Clinical trial NCT04023773: Sequential Hypo- and Normo-thermic Perfusion to Preserve Extended Criteria Donor Livers for Transplantation
Official title: Assess Safety and Feasibility of Sequential Hypothermic Oxygenated Machine Perfusion and Normothermic Machine Perfusion to Preserve Extended Criteria Donor Livers for Transplantation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Liver Transplantation
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2019-07-18
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Eighteen extended criteria donor livers will be transplanted after receiving sequential hypothermic and normothermic machine perfusion preservation prior to transplantation.
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: patient survival at 1 month post-transplant
timeFrame: 1 month post-transplant
measure: graft survival at 1 month post-transplant
timeFrame: 1 month post-transplant
Secondary outcomes:
measure: rate of post-transplant early allograft dysfunction (EAD)
timeFrame: in the first 7 days after transplantation
measure: patient survival at 6 month post-transplant
timeFrame: 6 month post-transplant
measure: graft survival at 6 month post-transplant
timeFrame: 6 month post-transplant
measure: Estimated blood loss at transplant surgery
timeFrame: during surgery
measure: peak alanine aminotransferases in the first 7 days after transplantation
timeFrame: in the first 7 days after transplantation
measure: peak aspartate aminotransferases in the first 7 days after transplantation
timeFrame: in the first 7 days after transplantation
measure: total bilirubin on post-operative day 7
timeFrame: on post-operative day 7
measure: international normalized ratio on post-operative day 7
timeFrame: on post-operative day 7
measure: Hospital length of stay
timeFrame: up to 36 weeks
measure: ICU length of stay
timeFrame: up to 36weeks
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Koji Hashimoto, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: