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Efficacy of Ex-situ Normothermic Perfusion Versus Cold Storage in the Transplant With Steatotic Liver Graft.

  • Clinicaltrials.gov identifier

    NCT03930459

  • Recruitment Status

    Recruiting

  • First Posted

    April 29, 2019

  • Last update posted

    August 6, 2019

Study Description

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.

  • Condition or Disease:Liver Transplant
  • Intervention/Treatment: Procedure: Static cold storage (SCS)
    Device: Normothermic machine perfusion (NMP)
  • Phase: N/A

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.

Study Design

  • Study Type: Interventional
  • Estimated Enrollment: 50 participants
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Prevention
  • Official Title: Clinical Trial to Compare the Efficacy of Ex-situ Normothermic Perfusion With Cold Storage in the Transplant With Steatotic Liver Graft.
  • Actual Study Start Date: April 2019
  • Estimated Primary Completion Date: March 2023
  • Estimated Study Completion Date: March 2023

Arms and interventions

Arm Intervention/treatment
Experimental: Static cold storage (SCS)
Traditional method of organ preservation which involves flushing of cold preservation solution following complete dissection and interruption of blood supply to the donor organ. Although cold preservation slows metabolism by 10- to 12-fold, substantial anaerobic activity continues even at ice temperature. This lead to the generation of reactive oxygen species that are the basis of ischaemia-reperfusion injury, when the organ is re-exposed to oxygenated blood at the time of transplantation. This damage, exacerbated by any prior injury, limits the maximum safe preservation time of the donor organ.
Procedure: Static cold storage (SCS)
The liver is flushed and cooled with specialist preservation fluid, then stored in an icebox.
Experimental: Normothermic machine perfusion (NMP)
The main goal of NMP is to optimize graft preservation by mimicking physiological conditions. The perfused organ is supplied with nutrients and oxygen to maintain metabolic hemostasis. Under these conditions, ATP and glycogen reserves can be maintained or actively restored. At the same time, toxic products from the cellular milieu are continuously eliminated, so the cell-mediated injury phase of reperfusion injury can be minimized. Thus, ischemic injury is avoided and the activation of cell death cascades is prevented. This allows both hepatocellular and biliary protection.
Device: Normothermic machine perfusion (NMP)
During NMP, the liver is perfused with oxygenated blood, medications and nutrients at normal body temperature to maintain a physiological milieu.

Outcome Measures

  • Primary Outcome Measures: 1. Peak of transaminases (AST and ALT) [ Time Frame: Day 3 post-transplant. ]
  • 2. Peak of transaminases (AST and ALT) [ Time Frame: Day 5 post-transplant. ]
  • 3. Peak of transaminases (AST and ALT) l [ Time Frame: Day 7 post-transplant. ]
  • 4. Peak of transaminases (AST and ALT) [ Time Frame: Day 1 post-transplant. ]
  • Secondary Outcome Measures: 1. Primary graft failure [ Time Frame: 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.
  • 2. Graft survival [ Time Frame: Day 30 post-transplant, month 6 post-transplant, month 12 post-transplant. ]
  • 3. Patient survival [ Time Frame: Day 30 post-transplant, month 6 post-transplant, month 12 post-transplant. ]
  • 4. Post-reperfusion syndrome, measured by mean arterial pressure (MAP) levels [ Time Frame: 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.
  • 5. Biochemical function of the liver measured by Bilirubin post-transplant levels [ Time Frame: Day 1, day 3, day 5, day 7, day 30, month 6, month 12 post- transplant ]
  • 6. Biochemical function of the liver measured by GGT post-transplant levels [ Time Frame: Day 1, day 3, day 5, day 7, day 30, month 6, month 12 post- transplant ]
  • 7. Biochemical function of the liver measured by AST post-transplant levels [ Time Frame: Day 1, day 3, day 5, day 7, day 30, month 6, month 12 post- transplant ]
  • 8. Biochemical function of the liver measured by ALT post-transplant levels [ Time Frame: Day 1, day 3, day 5, day 7, day 30, month 6, month 12 post- transplant ]
  • 9. Biochemical function of the liver measured by INR post-transplant levels [ Time Frame: Day 1, day 3, day 5, day 7, day 30, month 6, month 12 post- transplant ]
  • 10. Early graft dysfunction [ Time Frame: 7 days post-transplant ]
    Defined by: Bilirubin > 10 mg / dl daily 7 after transplant INR > 1.6 on day 7 after transplantation. Peak AST and ALT > 2000 IU / L in the first 7 days after transplantation
  • 11. Intensive care stay duration [ Time Frame: Day 30 ]
  • 12. Hospital stay duration [ Time Frame: Day 30 ]
  • 13. Renal replacement therapy need [ Time Frame: Day 30, month 6, month 12 post- transplant ]
  • 14. Intraoperative thromboelastogram result [ Time Frame: In transplant surgery ]
  • 15. Histological evidence of reperfusion injury [ Time Frame: 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).
  • 16. Evidence of biliary stenosis in magnetic resonance cholangiography (MRS). [ Time Frame: 6 months after transplantation. ]

Eligibility Criteria

  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Maria Cortell 0034961246711 investigacion_clinica@iislafe.es

Locations

Spain
Hospital Universitario y Politécnico La Fe
Valencia

Sponsors and Collaborators

Instituto de Investigacion Sanitaria La Fe

More Information