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

Liver Transplantation Clinical Trial

— HOPE-REAL  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05520320
• Other study ID #: HOPE-REAL study
• Status: Completed
• Start date: August 24, 2022
• Est. completion date: August 1, 2023

Study information

• Verified date: April 2024
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1202
• Est. completion date: August 1, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hypothermia
• Liver Transplantation
• Organ Preservation

Intervention

Device:
• Hypothermic oxygenated machine perfusion (any device)
After static cold storage, all grafts included in this study are subjected to >1 hour of hypothermic oxygenated machine perfusion at 4-12°C with an acellular perfusion solution.

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen
Switzerland	University Hospital Zürich	Zürich

Sponsors (2)

Lead Sponsor	Collaborator
University Medical Center Groningen	University of Zurich

Countries where clinical trial is conducted

Netherlands,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall graft survival	Defined as time from liver transplantation until re-transplantation or all-cause death	Up to 5-years
Secondary	Overall patient survival	Defined as time from liver transplantation until all-cause death	Up to 5-years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Incidence of re-transplantation	Defined as proportion of patients who underwent liver re-transplantation for any cause	Up to 5-years
Secondary	Incidence of recurrence of primary disease (including recurrence of malignancies)	Defined as histological or radiologically confirmed recurrence	Up to 5-years
Secondary	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
Secondary	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