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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.
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Static cold storage (SCS) | Procedure | The liver is flushed and cooled with specialist preservation fluid, then stored in an icebox. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Primary graft failure | 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. | Day 10 post-transplant. |
| Graft survival |
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Inclusion Criteria:
LIVER DONOR:
LIVER RECIPIENT:
Exclusion Criteria:
LIVER DONOR:
LIVER RECIPIENT:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Universitario y Politécnico La Fe | Valencia | Spain |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 9870271 | Background | 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. | |
| 11972552 |
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| 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. |
|
| 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 | 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. | 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 |
| 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 |
| Early graft dysfunction | Defined by:
| 7 days post-transplant |
| 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 | Post-reperfusion biopsies will be compared with baseline pre-reperfusion biopsies and classified according to standard histological criteria (blind comparison to third parties). | In transplant surgery |
| Evidence of biliary stenosis in magnetic resonance cholangiography (MRS). | 6 months after transplantation. |
| 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. |
| 11907414 | 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. |
| 8985288 | 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. |
| 8184469 | 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. |
| 8892594 | 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. |
| 15273542 | 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. |
| 20677285 | 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. |
| 22168355 | 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. |
| 18383079 | 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. |
| 12859537 | 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. |
| 19545716 | 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. |
| 29670285 | 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. |