Safety and Feasibility of Normothermic Machine Perfusion to Preserve and Evaluate Orphan Livers

Pilot Study to Assess Safety and Feasibility of Normothermic Machine Perfusion to Preserve and Evaluate Orphan Livers

Orphan livers are organs that have been declined for clinical use by all centers due to their marginality. The current standard of care of liver preservation before transplant is cold storage. NMP may allow these livers to be evaluated before transplantation. NMP has already been used in a clinical setting with promising results. The advantage to utilizing NMP is that it would attenuate the incidence and clinical impact of classical preservation injury, allow liver function assessment before implantation and thus improve donor pool and outcomes for high risk ECD liver transplants performed at our center.

Study Overview

• Status: Active, not recruiting
• Conditions: Liver Transplantation
• Intervention / Treatment: Device: Normothermic Liver perfusion

Detailed Description

This will be a single center prospective cohort pilot study. 30 livers that have been declined for clinical use by all centers due to their marginality will be preserved with NMP in 1-18 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. Once the liver grafts have been evaluated and determined to be transplantable, 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 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 (Anticipated): 30
• 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 to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

Recipient 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

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: Normothermic Liver perfusion; This group has the liver grafts preserved using the Normothermic Liver perfusion Device	Device: Normothermic Liver perfusion; The liver grafts will be preserved and evaluated at physiological temperature and have continuous perfusion with oxygen and nutrient supply in the ex vivo organ preservation phase

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of patient survival		30 days post-transplantation
The rate of primary non-function	primary non-function is defined as non life sustaining liver function requiring retransplantation or leading to death with 30 days after transplantation	30 days post-transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
graft survival	The allograft will be considered lost if a patient has a liver re-transplant or in the event of patient death.	6 months post-transplantation
The rate of Early Allograft Dysfunction post-transplantation	The presence of at least one of the following at post-transplant 7 days: serum bilirubin >= 10 mg/dL, international normalized ratio (INF) >= 1.6; and/or aspartate aminotransferase (AST) > 2000 U/L at any time in the first 7 posttransplant days (POD)	7 days post-transplantation
peak aspartate aminotransferase (AST) in the first 7 days post-transplantation	CLINICAL LABORATORY TEST	in the first 7 days post-transplantation
peak Alanine Aminotransferase (ALT) in the first 7 days post-transplantation	CLINICAL LABORATORY TEST	in the first 7 days post-transplantation
peak bilirubin in the first 7 days post-transplantation	CLINICAL LABORATORY TEST	in the first 7 days post-transplantation

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2020
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: February 15, 2018
• First Submitted That Met QC Criteria: February 28, 2018
• First Posted (Actual): March 7, 2018

Study Record Updates

• Last Update Posted (Actual): April 13, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: Orphan liver

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