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

NCT ID: NCT05045794

Last Updated: 2024-06-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 219 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-16
• Study Completion Date: 2024-06-10

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.

Conditions

End Stage Liver DIsease; Liver Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Hypothermic oxygenated perfusion (HOPE)

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

Group Type: EXPERIMENTAL

VitaSmart Liver Machine Perfusion System

Intervention Type: DEVICE

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.

Static cold storage

Intervention Type: OTHER

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

Group Type: OTHER

Static cold storage

Intervention Type: OTHER

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

Interventions

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.

Intervention Type: DEVICE

Static cold storage

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

Intervention Type: OTHER

Other Intervention Names

VitaSmart Liver Machine; Hypothermic oxygenated perfusion

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• 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

Exclusion Criteria

• 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

• 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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bridge to Life Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Reich, MD

Role: PRINCIPAL_INVESTIGATOR

Drexel University

Locations

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

Mayo Clinic

Jacksonville, Florida, United States

Cleveland Clinic

Weston, Florida, United States

Indiana University

Indianapolis, Indiana, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Lahey Hospital and Medical Center

Burlington, Massachusetts, United States

Henry Ford Hospital

Detroit, Michigan, United States

Washington University St. Louis

St Louis, Missouri, United States

Nebraska Medical Center

Omaha, Nebraska, United States

Mount Sinai Hospital

New York, New York, United States

Cleveland Clinic

Cleveland, Ohio, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Houston Methodist Hospital

Houston, Texas, United States

University of Wisconsin Madison

Madison, Wisconsin, United States

Countries

United States

References

Kim SC, Foley DP. Strategies to Improve the Utilization and Function of DCD Livers. Transplantation. 2024 Mar 1;108(3):625-633. doi: 10.1097/TP.0000000000004739. Epub 2023 Jul 27.

Reference Type: DERIVED

PMID: 37496117 (View on PubMed)

Other Identifiers

BTL-2020-01vs

Identifier Type: -

Identifier Source: org_study_id