Ignite Creation Date:
2024-05-06 @ 3:44 PM
Last Modification Date:
2024-10-26 @ 1:56 PM
Study NCT ID:
NCT04744389
Status:
UNKNOWN
Last Update Posted:
2022-07-26
First Post:
2021-01-18
Brief Title:
Comparison of Hypothermic Versus Normothermic Ex-vivo Preservation
Sponsor:
Azienda Ospedaliero Universitaria Pisana
Organization:
Azienda Ospedaliero Universitaria Pisana
Study Overview
Official Title:
Optimization of an Evidence-based Organizational Model of Liver and Pancreas Transplant Using Cardiac Death Donors a Pilot Prospective Randomized Multicenter Study for the Comparison of Hypothermic Versus Normothermic Ex-vivo Preservation
Status:
UNKNOWN
Status Verified Date:
2022-07
Last Known Status:
RECRUITING
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:
DCDNet
Brief Summary:
Study groups
The study is a multicenter Pisa and Milan prospective randomized study comparing D-HOPE HMP vs NMP in DCD and ECD-DBD extended criteria brain-dead donors Once a DCD or a DBD with extended criteria ECD-DBD meets the inclusion criteria they are randomized as follow
1 20 liver grafts from DCD after normothermic regional perfusion NRP matching the inclusion criteria are randomized 11 to hypothermic machine perfusion HMP vs normothermic machine perfusion NMP and then transplanted
2 40 liver grafts from ECD-DBD matching the inclusion criteria are randomized 11 to hypothermic machine perfusion HMP vs normothermic machine perfusion NMP and then transplanted
The study is a multicenter Pisa and Milan prospective randomized study comparing D-HOPE HMP vs NMP in DCD and ECD-DBD extended criteria brain-dead donors Once a DCD or a DBD with extended criteria ECD-DBD meets the inclusion criteria they are randomized as follow
1 20 liver grafts from DCD after normothermic regional perfusion NRP matching the inclusion criteria are randomized 11 to hypothermic machine perfusion HMP vs normothermic machine perfusion NMP and then transplanted
2 40 liver grafts from ECD-DBD matching the inclusion criteria are randomized 11 to hypothermic machine perfusion HMP vs normothermic machine perfusion NMP and then transplanted
Detailed Description:
The persistent mismatch between patients waiting for a liver transplant LT and grafts availability promoted the use of donation after circulatory death DCD Italian law requires 20 minutes of continous flatline electrocardiogram to declared individuals circulatory death and such a long period of warm ischemia time forced the development of protocols using abdominal normothermic regional perfusion NRP followed by ex-vivo graft reperfusion by means of machine perfusion technology MP for its potential to minimize ischemiareperfusion damage and promote organ repair and reconditioning prior to transplantation An extensive evaluation of all DCD donors might increase donation rate by 30 but while kidney transplant from DCD donors is well implemented no definitive data exist on the optimal use of NRP and MP in liver and pancreas transplantation and an organizational model is far to be implemented Moreover a randomized trial comparing hypothermic vs normothermic ex-vivo perfusion has never been performed The proposed project will perform a pilot open randomized prospective trials to evaluate the sequential use of NRP followed by ex-vivo MP hypothermic HMP vs normothermic NMP by measuring several indicators of organ damage and recovery with the target to set up the optimal organizational model for DCD donation
1 Twenty LT from DCD donors after NRP considered transplantable for the acceptance criteria in use will be randomized 11 to ex-vivo HMP or NMP multicenter study together with the center in Milan
2 40 liver grafts from ECD-DBD matching the inclusion criteria are randomized 11 to hypothermic machine perfusion HMP vs normothermic machine perfusion NMP and then transplanted To assess organ damage and repair capacity the following investigations will be performed -biomarkers of apoptosis necrosis innate-mediated inflammation and its resolution angiogenesis and thrombosis during NRP -circulating biomarkers indicating damage proliferation angiogenetic and tissue remodelling factors a targeted-metabolomic and lipidomic profiling during ex-vivo HMP or NMP in the perfusate and on blood samples in the peri and post-operative period bile composition on graft subjected to NMP Evaluation of necrosis apoptosis and proliferation immunohistochemical analysis a targeted-metabolomic and lipidomic profiling ATP measurement and electronic microscopy investigations will be performed on liver tissue and bile duct biopsies after NRP before and after ex-vivo reperfusion and immediately after reperfusion in the recipient only for transplantable grafts Based on the collected data a new algorithm of organ evaluation procurement preservation and reconditioning will be formulated and disseminated
1 Twenty LT from DCD donors after NRP considered transplantable for the acceptance criteria in use will be randomized 11 to ex-vivo HMP or NMP multicenter study together with the center in Milan
2 40 liver grafts from ECD-DBD matching the inclusion criteria are randomized 11 to hypothermic machine perfusion HMP vs normothermic machine perfusion NMP and then transplanted To assess organ damage and repair capacity the following investigations will be performed -biomarkers of apoptosis necrosis innate-mediated inflammation and its resolution angiogenesis and thrombosis during NRP -circulating biomarkers indicating damage proliferation angiogenetic and tissue remodelling factors a targeted-metabolomic and lipidomic profiling during ex-vivo HMP or NMP in the perfusate and on blood samples in the peri and post-operative period bile composition on graft subjected to NMP Evaluation of necrosis apoptosis and proliferation immunohistochemical analysis a targeted-metabolomic and lipidomic profiling ATP measurement and electronic microscopy investigations will be performed on liver tissue and bile duct biopsies after NRP before and after ex-vivo reperfusion and immediately after reperfusion in the recipient only for transplantable grafts Based on the collected data a new algorithm of organ evaluation procurement preservation and reconditioning will be formulated and disseminated
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