No registrations found.
Source
Brief title
Health condition
End-stage liver disease needing liver transplantation
Sponsors and support
Intervention
Outcome measures
Primary outcome
To study the feasibility and safety of end-ischemic DHOPE-PRO (≥4 hours) of donor livers, by assessing the occurrence of preservation-related SAEs and SADEs during machine perfusion (including graft discard during perfusion), and within 30 days after transplantation.
Secondary outcome
• Biliary complications (including anastomotic and non-anastomotic biliary strictures) leading to a surgical or endoscopic intervention within 12 months after liver transplantation.
• Actuarial graft and patient survival at 12 months after liver transplantation.
• Incidence of acute kidney injury according to the KDIGO criteria27.
• Biochemical analysis of graft function and ischemia-reperfusion injury at postoperative day 0-10, and at 1, 3, 6, and 12 months after transplantation, including serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, total bilirubin, and international normalized ratio, and with the calculation of graft function assessment scores, including Model for Early Allograft Function (MEAF)28 and Liver Graft Assessment Following Transplantation (L-GrAFT).29
• Length of stay at the intensive-care-unit and total hospital length of stay
• Perfusion characteristics during DHOPE, including vascular flow, pressure, resistance, and oxygenation and temperature of the perfusate at every 30 minutes
• Postoperative complications according to the Clavien-Dindo classification as well as the comprehensive complications index30 within 30 days after liver transplantation.
Background summary
Introduction: End-ischemic preservation of a donor liver by dual hypothermic oxygenated machine perfusion (DHOPE) for 2 hours prior to transplantation is sufficient to mitigate ischemia-reperfusion damage and fully restore cellular energy levels. Clinical studies have shown beneficial outcomes after transplantation of liver grafts preserved by DHOPE compared to static cold storage. In addition to graft reconditioning, DHOPE may also be used to prolong preservation time, which could facilitate logistics for allocation and transplantation globally.
Methods and analysis: This is a prospective, pseudo-randomised, dual-arm, IDEAL-D Stage 2 clinical device trial designed to determine safety and feasibility of prolonged DHOPE (DHOPE-PRO). The end-time of the donor hepatectomy will determine whether the graft will be assigned to the intervention (4:00 p.m.-3:59 a.m.) or to the control arm (4:00 a.m.-3:59 p.m.). In total, 36 livers will be included in the study. Livers in the intervention group (n=18) will undergo DHOPE-PRO (≥4 hours) until implantation the following morning, whereas livers in the control group (n=18) will undergo regular DHOPE (2 hours) prior to implantation. The primary endpoint of this study is a composite of the occurrence of all (serious) adverse events during DHOPE and up to 30 days after liver transplantation.
Ethics and dissemination: The protocol was approved by the Medical Ethical Committee of Groningen, METc2020.126 in June 2020, and the study was registered in the Netherlands National Trial Registry prior to initiation
Study objective
During off-hours, DHOPE preservation of human donor livers can be safely prolonged (≥4 hours) until the next morning to enable transplantation at day time.
Study design
During machine perfusion, postoperative days 0-7 and 3,6,9,12 months after liver transplantation
Intervention
Prolonged end-ischemic DHOPE (8-12ºC) using a Liver Assist device until implantation the following morning (≥4 hours).
Inclusion criteria
Given informed consent
Adult patients (≥18 years old)
Donors with a body weight ≥40 kg
DCD (n=6 per arm) or DBD (n=12 per arm) grafts
Exclusion criteria
Simultaneous participation in another trial potentially influencing this trial
Simultaneous combined organ transplantation
Mental conditions rendering the subject incapable to understand the nature, scope, and consequences of the trial
HU status
Laboratory MELD score >30
Recipient tested positive for HIV
DCD Maastricht category V
DCD donors >60 years old
Donor with untreated HIV/HBV/HCV
Estimated graft steatosis >30%
Split or partial liver grafts
Domino donor livers
Living donor liver grafts
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
NTR-new | NL8740 |
Other | METC UMCG : 2020/126 |