Sequential Hypo- and Normo-thermic Perfusion to Preserve Extended Criteria Donor Livers for Transplantation

Assess Safety and Feasibility of Sequential Hypothermic Oxygenated Machine Perfusion and Normothermic Machine Perfusion to Preserve Extended Criteria Donor Livers for Transplantation

Hypothermic machine perfusion (HMP) has been shown to be beneficial to preserve extended criteria donor (ECD) livers for transplantation. Normothermic machine perfusion (NMP) had the same benefits and also the convenience on liver quality assessment. The investigators proposed to do sequential HMP (1-4 hours) and NMP (1-14 hours) on 18 ECD transplanted human livers by using an institutional-developed perfusion device for liver transplantation.

Study Overview

• Status: Active, not recruiting
• Conditions: Liver Transplantation
• Intervention / Treatment: Device: Liver Machine Perfusion (MP) device

Detailed Description

Liver transplantation is a successful therapy on the patients with end-stage liver disease, however is limited by the shortage of donor organs. Donor criteria were expanded in the past decades, however the extended criteria donor (ECD) livers may induce a higher risk of complications. Static cold storage (SCS) is the standard procedure for ex vivo liver preservation for about 4 decades, but has the limitation on preserving ECD livers and especially the inconvenience to evaluate liver quality prior to transplantation. Hypothermic (4-8 Celsius degree) machine perfusion (HMP) and Normothermic (35-37 Celsius degree) machine perfusion (NMP) have been shown to be beneficial to preserve extended criteria donor (ECD) livers respectively. NMP also had the convenience on liver quality assessment. The investigators had an institutional-developed device for liver NMP used on 25 patients with the FDA's IDE approval. In the present study the investigators are proposing to expand the use of the device on sequential HMP (1-4 hours) and NMP (1-14 hours) on 18 ECD transplanted human livers. This will be a single center prospective pilot study. The liver metabolism and hydrodynamics during perfusion will be recorded. The transplant procedure and post-transplant care will follow the clinical standard of care. The follow-up period is 12 months after transplantation. The primary end point will be the rate of patient survival and primary non function (PNF) within 30 days after transplantation, while the secondary end points will be: Early Allograft Dysfunction (EAD), 6 months patient and graft survival, peak liver function tests in the first 7 days after transplantation, 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).

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients undergoing liver transplantation
• Age 18 or older at the time of transplantation
• Willingness and ability to comply with the study procedures
• Signed Informed Consent Form

Exclusion Criteria:

• Recipient of partial grafts (split and living donors)
• Mentally or legally incapacitated subjects
• Inability to understand the procedures due to language barriers
• Multiorgan transplant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liver perfusion; Device: Liver Machine Perfusion (MP) Device The liver grafts will be preserved at hypothermic and normothermic temperature on the institutional-developed Liver MP Device, and have continuous perfusion with oxygen supply in the ex vivo organ preservation phase.	Device: Liver Machine Perfusion (MP) device; Donor livers will have ex vivo continuous perfusion on the institutional-developed Liver MP device. The temperature of liver grafts will be controlled during perfusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
patient survival at 1 month post-transplant	Patient survival will be recorded at 1 month post transplantation.	1 month post-transplant
graft survival at 1 month post-transplant	graft survival will be recorded at 1 month post transplantation. The allograft will be considered lost if a patient has a primary non function (PNF), liver re-transplant or in the event of patient death.	1 month post-transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rate of post-transplant early allograft dysfunction (EAD)	EAD is defined as the presence of one or more of the following previously defined postoperative laboratory analyses reflective of liver injury and function: bilirubin ≥10mg/dL on post-operative day (POD) 7, international normalized ratio (INR) ≥1.6 on POD 7, and alanine or aspartate aminotransferases (ALT or AST) >2000 IU/L within the first 7 days.	in the first 7 days after transplantation
patient survival at 6 month post-transplant	patient survival will be recorded at 6 months post transplantation.	6 month post-transplant
graft survival at 6 month post-transplant	graft survival will be recorded at 6 month post transplantation. The allograft will be considered lost if a patient has a primary non function (PNF), liver re-transplant or in the event of patient death.	6 month post-transplant
Estimated blood loss at transplant surgery	Estimated blood loss (ml) during transplant surgery	during surgery
peak alanine aminotransferases in the first 7 days after transplantation	peak level (U/L) of alanine aminotransferases in the first 7 days after transplantation	in the first 7 days after transplantation
peak aspartate aminotransferases in the first 7 days after transplantation	peak level (U/L) of aspartate aminotransferases in the first 7 days after transplantation	in the first 7 days after transplantation
total bilirubin on post-operative day 7	total bilirubin (mg/dL) on post-operative day 7	on post-operative day 7
international normalized ratio on post-operative day 7	international normalized ratio on post-operative day 7	on post-operative day 7
Hospital length of stay	Length of stay (days) in the hospital at the time for transplantation	up to 36 weeks
ICU length of stay	Length of stay (days) in ICU at the time after liver transplantation	up to 36weeks

Collaborators and Investigators

• Sponsor: Koji Hashimoto
• Investigators: Principal Investigator: Koji Hashimoto, MD, PhD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2021
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 30, 2027

Study Registration Dates

• First Submitted: July 10, 2019
• First Submitted That Met QC Criteria: July 15, 2019
• First Posted (Actual): July 18, 2019

Study Record Updates

• Last Update Posted (Actual): July 26, 2024
• Last Update Submitted That Met QC Criteria: July 25, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: Sequential perfusion

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes