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

NCT ID: NCT03930459

Last Updated: 2023-09-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

7 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-04-26

Study Completion Date

2023-04-04

Brief Summary

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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

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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.

Conditions

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Liver Transplant

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Static cold storage (SCS)

Intervention Type PROCEDURE

The liver is flushed and cooled with specialist preservation fluid, then stored in an icebox.

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.

Group Type EXPERIMENTAL

Normothermic machine perfusion (NMP)

Intervention Type DEVICE

During NMP, the liver is perfused with oxygenated blood, medications and nutrients at normal body temperature to maintain a physiological milieu.

Interventions

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Static cold storage (SCS)

The liver is flushed and cooled with specialist preservation fluid, then stored in an icebox.

Intervention Type PROCEDURE

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.

Intervention Type DEVICE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Instituto de Investigacion Sanitaria La Fe

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hospital Universitario y Politécnico La Fe

Valencia, , Spain

Site Status

Countries

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Spain

References

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Garcia-Valdecasas JC, Tabet J, Valero R, Taura P, Rull R, Garcia F, Montserrat E, Gonzalez FX, Ordi J, Beltran J, Lopez-Boado MA, Deulofeu R, Angas J, Cifuentes A, Visa J. Liver conditioning after cardiac arrest: the use of normothermic recirculation in an experimental animal model. Transpl Int. 1998;11(6):424-32. doi: 10.1007/s001470050169.

Reference Type BACKGROUND
PMID: 9870271 (View on PubMed)

St Peter SD, Imber CJ, Lopez I, Hughes D, Friend PJ. Extended preservation of non-heart-beating donor livers with normothermic machine perfusion. Br J Surg. 2002 May;89(5):609-16. doi: 10.1046/j.1365-2168.2002.02052.x.

Reference Type BACKGROUND
PMID: 11972552 (View on PubMed)

Imber CJ, St Peter SD, Lopez de Cenarruzabeitia I, Pigott D, James T, Taylor R, McGuire J, Hughes D, Butler A, Rees M, Friend PJ. Advantages of normothermic perfusion over cold storage in liver preservation. Transplantation. 2002 Mar 15;73(5):701-9. doi: 10.1097/00007890-200203150-00008.

Reference Type BACKGROUND
PMID: 11907414 (View on PubMed)

Gaffey MJ, Boyd JC, Traweek ST, Ali MA, Rezeig M, Caldwell SH, Iezzoni JC, McCullough C, Stevenson WC, Khuroo S, Nezamuddin N, Ishitani MB, Pruett TL. Predictive value of intraoperative biopsies and liver function tests for preservation injury in orthotopic liver transplantation. Hepatology. 1997 Jan;25(1):184-9. doi: 10.1002/hep.510250134.

Reference Type BACKGROUND
PMID: 8985288 (View on PubMed)

Karayalcin K, Mirza DF, Harrison RF, Da Silva RF, Hubscher SG, Mayer AD, Buckels JA, McMaster P. The role of dynamic and morphological studies in the assessment of potential liver donors. Transplantation. 1994 May 15;57(9):1323-7. doi: 10.1097/00007890-199405150-00006.

Reference Type BACKGROUND
PMID: 8184469 (View on PubMed)

Abraham S, Furth EE. Quantitative evaluation of histological features in "time-zero" liver allograft biopsies as predictors of rejection or graft failure: receiver-operating characteristic analysis application. Hum Pathol. 1996 Oct;27(10):1077-84. doi: 10.1016/s0046-8177(96)90287-7.

Reference Type BACKGROUND
PMID: 8892594 (View on PubMed)

Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. doi: 10.1097/01.sla.0000133083.54934.ae.

Reference Type BACKGROUND
PMID: 15273542 (View on PubMed)

Olthoff KM, Kulik L, Samstein B, Kaminski M, Abecassis M, Emond J, Shaked A, Christie JD. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl. 2010 Aug;16(8):943-9. doi: 10.1002/lt.22091.

Reference Type BACKGROUND
PMID: 20677285 (View on PubMed)

Chung IS, Kim HY, Shin YH, Ko JS, Gwak MS, Sim WS, Kim GS, Lee SK. Incidence and predictors of post-reperfusion syndrome in living donor liver transplantation. Clin Transplant. 2012 Jul-Aug;26(4):539-43. doi: 10.1111/j.1399-0012.2011.01568.x. Epub 2011 Dec 14.

Reference Type BACKGROUND
PMID: 22168355 (View on PubMed)

Hilmi I, Horton CN, Planinsic RM, Sakai T, Nicolau-Raducu R, Damian D, Gligor S, Marcos A. The impact of postreperfusion syndrome on short-term patient and liver allograft outcome in patients undergoing orthotopic liver transplantation. Liver Transpl. 2008 Apr;14(4):504-8. doi: 10.1002/lt.21381.

Reference Type BACKGROUND
PMID: 18383079 (View on PubMed)

Glanemann M, Langrehr JM, Stange BJ, Neumann U, Settmacher U, Steinmuller T, Neuhaus P. Clinical implications of hepatic preservation injury after adult liver transplantation. Am J Transplant. 2003 Aug;3(8):1003-9. doi: 10.1034/j.1600-6143.2003.00167.x.

Reference Type BACKGROUND
PMID: 12859537 (View on PubMed)

Eisenbach C, Encke J, Merle U, Gotthardt D, Weiss KH, Schneider L, Latanowicz S, Spiegel M, Engelmann G, Stremmel W, Buchler MW, Schmidt J, Weigand MA, Sauer P. An early increase in gamma glutamyltranspeptidase and low aspartate aminotransferase peak values are associated with superior outcomes after orthotopic liver transplantation. Transplant Proc. 2009 Jun;41(5):1727-30. doi: 10.1016/j.transproceed.2009.01.084.

Reference Type BACKGROUND
PMID: 19545716 (View on PubMed)

Nasralla D, Coussios CC, Mergental H, Akhtar MZ, Butler AJ, Ceresa CDL, Chiocchia V, Dutton SJ, Garcia-Valdecasas JC, Heaton N, Imber C, Jassem W, Jochmans I, Karani J, Knight SR, Kocabayoglu P, Malago M, Mirza D, Morris PJ, Pallan A, Paul A, Pavel M, Perera MTPR, Pirenne J, Ravikumar R, Russell L, Upponi S, Watson CJE, Weissenbacher A, Ploeg RJ, Friend PJ; Consortium for Organ Preservation in Europe. A randomized trial of normothermic preservation in liver transplantation. Nature. 2018 May;557(7703):50-56. doi: 10.1038/s41586-018-0047-9. Epub 2018 Apr 18.

Reference Type BACKGROUND
PMID: 29670285 (View on PubMed)

Other Identifiers

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ORGANOXLAFE

Identifier Type: -

Identifier Source: org_study_id

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