End Stage Liver Disease, Liver Diseases
Conditions
Keywords
normothermic perfusion, liver transplantation
Brief summary
This trial is to assess the safety and efficacy of normothermic machine perfusion (NMP) as an organ preservation method prior to transplantation using the OrganOx metra™ device.
Detailed description
The standard approach for storage and transportation of livers for transplantation involves cold perfusion with Histidine-tryptophan-ketoglutarate (HTK) or alternative solutions, and storage in sterile bags surrounded by preservation solution in a box by ice. The prolonged cold ischemic injury substantially compounds pre-existing donor liver graft injury, further exacerbating potential risk for recipients. Normothermic perfusion may eliminate cold ischemic injury, and provide a unique opportunity to further assess ex vivo function of the most marginal organs before they are transplanted. Being able to select or eliminate organs in this manner would provide additional livers for transplantation while at the same time minimizing risk for recipients. This non-randomized, open-label, single arm, prospective trial is to assess safety and preliminary efficacy of normothermic machine perfusion on livers accepted under standard and expanded criteria for standard liver transplantation (n=50). Following assessment of donor and recipient eligibility and confirmation of consent, the liver will be preserved on OrganOx metra™ either at the donor hospital or where more practical transported to the University of Alberta hospital with ≤ 6 hours of cold storage and then placed on the metra™ for ≥ 4 hours ('back to base' sub-analysis). At the end of preservation, the liver will be transplanted and the patient managed according to standard local practice and protocols. 100 anonymized patient data from the University of Alberta Hospital Liver Transplant database will be utilized for the matched controls. Enrolled subjects will participate in the study for 30 days (the accrued period to capture primary and secondary end-points: graft and patient survival, graft function, NMP perfusion parameters). Additional routine (non-research) biochemical and survival data will be collected and documented at 3, 6, 9 and 12 months post-transplant. Primary outcomes will be analyzed and reported 30 days following transplantation of the last subject in the study.
Interventions
DEVICEOrganOx metra
Following the routine retrieval procedure at the donor hospital the liver will be flushed with cold preservation solution and prepared for cannulation. The donor organ is then placed on the OrganOx metra device and will be perfused with warmed solution. The OrganOx metra device containing the donor organ is then transported to the recipient transplant centre. The donor liver is then removed from the device and flushed with standard of care preservation solution. Alternatively, where more practical, the livers will be transported to the University of Alberta hospital with ≤ 6 hours of cold storage and then placed on the metra™ for ≥ 4 hours. Implantation and reperfusion of the liver proceed as per the usual practice of the recipient transplant centre.
Sponsors
University of Alberta
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Non-randomized, open-label, single arm, prospective trial using retrospective matched controls
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Recipient inclusion criteria: Adult subjects (age ≥18 years); active on the waiting list for liver transplantation at the University of Alberta Hospital; informed/deferred consent provided. Donor liver inclusion criteria: Whole livers from deceased donors ≥ 40kg in weight, that are deemed suitable for transplantation as per local and international practice, and at the discretion of the transplanting surgeon. Donor livers will be placed on the metra™ device either at the donor hospital, or where more practical, transported to the University of Alberta hospital with ≤ 6 hours of cold storage and then reperfused on metra™ for ≥ 4 hours ('back-to-base' sub-analysis). Expanded criteria grafts may include, but not be restricted to the following graft qualities. Such grafts will only be transplanted at the recipient transplant surgeon's discretion, if judged to be safe and appropriate for that individual recipient. Donation after Neurological Determination of Death (NDD) Expanded Criteria livers may include: ≥60% macro/micro steatosis; cold ischemia \> 10 hours; combined steatosis 30-60% and \>6hr cold storage; significant liver trauma. Donation after Cardio-Circulatory Death (DCD) Expanded Criteria livers may include: Age up to 75; mild steatosis (30%); DCD offers from distant centres; warm time up to 60 min. As per standard clinical practice, the on-call recipient transplant surgeon will evaluate donor and graft information, weigh the risks and benefits of graft utilization for a particular recipient, and make the final decision about whether or not to proceed to transplantation. Based on preliminary experience with the metraTM, perfusion parameters may additionally be considered in reaching a decision: * Normal, stable portal vein flow (≥800-1000ml/minute) and artery flow (≥200ml/minute) * Falling lactate levels * Stable perfusate pH within the normal range (7.2 - 7.4) after bicarbonate correction * Evenly perfused graft on the device
Exclusion criteria
Recipient
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Graft survival rate | Day 30 | Graft survival rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Early Allograft Dysfunction (EAD) rate | Up to Day 7 | EAD rate |
| Daily lactate levels | Up to Day 7 | Daily lactate levels in the blood |
| Perfusate AST levels | Day -1 and Day 0 | AST levels in perfusate blood |
| Patient survival rate | Day 30 | Patient survival rate |
| Perfusate alanine transaminase (ALT) levels | Day -1 and Day 0 | ALT levels in perfusate blood |
| Perfusate bilirubin levels | Day -1 and Day 0 | Bilirubin levels in perfusate blood |
| Perfusate lactate levels | Day -1 and Day 0 | Lactate levels in perfusate blood |
| Peak aspartate transaminase (AST) levels | Up to Day 7 | Peak AST levels in the blood |
Countries
Canada
Outcome results
None listed