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

Liver Failure Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05045794
• Other study ID #: BTL-2020-01vs
• Status: Completed
• Phase: N/A
• Start date: December 16, 2021
• Est. completion date: June 10, 2024

Study information

• Verified date: June 2024
• Source: Bridge to Life Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 219
• Est. completion date: June 10, 2024
• Est. primary completion date: June 10, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• End Stage Liver DIsease
• Liver Diseases
• Liver Failure

Intervention

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:
• Static cold storage
Donor liver retrieval and preservation using standard of care cold storage methods

Locations

Country	Name	City	State
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	Cleveland Clinic	Cleveland	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	Houston Methodist Hospital	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Mayo Clinic	Jacksonville	Florida
United States	University of Wisconsin Madison	Madison	Wisconsin
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Mount Sinai Hospital	New York	New York
United States	Nebraska Medical Center	Omaha	Nebraska
United States	Washington University St. Louis	Saint Louis	Missouri
United States	Loma Linda University Medical Center	San Bernardino	California
United States	University of California San Francisco	San Francisco	California
United States	Stanford University Medical Center	Stanford	California
United States	Cleveland Clinic	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bridge to Life Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with early allograft dysfunction (EAD)		At Day 7 post-transplant
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Donor liver utilization rate		Up to study participation ends at 1-year follow-up
Secondary	Patient survival rate		30 days, 6 months, 1 year post-transplant
Secondary	Graft survival rate		30 days, 6 months, 1 year post-transplant
Secondary	Incidence of adverse events (AEs)		1 year post-transplant
Secondary	Incidence of serious AEs (SAEs)		1 year post-transplant
Secondary	Incidence of unanticipated adverse device effects (UADEs)		1 year post-transplant
Secondary	Incidence of ischemic cholangiopathy		6 months, 1 year post-transplant
Secondary	Incidence of biopsy-proven liver rejection		6 months, 1 year post-transplant