Pilot Study to Assess Safety and Feasibility of Normothermic Machine Preservation In Human Liver Transplantation

NCT ID: NCT02515708

Last Updated: 2020-10-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-16
• Study Completion Date: 2020-06-09

Brief Summary

Normothermic machine perfusion (NMP) preservation is a promising method to decrease the complication of marginal donor livers compared to cold storage (CS). The aim of this project is to assess safety and feasibility of NMP in human liver transplantation. This will be a single center prospective cohort pilot study. Thirty-two livers with acceptable quality for transplantation will be preserved with NMP in 2-18 hours and transplanted. The follow-up period will be 6 months post-transplantation. The outcome will be compared to 100 historical patients transplanted in our program in the past 5 years (liver preserved using CS) with matched characteristics on age, Model for End-Stage Liver Disease (MELD) score, preservation time, etc.

Detailed Description

The shortage of donor organs leads to the use of marginal donors including donors after cardiac death. Normothermic machine perfusion (NMP) preservation is a promising method to decrease their high risk of complication compared to the standard cold storage (CS). The aim of this project is to assess safety and feasibility of NMP in human liver transplantation.

This will be a single center prospective cohort pilot study. Thirty-two livers that have acceptable quality for transplantation will be preserved with NMP in 2-18 hours after cross clamp and cold flush. The liver grafts at NMP will be at physiological temperature and have oxygen and nutrient supply with continuous perfusion. The transplantation and post-transplant care will follow the standard of care. The follow-up period is 12 months after transplantation. The primary end point will be the rate of post-transplant Early Allograft Dysfunction (EAD), while the secondary end points will be: primary non function (PNF) rate, 1 and 6 months patient and graft survival, peak liver function tests in the first 7 days after transplantation, intraoperative hepatic arterial and portal flow measurement, rate and magnitude of post-reperfusion syndrome, surgical outcomes (operative time, transfusion requirement etc.), rate of post-transplant kidney failure, assessment of histological ischemia reperfusion (liver and bile duct), rate of vascular complications, rate of biliary complications, hospital and ICU length of stay, rejection rate, infection rate, the ability to predict function based on "on-pump" viability markers, and the incidence of adverse effect (AE).

The outcome will be compared to a control group of 100 historical patients (matched with a 1:4 ratio) transplanted in our program in the past 10 years (liver preserved using CS). Control subjects will be matched using donor and recipient age, Model for End-Stage Liver Disease (MELD) score, cold ischemia time, donor risk index and presence of steatosis.

Conditions

Liver Transplantation

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Normothermic Liver perfusion

This group has the liver grafts preserved using the Normothermic Liver perfusion Device.

Group Type: EXPERIMENTAL

Normothermic Liver perfusion Device

Intervention Type: DEVICE

The liver grafts will be preserved at physiological temperature and have continuous perfusion with oxygen and nutrient supply in the ex vivo organ preservation phase.

Normothermic Machine Perfusion (single pump)

This group has the liver grafts preserved using a single-pump variant of the Normothermic Liver perfusion Device.

Group Type: OTHER

Normothermic Liver perfusion Device

Intervention Type: DEVICE

The liver grafts will be preserved at physiological temperature and have continuous perfusion with oxygen and nutrient supply in the ex vivo organ preservation phase.

Interventions

Normothermic Liver perfusion Device

The liver grafts will be preserved at physiological temperature and have continuous perfusion with oxygen and nutrient supply in the ex vivo organ preservation phase.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Patients undergoing primary liver transplantation
• Age 18-75 years at the time of transplantation
• Willingness and ability to comply with the study procedures
• Signed Informed Consent Form
• For patients with hepatocellular carcinoma as indication for Orthoptic Liver Transplantation (OLT), tumor must be within Milan Criteria or down-staged to Milan Criteria.

Exclusion Criteria

• History of prior solid organ transplantation
• Patient on a respiratory and/or cardiocirculatory support at the time of transplant
• MELD score >35
• HIV positive patient
• Patient with current severe systemic infection
• Multiorgan transplant

• Donor age <14 or >70 years
• Liver steatosis (on visual estimate or on liver biopsy) > 30%
• Donors with Grade 2-3 traumatic liver laceration
• Partial grafts (living donors and split liver donors)
• Liver in which the investigator is unwilling or unable (for logistical reasons) to perform normothermic machine perfusion (NMP) preservation
• Inability to NMP perfuse the liver within 4 hours after cross clamp

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cristiano Quintini

OTHER

Sponsor Role: lead

Responsible Party

Cristiano Quintini

Sponsor-Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Cristiano Quintini, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

Cleveland Clinic

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

15-549

Identifier Type: -

Identifier Source: org_study_id