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

Primary Purpose

End Stage Liver DIsease, Liver Failure

Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
VitaSmart Liver Machine Perfusion System
Static cold storage
Sponsored by
Bridge to Life Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for End Stage Liver DIsease focused on measuring Hypothermic oxygenated machine perfusion, Liver preservation, Liver transplantation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Loma Linda University Medical Center
  • University of California San Francisco
  • Stanford University Medical Center
  • Mayo Clinic
  • Cleveland Clinic
  • Indiana University
  • Ochsner Clinic Foundation
  • Lahey Hospital and Medical Center
  • Henry Ford Hospital
  • Washington University St. Louis
  • Nebraska Medical Center
  • Mount Sinai Hospital
  • Cleveland Clinic
  • Vanderbilt University Medical Center
  • Houston Methodist Hospital
  • University of Wisconsin Madison

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Hypothermic oxygenated perfusion (HOPE)

Static cold storage

Arm Description

Ex-vivo donor liver preservation using static cold storage followed by HOPE using the VitaSmart Liver Machine

Ex-vivo donor liver preservation using static cold storage only

Outcomes

Primary Outcome Measures

Proportion of patients with early allograft dysfunction (EAD)

Secondary Outcome Measures

Model for early allograft function (MEAF) score
Based on definition by Olthoff et al, 2010 (doi: 10.1002/lt.22091)
Proportion of patients with primary non-function (PNF)
Based on definition by Pareja et al, 2015 (doi: 10.1002/lt.23990)
Length of hospital stay
Duration from initial ICU admission to hospital discharge order (measured in days)
Length of intensive care unit stay
Duration from initial ICU admission to ICU discharge order (measured in days)
Duration on dialysis
Duration from establishment of graft reperfusion until discontinuation of dialysis (measured in days)
Donor liver utilization rate
Patient survival rate
Graft survival rate
Incidence of adverse events (AEs)
Incidence of serious AEs (SAEs)
Incidence of unanticipated adverse device effects (UADEs)
Incidence of ischemic cholangiopathy
Incidence of biopsy-proven liver rejection

Full Information

First Posted
August 31, 2021
Last Updated
May 16, 2023
Sponsor
Bridge to Life Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05045794
Brief Title
Bridge to HOPE: Hypothermic Oxygenated Perfusion Versus Cold Storage Prior to Liver Transplantation
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 16, 2021 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
November 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bridge to Life Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End Stage Liver DIsease, Liver Failure
Keywords
Hypothermic oxygenated machine perfusion, Liver preservation, Liver transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
This is a randomized, controlled, open-label, sequential assignment, non-inferiority design comparing two treatment arms (HOPE, static cold storage)
Masking
None (Open Label)
Masking Description
A centralized radiologist who evaluates imaging (MRCP) for one of the secondary endpoints (ischemic cholangiopathy) will be blinded to treatment assignment. The study is otherwise open label.
Allocation
Randomized
Enrollment
244 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Hypothermic oxygenated perfusion (HOPE)
Arm Type
Experimental
Arm Description
Ex-vivo donor liver preservation using static cold storage followed by HOPE using the VitaSmart Liver Machine
Arm Title
Static cold storage
Arm Type
Other
Arm Description
Ex-vivo donor liver preservation using static cold storage only
Intervention Type
Device
Intervention Name(s)
VitaSmart Liver Machine Perfusion System
Other Intervention Name(s)
VitaSmart Liver Machine, Hypothermic oxygenated perfusion
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Static cold storage
Intervention Description
Donor liver retrieval and preservation using standard of care cold storage methods
Primary Outcome Measure Information:
Title
Proportion of patients with early allograft dysfunction (EAD)
Time Frame
At Day 7 post-transplant
Secondary Outcome Measure Information:
Title
Model for early allograft function (MEAF) score
Description
Based on definition by Olthoff et al, 2010 (doi: 10.1002/lt.22091)
Time Frame
Within 3 days post-transplant
Title
Proportion of patients with primary non-function (PNF)
Description
Based on definition by Pareja et al, 2015 (doi: 10.1002/lt.23990)
Time Frame
Within 7 days post-transplant
Title
Length of hospital stay
Description
Duration from initial ICU admission to hospital discharge order (measured in days)
Time Frame
Up to study participation ends at 1-year follow-up
Title
Length of intensive care unit stay
Description
Duration from initial ICU admission to ICU discharge order (measured in days)
Time Frame
Up to study participation ends at 1-year follow-up
Title
Duration on dialysis
Description
Duration from establishment of graft reperfusion until discontinuation of dialysis (measured in days)
Time Frame
Up to study participation ends at 1-year follow-up
Title
Donor liver utilization rate
Time Frame
Up to study participation ends at 1-year follow-up
Title
Patient survival rate
Time Frame
30 days, 6 months, 1 year post-transplant
Title
Graft survival rate
Time Frame
30 days, 6 months, 1 year post-transplant
Title
Incidence of adverse events (AEs)
Time Frame
1 year post-transplant
Title
Incidence of serious AEs (SAEs)
Time Frame
1 year post-transplant
Title
Incidence of unanticipated adverse device effects (UADEs)
Time Frame
1 year post-transplant
Title
Incidence of ischemic cholangiopathy
Time Frame
6 months, 1 year post-transplant
Title
Incidence of biopsy-proven liver rejection
Time Frame
6 months, 1 year post-transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Reich, MD
Organizational Affiliation
Drexel University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Loma Linda University Medical Center
City
San Bernardino
State/Province
California
ZIP/Postal Code
92408
Country
United States
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Stanford University Medical Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Mayo Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Cleveland Clinic
City
Weston
State/Province
Florida
ZIP/Postal Code
33331
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Ochsner Clinic Foundation
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Lahey Hospital and Medical Center
City
Burlington
State/Province
Massachusetts
ZIP/Postal Code
01895
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Washington University St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Mount Sinai Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Houston Methodist Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Wisconsin Madison
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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