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

• ClinicalTrials.gov Identifier: NCT05045794
• Recruitment Status: Active, not recruiting
• First Posted: September 16, 2021
• Last Update Posted: May 17, 2023
• Sponsor: Bridge to Life Ltd.
• Information provided by (Responsible Party): Bridge to Life Ltd.

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.

Condition or disease	Intervention/treatment	Phase
End Stage Liver DIsease; Liver Failure	Device: VitaSmart Liver Machine Perfusion System; Other: Static cold storage	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 244 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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.
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: December 16, 2021
• Estimated Primary Completion Date: December 31, 2023
• Estimated Study Completion Date: November 30, 2024

Arms and Interventions

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
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

Outcome Measures

Primary Outcome Measures :

1. Proportion of patients with early allograft dysfunction (EAD) [ Time Frame: At Day 7 post-transplant ]

Secondary Outcome Measures :

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

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, California

Loma Linda University Medical Center

San Bernardino, California, United States, 92408

University of California San Francisco

San Francisco, California, United States, 94143

Stanford University Medical Center

Stanford, California, United States, 94305

United States, Florida

Mayo Clinic

Jacksonville, Florida, United States, 32224

Cleveland Clinic

Weston, Florida, United States, 33331

United States, Indiana

Indiana University

Indianapolis, Indiana, United States, 46202

United States, Louisiana

Ochsner Clinic Foundation

New Orleans, Louisiana, United States, 70121

United States, Massachusetts

Lahey Hospital and Medical Center

Burlington, Massachusetts, United States, 01895

United States, Michigan

Henry Ford Hospital

Detroit, Michigan, United States, 48202

United States, Missouri

Washington University St. Louis

Saint Louis, Missouri, United States, 63110

United States, Nebraska

Nebraska Medical Center

Omaha, Nebraska, United States, 68198

United States, New York

Mount Sinai Hospital

New York, New York, United States, 10029

United States, Ohio

Cleveland Clinic

Cleveland, Ohio, United States, 44195

United States, Tennessee

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37232

United States, Texas

Houston Methodist Hospital

Houston, Texas, United States, 77030

United States, Wisconsin

University of Wisconsin Madison

Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

Bridge to Life Ltd.

Investigators

• Principal Investigator: David Reich, MD; Drexel University

More Information

• Responsible Party: Bridge to Life Ltd.
• ClinicalTrials.gov Identifier: NCT05045794
• Other Study ID Numbers: BTL-2020-01vs
• First Posted: September 16, 2021
• Last Update Posted: May 17, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Bridge to Life Ltd.:

Hypothermic oxygenated machine perfusion; Liver preservation; Liver transplantation

Additional relevant MeSH terms:

Liver Diseases; Liver Failure; End Stage Liver Disease; Digestive System Diseases; Hepatic Insufficiency; Liver Extracts; Hematinics