Long-term Outcomes After Hypothermic Oxygenated Machine Perfusion of Donor Livers Using Real-world Data (HOPE-REAL)

Assessment of Long-term Outcomes After Transplantation of Donor Livers Preserved by Hypothermic Oxygenated Machine Perfusion (HOPE): a Retrospective Cohort Analysis of Real-world Data (IDEAL-D Stage 4)

End-ischemic hypothermic oxygenated machine perfusion (HOPE) of human donor livers mitigates ischemia-reperfusion injury, resulting in a reduction of post-reperfusion syndrome, early allograft dysfunction and biliary complications, when compared with static cold storage. According to IDEAL-D (Idea, Development, Exploration, Assessment, Long term study-Framework for Devices), with several published randomized controlled trials on short-to-medium term outcomes, scientific evidence for HOPE has currently reached stage 3. Assessment of long-term outcomes after HOPE preservation based on real-world data (i.e., IDEAL-D stage 4) is currently still lacking. Therefore, we aim to conduct an international, multi-center, retrospective, observational cohort study to assess long-term outcomes after transplantation of donor livers preserved by hypothermic oxygenated machine perfusion (HOPE).

Study Overview

• Status: Completed
• Conditions: Liver Transplantation; Organ Preservation; Hypothermic Machine Perfusion
• Intervention / Treatment: Device: Hypothermic oxygenated machine perfusion (any device)

• Study Type: Observational
• Enrollment (Actual): 1202

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands
    • University Medical Center Groningen
• Switzerland
  • Zürich, Switzerland
    • University Hospital Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adult patients (>18 years) undergoing liver transplantation of donor livers preserved with end-ischemic HOPE.

Description

Inclusion Criteria:

• Adult patients (>18 years) who underwent liver transplantation of donor livers preserved with end-ischemic HOPE (including donation after normothermic regional perfusion) between 01.01.2012 and 31.12.2021.

Exclusion Criteria:

• Simultaneous multiorgan transplantations, sequential normothermic machine perfusion (e.g., DHOPE-COR-NMP, but not NRP), living partial liver donation.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death-censored graft survival, assessed by survival analysis methods	Defined as time from liver transplantation until re-transplantation or death due to graft dysfunction	Up to 5-years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall graft survival	Defined as time from liver transplantation until re-transplantation or all-cause death	Up to 5-years
Overall patient survival	Defined as time from liver transplantation until all-cause death	Up to 5-years
Arterial and biliary complication-free survival (ABCFS)	Defined as time from liver transplantation until occurrence of an arterial or biliary complication of Dindo-Clavien grade ≥3, dated at the time of interventional, endoscopic, or surgical treatment required to correct it (Savier E, De Rycke Y, Lim C, et al. Novel Composite Endpoint for Assessing Outcomes in Liver Transplantation: Arterial and Biliary Complication-Free Survival. Liver Transpl. 2022;28(1):75-87. doi:10.1002/lt.26269)	Up to 5-years
Incidence of biliary complications	Defined as a composite of: Non-anastomotic biliary strictures: any irregularity or narrowing of the lumen of the intrahepatic or extrahepatic donor bile ducts, excluding the biliary anastomosis, diagnosed with the use of cholangiography in combination with clinical symptoms (e.g., jaundice or cholangitis) or an elevation of cholestatic laboratory variables, in the presence of a patent hepatic artery; Anastomotic biliary strictures: strictures occurring at the anastomosis of donor choledochal duct and recipient choledochal duct or jejunal Roux-limb; Biliary leakage: fluid with an elevated (>3x serum) bilirubin level in the abdominal drain or intra-abdominal fluid on or after post-operative day 3 or the need for radiological intervention (i.e. interventional drainage) owing to biliary collections or re-laparotomy due to biliary peritonitis	Up to 5-years
Incidence of vascular complications	Defined as a composite of: Hepatic arterial thrombosis: radiologically or surgically proven thrombosis of the hepatic artery; Portal vein thrombosis: radiologically or surgically proven thrombosis of the portal vein; Venous outflow tract obstruction: radiologically or surgically proven thrombosis of the main hepatic veins or the inferior vena cava	Up to 5-years
Incidence of acute cellular rejection	Defined as biopsy proven Banff grade 2 or 3 rejection (Demetris AJ, Bellamy C, Hübscher SG, et al. 2016 Comprehensive Update of the Banff Working Group on Liver Allograft Pathology: Introduction of Antibody-Mediated Rejection. Am J Transplant. 2016;16(10):2816-2835. doi:10.1111/ajt.13909)	Up to 5-years
Incidence of chronic rejection	Defined as histopathological evidence of immunologic injury with irreversible damage to the bile ducts, arteries, and veins (Demetris A, Adams D, Bellamy C, et al. Update of the International Banff Schema for Liver Allograft Rejection: working recommendations for the histopathologic staging and reporting of chronic rejection. An International Panel. Hepatology. 2000;31(3):792-799. doi:10.1002/hep.510310337)	Up to 5-years
Incidence of re-transplantation	Defined as proportion of patients who underwent liver re-transplantation for any cause	Up to 5-years
Incidence of recurrence of primary disease (including recurrence of malignancies)	Defined as histological or radiologically confirmed recurrence	Up to 5-years
Incidence of new-onset chronic kidney disease	Defined as renal impairment (kidney morphology, pathology, imaging, blood or urine composition abnormalities) persisting for >3 months with or without eGFR decrease, and/or eGFR <60 for >3 months with or without renal impairment (Levey AS, Eckardt K-U, Tsukamoto Y, et al. Definition and Classification of Chronic Kidney Disease: A Position Statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2005 Jun;67(6):2089-100. doi: 10.1111/j.1523-1755.2005.00365.x)	Up to 5-years
Incidence of new-onset diabetes after transplantation	Defined as symptoms of diabetes plus casual plasma glucose levels ≥200 mg/dL (11.1 mmol/L) or fasting plasma glucose ≥126 mg/dL (7.0 mmol/L) or 2 hours plasma glucose ≥200 mg/dL (11.1 mmol/L during an oral glucose tolerance testing (Davidson J, Wilkinson A, Dantal J, et al. New-onset diabetes after transplantation: 2003 International consensus guidelines. Proceedings of an international expert panel meeting. Barcelona, Spain, 19 February 2003. Transplantation. 2003;75(10 Suppl):SS3-24. doi:10.1097/01.TP.0000069952.49242.3E)	Up to 5-years

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Collaborators: University of Zurich
• Investigators: Principal Investigator: Vincent E de Meijer, MD, PhD, University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2022
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): August 1, 2023

Study Registration Dates

• First Submitted: August 25, 2022
• First Submitted That Met QC Criteria: August 25, 2022
• First Posted (Actual): August 29, 2022

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Body Temperature Changes; Hypothermia
• Other Study ID Numbers: HOPE-REAL study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No