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

Liver Transplant Clinical Trial

— ORGANOXLAFE  

Official title:

Clinical Trial to Compare the Efficacy of Ex-situ Normothermic Perfusion With Cold Storage in the Transplant With Steatotic Liver Graft.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03930459
• Other study ID #: ORGANOXLAFE
• Status: Terminated
• Phase: N/A
• Start date: April 26, 2019
• Est. completion date: April 4, 2023

Study information

• Verified date: August 2019
• Source: Instituto de Investigacion Sanitaria La Fe
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: April 4, 2023
• Est. primary completion date: April 4, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Liver Transplant

Intervention

Procedure:
• Static cold storage (SCS)
The liver is flushed and cooled with specialist preservation fluid, then stored in an icebox.

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.

Locations

Country	Name	City	State
Spain	Hospital Universitario y Politécnico La Fe	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Instituto de Investigacion Sanitaria La Fe

Country where clinical trial is conducted

Spain, 

References & Publications (13)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak of transaminases (AST and ALT)		Day 1 post-transplant.
Primary	Peak of transaminases (AST and ALT)		Day 3 post-transplant.
Primary	Peak of transaminases (AST and ALT)		Day 5 post-transplant.
Primary	Peak of transaminases (AST and ALT) l		Day 7 post-transplant.
Secondary	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.
Secondary	Graft survival		Day 30 post-transplant, month 6 post-transplant, month 12 post-transplant.
Secondary	Patient survival		Day 30 post-transplant, month 6 post-transplant, month 12 post-transplant.
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Early graft dysfunction	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	7 days post-transplant
Secondary	Intensive care stay duration		Day 30
Secondary	Hospital stay duration		Day 30
Secondary	Renal replacement therapy need		Day 30, month 6, month 12 post- transplant
Secondary	Intraoperative thromboelastogram result		In transplant surgery
Secondary	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
Secondary	Evidence of biliary stenosis in magnetic resonance cholangiography (MRS).		6 months after transplantation.