Clinical trial NCT02515708: Pilot Study to Assess Safety and Feasibility of Normothermic Machine Preservation In Human Liver Transplantation
Official title: A Phase I Pilot Study to Assess Safety and Feasibility of Normothermic Machine Preservation In Human Liver Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Liver Transplantation
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2015-08-05
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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:

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

Donor Exclusion Criteria:

* 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

Primary outcomes:
measure: the rate of Early Allograft Dysfunction post-transplantation in Normothermically Machine Perfused (NMP) livers
timeFrame: 7 days post-transplantation
Secondary outcomes:
measure: primary non-function rate
timeFrame: in the first 10 days post-transplantation
measure: graft survival
timeFrame: 6 months post-transplantation
measure: peak liver function tests in the first 7 days post-transplantation
timeFrame: in the first 7 days post-transplantation
measure: intraoperative flow measurement
timeFrame: intraoperative
measure: post reperfusion syndrome (composite)
timeFrame: in the first 7 days post-transplantation
measure: surgical outcomes (composite)
timeFrame: intraoperative
measure: rate of post-transplant kidney failure
timeFrame: in the 1, 3, 6 ,9 months post-transplantation
measure: histology of liver parenchyma
timeFrame: On the day of transplantation
measure: vascular complications rate
timeFrame: in the first day post-transplantation
measure: biliary complications rate
timeFrame: 6 months post-transplantation
measure: hospital and ICU length of stay (composite)
timeFrame: 6 months post-transplantation
measure: rejection rate
timeFrame: 6 months post-transplantation
measure: opportunistic viral infection rate
timeFrame: 6 months post-transplantation
measure: patient survival
timeFrame: 6 months post-transplantation
measure: histology of bile duct
timeFrame: On the day of transplantation
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Cristiano Quintini, MD
role: PRINCIPAL_INVESTIGATOR
References: