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

Multicenter, Prospective, Open-label, Randomized Controlled Clinical Trial to Compare the Safety & 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.

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.

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