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

NCT03930459 | Terminated

• 1 other identifier: ORGANOXLAFE
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Liver Transplant

Outcome Measures

Primary Outcomes (4)

• Peak of transaminases (AST and ALT)

  Day 1 post-transplant.

• Peak of transaminases (AST and ALT)

  Day 3 post-transplant.

• Peak of transaminases (AST and ALT)

  Day 5 post-transplant.

• Peak of transaminases (AST and ALT) l

  Day 7 post-transplant.

Secondary Outcomes (16)

• Primary graft failure

  Day 10 post-transplant.

• Graft survival

  Day 30 post-transplant, month 6 post-transplant, month 12 post-transplant.

• 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

• 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

Study Arms (2)

Static cold storage (SCS)

EXPERIMENTAL

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)

Normothermic machine perfusion (NMP)

EXPERIMENTAL

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)

Interventions

Static cold storage (SCS) PROCEDURE

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

Static cold storage (SCS)

Normothermic machine perfusion (NMP) DEVICE

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

Normothermic machine perfusion (NMP)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Instituto de Investigacion Sanitaria La Fe: lead

Study Sites (1)

Hospital Universitario y Politécnico La Fe

Valencia, Spain

Location

Related Publications (13)

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  PMID: 9870271 BACKGROUND

• 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.

  PMID: 11972552 BACKGROUND

• 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.

  PMID: 11907414 BACKGROUND

• 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.

  PMID: 8985288 BACKGROUND

• 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.

  PMID: 8184469 BACKGROUND

• 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.

  PMID: 8892594 BACKGROUND

• 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.

  PMID: 15273542 BACKGROUND

• 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.

  PMID: 20677285 BACKGROUND

• 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.

  PMID: 22168355 BACKGROUND

• 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.

  PMID: 18383079 BACKGROUND

• 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.

  PMID: 12859537 BACKGROUND

• 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.

  PMID: 19545716 BACKGROUND

• 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.

  PMID: 29670285 BACKGROUND

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2019
• First Posted: April 29, 2019
• Study Start: April 26, 2019
• Primary Completion: April 4, 2023
• Study Completion: April 4, 2023
• Last Updated: September 29, 2023

Record last verified: 2019-08

Locations

ES (1)