Sequential Hypo- and Normo-thermic Perfusion to Preserve Extended Criteria Donor Livers for Transplantation
Study Details
Study Description
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 15 ECD human livers by using an institutional-developed perfusion device for liver transplantation.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
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 15 ECD 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 Design
Arms and Interventions
| 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.
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Outcome Measures
Primary Outcome Measures
- patient survival at 1 month post-transplant [1 month post-transplant]
Patient survival will be recorded at 1 month post transplantation.
- graft survival at 1 month post-transplant [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.
Secondary Outcome Measures
- rate of post-transplant early allograft dysfunction (EAD) [in the first 7 days after transplantation]
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.
- patient survival at 6 month post-transplant [6 month post-transplant]
patient survival will be recorded at 6 months post transplantation.
- graft survival at 6 month post-transplant [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.
- Estimated blood loss at transplant surgery [during surgery]
Estimated blood loss (ml) during transplant surgery
- peak alanine aminotransferases in the first 7 days after transplantation [in the first 7 days after transplantation]
peak level (U/L) of alanine aminotransferases in the first 7 days after transplantation
- peak aspartate aminotransferases in the first 7 days after transplantation [in the first 7 days after transplantation]
peak level (U/L) of aspartate aminotransferases in the first 7 days after transplantation
- total bilirubin on post-operative day 7 [on post-operative day 7]
total bilirubin (mg/dL) on post-operative day 7
- international normalized ratio on post-operative day 7 [on post-operative day 7]
international normalized ratio on post-operative day 7
- Hospital length of stay [up to 36 weeks]
Length of stay (days) in the hospital at the time for transplantation
- ICU length of stay [up to 36weeks]
Length of stay (days) in ICU at the time after liver transplantation
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients undergoing liver transplantation
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Age 18 or older at the time of transplantation
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Willingness and ability to comply with the study procedures
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Signed Informed Consent Form
Exclusion Criteria:
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Recipient of partial grafts (split and living donors)
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Mentally or legally incapacitated subjects
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Inability to understand the procedures due to language barriers
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Multiorgan transplant
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cleveland Clinic | Cleveland | Ohio | United States | 44195 |
Sponsors and Collaborators
- The Cleveland Clinic
Investigators
- Principal Investigator: Cristiano Quintini, MD, The Cleveland Clinic
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Sequential perfusion