Bridge to HOPE: Hypothermic Oxygenated Perfusion Versus Cold Storage Prior to Liver Transplantation

A Multicenter, Prospective, Open-label, Randomized Controlled Clinical Trial to Compare the Safety and Effectiveness of the VitaSmart Liver Machine Perfusion System With Static Cold Storage for Organ Preservation Prior to Liver Transplantation

This is a prospective, multi-center, controlled, randomized, pivotal study to evaluate the safety and effectiveness of the VitaSmart Liver Machine Perfusion System by comparing clinical outcomes in patients undergoing liver transplantation with ex-vivo liver preservation using static cold storage (SCS) followed by hypothermic oxygenated machine perfusion (HOPE) versus SCS only.

Study Overview

• Status: Active, not recruiting
• Conditions: Liver Failure; End Stage Liver DIsease
• Intervention / Treatment: Device: VitaSmart Liver Machine Perfusion System; Other: Static cold storage

Detailed Description

Patients on the UNOS waiting list for liver transplantation who have been consented, meet study eligibility criteria and are matched to a liver allograft from donation after brain death (DBD) or donation after circulatory death (DCD) that meet the extended risk eligibility criteria will be randomized 1:1 to SCS followed by HOPE (HOPE arm) or to SCS only (SCS arm). The objective of the study is to demonstrate the safety and effectiveness of the VitaSmart Liver Machine by comparing endpoints between the HOPE and SCS arms.

Following transplantation, patients will be monitored daily (labs, adverse events, medications/procedures) while inpatient, and then additionally on Days 14 and 30 and Months 3, 6 and 12. The primary efficacy endpoint of early allograft dysfunction (EAD) rate will be assessed between HOPE and control using a non-inferiority design. An interim analysis is planned after approximately 70% of patients have been completed primary endpoint data collection to assess for early study completion based on non-inferiority or superiority.

• Study Type: Interventional
• Enrollment (Anticipated): 244
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chriss Stanford, MA; Phone Number: 720-201-1640; Email: c.stanford@b2ll.com
• Study Contact Backup: Name: Donna Corum; Phone Number: 847-963-3070; Email: d.corum@b2ll.com

Study Locations

• United States
  • California
    • San Bernardino, California, United States, 92408
      • Loma Linda University Medical Center
    • San Francisco, California, United States, 94143
      • University of California San Francisco
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
    • Weston, Florida, United States, 33331
      • Cleveland Clinic
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Massachusetts
    • Burlington, Massachusetts, United States, 01895
      • Lahey Hospital and Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University St. Louis
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Nebraska Medical Center
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Donation after Brain Death (DBD) Liver Inclusion Criteria (one or more):

• Donor age 50-85 years
• Anticipated cold ischemia time 10-15 hours (excluding HOPE duration)
• Macrosteatosis 10-40%
• Terminal ALT 250-1500 IU/ml
• Peak ALT within 3 days 1000-3000 IU/ml
• Terminal total bilirubin 2-4 mg/dl

Donation after Brain Death (DBD) Liver Exclusion Criteria (one or more):

• Donor age <18 or >85 years
• Anticipated cold ischemia >15 hours
• Macrosteatosis >40%
• Terminal ALT >1500 IU/ml
• Peak ALT within 3 days >3000 IU/ml
• Terminal total bilirubin >4 mg/dl
• Presence of hemodynamic and/or anatomical donor abnormalities that, in the opinion of the Investigator, make the liver allograft unsuitable for transplant into the recipient subject
• Liver intended for split transplant
• Liver from living donor
• Donor terminal serum Na >160 mmol/L

Donation after Cardio-circulatory Death (DCD) Liver Inclusion Criteria (all):

• Donor age 18-60 years
• Anticipated cold ischemia time <12 hours (excluding HOPE duration)
• Functional warm ischemia time ≤35 minutes, defined as interval from the time of onset of donor hypotension (MAP <50mmHg) until the time of donor cross clamp
• Macrosteatosis ≤20%
• Terminal ALT ≤500 IU/ml
• Peak ALT within 3 days ≤2000 IU/ml
• Terminal total bilirubin ≤3 mg/dl

Donation after Cardio-circulatory Death (DCD) Liver Exclusion Criteria (one or more):

• Presence of hemodynamic and/or anatomical donor abnormalities that, in the opinion of the Investigator, make the liver allograft unsuitable for transplant into the recipient subject
• Liver intended for split transplant
• Liver from living donor
• Donor terminal serum Na >160 mmol/L

Recipient Inclusion Criteria (one or more):

• Subject (or legally authorized representative) is able to provide informed consent and HIPAA authorization
• Subject is male or female and at least 18 years of age
• Subject is registered as an active liver recipient on the UNOS waiting list for liver transplantation
• Subject will undergo primary liver transplantation
• Subject is willing to comply with the study requirements and procedures
• Subject with hepatocellular carcinoma as indication for Orthotopic Liver Transplantation; the tumor must be within Milan Criteria or down-staged to Milan Criteria

Recipient Exclusion Criteria (one or more):

• Subject will undergo multiple organ transplantations (liver-kidney, liver-lung, etc.)
• Subject is listed for liver transplantation due to fulminant liver failure (UNOS status 1A)
• Subject is pregnant
• Subject is on respiratory (ventilator dependent) and/or cardiocirculatory support (requires at least one intravenous inotrope to maintain hemodynamics)
• Subject is enrolled in an interventional clinical trial with an investigational drug or device

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hypothermic oxygenated perfusion (HOPE); Ex-vivo donor liver preservation using static cold storage followed by HOPE using the VitaSmart Liver Machine	Device: VitaSmart Liver Machine Perfusion System; Following donor liver retrieval, preservation using static cold storage, and back table preparation in the transplant center operating room, the organ will be flushed with Belzer UW Machine Perfusion Solution (MPS) and perfused through the cannulated portal vein using cold, actively oxygenated MPS that is circulated at low pressure for 90 minutes to 5 hours. After disconnection from the device, donor liver implantation and reperfusion will proceed in accordance with institutional care standards.; Other Names: VitaSmart Liver Machine; Hypothermic oxygenated perfusion; Other: Static cold storage; Donor liver retrieval and preservation using standard of care cold storage methods
Other: Static cold storage; Ex-vivo donor liver preservation using static cold storage only	Other: Static cold storage; Donor liver retrieval and preservation using standard of care cold storage methods

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with early allograft dysfunction (EAD)	At Day 7 post-transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Model for early allograft function (MEAF) score	Based on definition by Olthoff et al, 2010 (doi: 10.1002/lt.22091)	Within 3 days post-transplant
Proportion of patients with primary non-function (PNF)	Based on definition by Pareja et al, 2015 (doi: 10.1002/lt.23990)	Within 7 days post-transplant
Length of hospital stay	Duration from initial ICU admission to hospital discharge order (measured in days)	Up to study participation ends at 1-year follow-up
Length of intensive care unit stay	Duration from initial ICU admission to ICU discharge order (measured in days)	Up to study participation ends at 1-year follow-up
Duration on dialysis	Duration from establishment of graft reperfusion until discontinuation of dialysis (measured in days)	Up to study participation ends at 1-year follow-up
Donor liver utilization rate		Up to study participation ends at 1-year follow-up
Patient survival rate		30 days, 6 months, 1 year post-transplant
Graft survival rate		30 days, 6 months, 1 year post-transplant
Incidence of adverse events (AEs)		1 year post-transplant
Incidence of serious AEs (SAEs)		1 year post-transplant
Incidence of unanticipated adverse device effects (UADEs)		1 year post-transplant
Incidence of ischemic cholangiopathy		6 months, 1 year post-transplant
Incidence of biopsy-proven liver rejection		6 months, 1 year post-transplant

Collaborators and Investigators

• Sponsor: Bridge to Life Ltd.
• Investigators: Principal Investigator: David Reich, MD, Drexel University

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2021
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): November 30, 2024

Study Registration Dates

• First Submitted: August 31, 2021
• First Submitted That Met QC Criteria: September 14, 2021
• First Posted (Actual): September 16, 2021

Study Record Updates

• Last Update Posted (Actual): May 17, 2023
• Last Update Submitted That Met QC Criteria: May 16, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Liver transplantation; Hypothermic oxygenated machine perfusion; Liver preservation
• Additional Relevant MeSH Terms: Digestive System Diseases; Hepatic Insufficiency; Liver Diseases; End Stage Liver Disease; Liver Failure; Hematinics; Liver Extracts
• Other Study ID Numbers: BTL-2020-01vs

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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