationale behind perfusion is to restore the flow through the organs with a pump to provide oxygen and drugs
In normothermic regional perfusion NRP the physiological abdominal circulation is simulated with in vivo normothermic oxygenated perfusion during the first two hours after circulatory death NRP replaces SRR because this techniques allows a surgeon to retrieve the organs in a longer timeframe during this perfusion Also NRP can reverse early ischemia reduce ischemic type biliary lesions prevent surgical damage due to a more relax operation and the potential to test organs The possibility to test the organ during NRP enables a save environment to transplant livers from older DCD donors above 60 years old In many countries NRP is obligatory in DCD donation however this is not the current golden standard in the Netherlands Only in the Dutch Western region the livers of donors after circulatory death Maastricht type III and V above 50 years old will undergo NRP
Independently of age or region all DCD livers in the Netherlands will undergo dual hypothermic oxygenated perfusion DHOPE in the receiving hospital DHOPE is a dual through both portal vein and hepatic artery hypothermic ex vivo machine perfusion technique which depends on the presence of sufficient oxidative mitochondrial metabolism
subsequentially oxygenated mitochondria metabolize due to ischemia accumulated succinate and recharge adenosine tri-phosphate which leads to less reactive oxygen species less danger signaling and to reduced overall downstream inflammation during later normothermic reperfusion at implantation In comparison with SCS DHOPE has a significant reduction in postreperfusion syndrome early allograft dysfunction and non-anastomotic strictures after DCD For this reason this perfusion technique is incorporated in the Dutch national protocol for all DCD liver grafts and financed by personal health insurances High risk donor livers or livers from donors above sixty years old in the Northeastern region will additionally undergo controlled oxygenated rewarming normothermic machine perfusion COR-NMP after DHOPE Normothermic ex vivo machine perfusion has the opportunity to test ECD grafts before transplant The controlled oxygenated rewarming prevents sudden temperature shifts and subsequentially reduces ischemia reperfusion injury
The above mentioned techniques with either cold or warm perfusion serve two different goals cold perfusion DHOPE prevents cholangiopathy and warm perfusion NMPNRP can provide a testing area for the organ Considering two promising warm perfusion techniques in 2021 the new national protocol was written were NRP was performed in the west and NMP in the northeastern region To distinguish the differences between these techniques all the outcomes should be registered The question remains if NRP and COR-NMP are comparable to each other in patient outcome graft- and patient survival If these technique are equivalent in outcomes this techniques can be distinguished based on other characteristics such as utility cost effectiveness and influence on other organs The definition of utility is very broad but in this registration utilization is defined as the offer of a liver from a transplant coordinator to a successful transplant One other characteristic to distinguish between the different forms of perfusion is cost-effectiveness NRP may be more cost-effective than NMP since multiple organs are perfused in one procedure which could potentially also be beneficial for the other perfused organs As NRP also perfuses other organs the question remains how this organs respond on this perfusion technique For kidneys there is evidence that graft survival is similar after donation after brain death DBD NRP and SRR4 The pancreas will not be transplanted after NRP but in some cases the pancreas can be used for island isolation
In the context of a wide variety of different perfusion techniques in one small country the data of these different perfusion techniques are urgently needed to improve procurement graft outcome and preservation strategies
Study Oversight
Has Oversight DMC:
None
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?:
None