Ignite Creation Date:
2024-05-06 @ 9:58 AM
Last Modification Date:
2024-10-26 @ 12:22 PM
Study NCT ID:
NCT03124641
Status:
COMPLETED
Last Update Posted:
2021-01-28
First Post:
2017-03-20
Brief Title:
HOPE for Human Extended Criteria and Donation After Brain Death Donor ECD-DBD Liver Allografts
Sponsor:
University Hospital Aachen
Organization:
University Hospital Aachen
Study Overview
Official Title:
Hypothermic Oxygenated Machine Perfusion HOPE for Liver Transplantation of Human Liver Allografts From Extended Criteria Donors ECD in Donation After Brain Death DBD a Multicenter Randomized Controlled Trial HOPE ECD-DBD
Status:
COMPLETED
Status Verified Date:
2021-01
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:
HOPE-ECD-DBD
Brief Summary:
The purpose of this study is to test the effects of hypothermic oxygenated machine perfusion HOPE in a phase-II prospective multicenter randomized clinical trial RCT on extended criteria donor allografts ECD in donation after brain death DBD orthotropic liver-transplantation OLT HOPE-ECD-DBD Human whole organ liver grafts will be submitted to 1-2 hours of HOPE via the portal vein directly before implantation and going to be compared to a control-group of patients transplanted after conventional cold storage CCS Primary early graft injury and secondary eg postoperative complications hospital stay survival objectives are going to be analysed in a 12 month follow up Ischemia-reperfusion IR injury and inflammation will be assessed using liver tissue serum and bile samples as well as machine perfusion perfusate
To improve the availability of donor allografts and reduce waiting list mortality graft acceptance criteria were extended increasingly over the decades The use of extended criteria donor ECD allografts is associated with higher incidences of primary graft non-function PNF andor delayed graft function DGF As such several strategies have been developed aiming at reconditioning poor quality ECD grafts HOPE has been tested intensively in pre-clinical animal experiments Although its known that HOPE can exert its reconditioning effect via cellular and mitochondrial pathways in the endothelial and parenchymal cells there is still scarce evidence available on the exact subcellular mechanism of HOPE induced organ protection in the clinical scenario of liver transplantation In donation after cardiac death DCD OLT the positive effects of HOPE have been shown to reduce the incidence of biliary complications mitochondrial damage and improve the overall cellular energy-status
In the HOPE setting organ perfusion is performed in the transplant center shortly before the actual implantation with oxygenated perfusate using an extra corporal organ perfusion system The first clinical study with this promising technique was recently reported in a Swiss cohort of patients who received DCD allografts In organ donation after brain death DBD the only legally accepted approach for organ donation in most countries HOPE and its effect on early graft injury and postoperative complications remains to be elucidated
To improve the availability of donor allografts and reduce waiting list mortality graft acceptance criteria were extended increasingly over the decades The use of extended criteria donor ECD allografts is associated with higher incidences of primary graft non-function PNF andor delayed graft function DGF As such several strategies have been developed aiming at reconditioning poor quality ECD grafts HOPE has been tested intensively in pre-clinical animal experiments Although its known that HOPE can exert its reconditioning effect via cellular and mitochondrial pathways in the endothelial and parenchymal cells there is still scarce evidence available on the exact subcellular mechanism of HOPE induced organ protection in the clinical scenario of liver transplantation In donation after cardiac death DCD OLT the positive effects of HOPE have been shown to reduce the incidence of biliary complications mitochondrial damage and improve the overall cellular energy-status
In the HOPE setting organ perfusion is performed in the transplant center shortly before the actual implantation with oxygenated perfusate using an extra corporal organ perfusion system The first clinical study with this promising technique was recently reported in a Swiss cohort of patients who received DCD allografts In organ donation after brain death DBD the only legally accepted approach for organ donation in most countries HOPE and its effect on early graft injury and postoperative complications remains to be elucidated
Detailed Description:
The present RCT comprises two groups a perfusion group 1 HOPE and a control conventional cold storage group 2 CCS group Patients with proven written informed consent on waiting list for orthotopic liver transplantation will be recruited Randomization is performed with an online randomizing tool for clinical trials wwwrandomizerat at the time of allograft arrival at the transplant center and acceptance of the organ for transplantation Stratified randomization model will be used to ensure balance of prognostic variables between the treatment groups
In case of randomisation to group 1 HOPE will be applied to the allograft in the operation room directly after the back table preparation The application of HOPE to the liver allograft will not delay the implantation due to the fact that it is performed parallel to the recipient hepatectomy
Commercially available and machine-perfusion approved Belzer MPS UW solution Belzer Organ Preservation Solutions Bridge for Life will be used as perfusate for machine perfusion
Patients will be followed for one year after OLT
Interim analysis After n12 per randomized group is reached data will be analyzed by an independent Data Monitoring Committee The RCT will be stopped if one of the following criteria is reached
Significantly higher serum ALT levels p0001 using Students t-test in the HOPE group compared to the CCS group Efficacy
The proportion of Grade III complications is significantly higher p005 Fischers exact test in the HOPE group when compared to the CCS group Safety
In case of randomisation to group 1 HOPE will be applied to the allograft in the operation room directly after the back table preparation The application of HOPE to the liver allograft will not delay the implantation due to the fact that it is performed parallel to the recipient hepatectomy
Commercially available and machine-perfusion approved Belzer MPS UW solution Belzer Organ Preservation Solutions Bridge for Life will be used as perfusate for machine perfusion
Patients will be followed for one year after OLT
Interim analysis After n12 per randomized group is reached data will be analyzed by an independent Data Monitoring Committee The RCT will be stopped if one of the following criteria is reached
Significantly higher serum ALT levels p0001 using Students t-test in the HOPE group compared to the CCS group Efficacy
The proportion of Grade III complications is significantly higher p005 Fischers exact test in the HOPE group when compared to the CCS group Safety
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