We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05520320
Recruitment Status : Recruiting
First Posted : August 29, 2022
Last Update Posted : September 1, 2022
Sponsor:
Collaborator:
University of Zurich
Information provided by (Responsible Party):
Vincent E. De Meijer, University Medical Center Groningen

Brief 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).

Condition or disease Intervention/treatment
Organ Preservation Liver Transplantation Hypothermic Machine Perfusion Device: Hypothermic oxygenated machine perfusion (any device)

Layout table for study information
Study Type : Observational
Estimated Enrollment : 800 participants
Observational Model: Cohort
Time Perspective: Retrospective
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)
Actual Study Start Date : August 24, 2022
Estimated Primary Completion Date : January 1, 2023
Estimated Study Completion Date : March 1, 2023

Resource links provided by the National Library of Medicine



Intervention Details:
  • 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.


Primary Outcome Measures :
  1. Death-censored graft survival, assessed by survival analysis methods [ Time Frame: Up to 5-years ]
    Defined as time from liver transplantation until re-transplantation or death due to graft dysfunction


Secondary Outcome Measures :
  1. Overall graft survival [ Time Frame: Up to 5-years ]
    Defined as time from liver transplantation until re-transplantation or all-cause death

  2. Overall patient survival [ Time Frame: Up to 5-years ]
    Defined as time from liver transplantation until all-cause death

  3. Arterial and biliary complication-free survival (ABCFS) [ Time Frame: Up to 5-years ]
    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)

  4. Incidence of biliary complications [ Time Frame: Up to 5-years ]

    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

  5. Incidence of vascular complications [ Time Frame: Up to 5-years ]

    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

  6. Incidence of acute cellular rejection [ Time Frame: Up to 5-years ]
    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)

  7. Incidence of chronic rejection [ Time Frame: Up to 5-years ]
    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)

  8. Incidence of re-transplantation [ Time Frame: Up to 5-years ]
    Defined as proportion of patients who underwent liver re-transplantation for any cause

  9. Incidence of recurrence of primary disease (including recurrence of malignancies) [ Time Frame: Up to 5-years ]
    Defined as histological or radiologically confirmed recurrence

  10. Incidence of new-onset chronic kidney disease [ Time Frame: Up to 5-years ]
    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)

  11. Incidence of new-onset diabetes after transplantation [ Time Frame: Up to 5-years ]
    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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.
Criteria

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 01.01.2015 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05520320


Contacts
Layout table for location contacts
Contact: Isabel MA Brüggenwirth, MD, PhD +31652671523 i.m.a.bruggenwirth@umcg.nl
Contact: Janina Eden, MD janina.eden@usz.ch

Locations
Layout table for location information
Netherlands
University Medical Center Groningen Recruiting
Groningen, Netherlands
Contact: Isabel MA Brüggenwirth, MD, PhD    +31652671523    i.m.a.bruggenwirth@umcg.nl   
Principal Investigator: Vincent E de Meijer, MD, PhD         
Switzerland
University Hospital Zürich Recruiting
Zürich, Switzerland
Contact: Janina Eden, MD       janina.eden@usz.ch   
Principal Investigator: Philipp Dutkowski, MD, PhD         
Sponsors and Collaborators
University Medical Center Groningen
University of Zurich
Investigators
Layout table for investigator information
Principal Investigator: Vincent E de Meijer, MD, PhD University Medical Center Groningen
Layout table for additonal information
Responsible Party: Vincent E. De Meijer, Principal Investigator, University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT05520320    
First Posted: August 29, 2022    Key Record Dates
Last Update Posted: September 1, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Hypothermia
Body Temperature Changes