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

Instituto de Investigacion Sanitaria La Fe

Status: Terminated

Conditions: Liver Transplant

Treatments: Device: Normothermic machine perfusion (NMP); Procedure: Static cold storage (SCS)

Study type: Interventional

Funder types: Other

Identifiers

NCT03930459

ORGANOXLAFE

Details and patient eligibility

About

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.

Full 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.

Enrollment: 7 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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7 participants in 2 patient groups

Static cold storage (SCS)

Experimental group

Description:

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.

Treatment:

Procedure: Static cold storage (SCS)

Normothermic machine perfusion (NMP)

Experimental group

Description:

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.

Treatment:

Device: Normothermic machine perfusion (NMP)