- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05327478
NRP vs DHOPE vs COR-NMP in ECD-DCD Donation
Direct Comparison of NRP With DHOPE and COR-NMP to Maximize the Use of ECD After DCD Donation in the Netherlands
Study Overview
Status
Intervention / Treatment
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 (8-12°C) to normothermic (35-37°C). 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 (NMP/NRP) 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 SRR.4 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 Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Jeroen de Jonge, Dr.
- Phone Number: +31643904182
- Email: j.dejonge.1@erasmusmc.nl
Study Contact Backup
- Name: Fenna J van der Heijden, Drs.
- Phone Number: +31638406398
- Email: f.vanderheijden@erasmusmc.nl
Study Locations
-
-
Zuid-Holland
-
Rotterdam, Zuid-Holland, Netherlands
- Recruiting
- Erasmus MC
-
Contact:
- Jeroen de Jonge, Dr.
- Phone Number: +31643904182
- Email: j.dejonge.1@erasmusmc.nl
-
Contact:
- Fenna J van der Heijden, Drs.
- Phone Number: +31638406398
- Email: f.vanderheijden@erasmusmc.nl
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion criteria:
- DCD donor (Maastricht type III and V)
- Age above 50 years old and below 75 years old
Exclusion criteria:
- Malignancy (except for primary non-metastatic central nervous system tumors, non-melanoma skin tumors or cured malignancies)
- Active infection (sepsis, meningitis, human immune deficiency virus, rubella, rabies, herpes zoster, tuberculosis)
- Intravenous drug abuse
- Unknown cause of death
- In the case of a NRP procedure: donors with a BMI above 35 and transaminases above 1000 U/I and not decreasing prior to donation are excluded
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Non ECD
50-60 years old AND non ECD
|
Normothermic Regional Perfusion
Dual Hypothermic Oxygenated Perfusion
|
ECD
>60 years old or ECD
|
Normothermic Regional Perfusion
Dual Hypothermic Oxygenated Perfusion
Controlled Oxygenated Rewarming Normothermic Machine Perfusion
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Organ utilization rate in percentage
Time Frame: 01-01-2022 to 01-05-2023
|
Number of transplanted organs divided by number offered organs
|
01-01-2022 to 01-05-2023
|
Survival in days
Time Frame: 1 year post transplantation
|
Patient and graft survival
|
1 year post transplantation
|
Cost effectiveness in difference between treatments in euro's
Time Frame: One year post transplantation
|
All medical costs resulting from treatment
|
One year post transplantation
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cumulative complications summarized by the comprehensive complication index (CCI)
Time Frame: One year post transplantation
|
Complications will be ranked by the CCI
|
One year post transplantation
|
Number of patients with Ischemic cholangiopathy (IC) and anastomotic strictures (AS)
Time Frame: One year post transplantation
|
IC is also referred to as non-anastomotic strictures (NAS) or ischemic type biliary lesions (ITBL).
IC is defined as a symptomatic patient (e.g., jaundice or cholangitis) with radiological proven irregularity or lumen narrowing in the intra- or extrahepatic donor bile duct in absence of hepatic artery thrombosis.
Isolated strictures at the anastomosis are anastomotic strictures.
|
One year post transplantation
|
Length of stay
Time Frame: During peritransplant admission, up to discharge.
|
Length of stay in the hospital during the peritransplant admission, measured in days after the transplantation excluding readmission.
Also, length of stay on the intensive care unit during the peritransplant admission, including readmission.
|
During peritransplant admission, up to discharge.
|
Number of patients with Early allograft dysfunction (EAD)
Time Frame: Post operative day 90
|
EAD is defined as patient or graft death before the post-operative day (POD) 90
|
Post operative day 90
|
Waiting list time in days
Time Frame: 01-01-2022 to 01-05-2023
|
Per center
|
01-01-2022 to 01-05-2023
|
Waitlist mortality in percentage
Time Frame: 01-01-2022 to 01-05-2023
|
Per center
|
01-01-2022 to 01-05-2023
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Jeroen de Jonge, Dr., Erasmus Medical Center
Publications and helpful links
General Publications
- de Vries Y, Matton APM, Nijsten MWN, Werner MJM, van den Berg AP, de Boer MT, Buis CI, Fujiyoshi M, de Kleine RHJ, van Leeuwen OB, Meyer P, van den Heuvel MC, de Meijer VE, Porte RJ. Pretransplant sequential hypo- and normothermic machine perfusion of suboptimal livers donated after circulatory death using a hemoglobin-based oxygen carrier perfusion solution. Am J Transplant. 2019 Apr;19(4):1202-1211. doi: 10.1111/ajt.15228. Epub 2019 Jan 23.
- van Rijn R, Schurink IJ, de Vries Y, van den Berg AP, Cortes Cerisuelo M, Darwish Murad S, Erdmann JI, Gilbo N, de Haas RJ, Heaton N, van Hoek B, Huurman VAL, Jochmans I, van Leeuwen OB, de Meijer VE, Monbaliu D, Polak WG, Slangen JJG, Troisi RI, Vanlander A, de Jonge J, Porte RJ; DHOPE-DCD Trial Investigators. Hypothermic Machine Perfusion in Liver Transplantation - A Randomized Trial. N Engl J Med. 2021 Apr 15;384(15):1391-1401. doi: 10.1056/NEJMoa2031532. Epub 2021 Feb 24.
- van de Leemkolk FEM, Schurink IJ, Dekkers OM, Oniscu GC, Alwayn IPJ, Ploeg RJ, de Jonge J, Huurman VAL. Abdominal Normothermic Regional Perfusion in Donation After Circulatory Death: A Systematic Review and Critical Appraisal. Transplantation. 2020 Sep;104(9):1776-1791. doi: 10.1097/TP.0000000000003345.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- EMC-NRP2-2022
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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