Liver Transplant
Conditions
Brief summary
Prospective, randomized, controlled clinical trial to determine the overall efficacy of normothermic machine perfusion (NMP) for steatotic liver preservation versus traditional static cold storage (SCS), in 50 liver transplant recipients with 1-year follow-up.
Detailed description
This is a prospective, randomized, controlled clinical trial comparing static cold storage (SCS) versus normothermic machine perfusion (NMP) for organ preservation before liver transplantation with steatotic livers (between 30 % and 60% of histologic macrovesicular steatosis), in order to: Main Objective: To compare the effect of NMP versus SCS in preventing preservation injury and graft dysfunction, as measured by highest transaminase levels during the first week after liver transplantation. Secondary Objectives: * To compare graft and patient survival between the NMP and SCS steatotic livers. * To compare the liver biochemical function between the NMP and SCS steatotic livers. * To compare the physiological response to the reperfusion between the NMP and SCS steatotic livers. * To compare the evidence of reperfusion injury between the NMP and SCS steatotic livers. * To compare the evidence of ischemic cholangiopathy between the NMP and SCS steatotic livers.
Interventions
PROCEDUREStatic cold storage (SCS)
The liver is flushed and cooled with specialist preservation fluid, then stored in an icebox.
During NMP, the liver is perfused with oxygenated blood, medications and nutrients at normal body temperature to maintain a physiological milieu.
Sponsors
Instituto de Investigacion Sanitaria La Fe
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
LIVER DONOR: * Donors older than 16 years * Liver donation grafts due to brain death * Steatosis confirmed by histological study (between 30% and 60% of macrovesicular steatosis) LIVER RECIPIENT: * Adult patients (18 years or older) * Active liver transplant waiting list candidate * Able to give informed consent
Exclusion criteria
LIVER DONOR: * Living donors * Liver destined to the transplant split * Donor age \<16 years * Donation after death due to asystole. * When the biopsy establishes a steatosis ≥ 50%, patients who fulfill at least 3 of the following 5 risk factors will be excluded: Transaminases (AST and ALT) ≥ 200 U / L; Age ≥ 55 years; Hypernatremia ≥ 155 mEq / L; Cardiovascular risk factors, at least 2 of the following 5: DM, HTA, IMC ≥ 35, Active smoking, ischemic stroke; Days of stay in ICU ≥ 4 days with vasoactive drugs (noradrenaline or dobutamine at any dose) LIVER RECIPIENT: * Age under 18 * Acute/fulminant hepatic failure * Transplant of more than one organ (for example, liver and kidney) * Rejection of informed consent * Unable to give informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Peak of transaminases (AST and ALT) | Day 1 post-transplant. |
| Peak of transaminases (AST and ALT) l | Day 7 post-transplant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient survival | Day 30 post-transplant, month 6 post-transplant, month 12 post-transplant. | — |
| Post-reperfusion syndrome, measured by mean arterial pressure (MAP) levels | During the first 5 minutes after reperfusion | Post-reperfusion syndrome is defined as a decrease in mean arterial pressure (MAP) of more than 30% of the baseline value for more than one minute during the first five minutes after reperfusion. This will be evaluated in the context of the use of vasopressors. |
| Biochemical function of the liver measured by Bilirubin post-transplant levels | Day 1, day 3, day 5, day 7, day 30, month 6, month 12 post- transplant | — |
| Biochemical function of the liver measured by GGT post-transplant levels | Day 1, day 3, day 5, day 7, day 30, month 6, month 12 post- transplant | — |
| Biochemical function of the liver measured by AST post-transplant levels | Day 1, day 3, day 5, day 7, day 30, month 6, month 12 post- transplant | — |
| Biochemical function of the liver measured by ALT post-transplant levels | Day 1, day 3, day 5, day 7, day 30, month 6, month 12 post- transplant | — |
| Biochemical function of the liver measured by INR post-transplant levels | Day 1, day 3, day 5, day 7, day 30, month 6, month 12 post- transplant | — |
| Primary graft failure | Day 10 post-transplant. | Primary graft failure: irreversible graft dysfunction that requires emergency hepatic replacement during the first 10 days after liver transplantation, in the absence of technical or immunological causes. |
| Intensive care stay duration | Day 30 | — |
| Hospital stay duration | Day 30 | — |
| Renal replacement therapy need | Day 30, month 6, month 12 post- transplant | — |
| Intraoperative thromboelastogram result | In transplant surgery | — |
| Histological evidence of reperfusion injury | In transplant surgery | Post-reperfusion biopsies will be compared with baseline pre-reperfusion biopsies and classified according to standard histological criteria (blind comparison to third parties). |
| Evidence of biliary stenosis in magnetic resonance cholangiography (MRS). | 6 months after transplantation. | — |
| Early graft dysfunction | 7 days post-transplant | Defined by: 1. Bilirubin \> 10 mg / dl daily 7 after transplant 2. INR \> 1.6 on day 7 after transplantation. 3. Peak AST and ALT \> 2000 IU / L in the first 7 days after transplantation |
| Graft survival | Day 30 post-transplant, month 6 post-transplant, month 12 post-transplant. | — |
Countries
Spain
Outcome results
None listed