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Evaluate the effectiveness of the administration produced antioxidant N-acetylcysteine (NAC), decreasing the incidence of primary graft dysfunction and primary failure. The degree of dysfunction will be monitored by the method of LIMON, metabonomics techniques and according to the latest published validation Liver Transplantation (16 943-949 2010), total billirrubina greater than 10 mg / dl, INR greater than 1.6 in the seventh postoperative day and alanine or aspartate aminotransferase greater than 2000 IU / L in the first seven days. Liver dysfunction is considered, the presence of a transaminase value> 2000 IU / L 1-7 postoperative day or BT> 10 mg / dl or INR> 1.6, both only in the 7th postoperative day (Olthoff et al Liver Transplantation 16,943 -949 2010).
The reason of this study is to evaluate the efficacy of the use of n-acetylcysteine in liver transplant, by administering it in the perfusion liquid, at the time of extraction of the liver of the donor to improve the damage caused by ischemia / reperfusion. The dose is 400 mg in the portal perfusion liquid.
The study included all considered valid and perfused livers. Patients are randomized to contain no drug or n-acetylcysteine by randomization. Then analyzed using blood tests and in the receiver and daily during the first seven days post-transplant hepatic dysfunction parameters, in order to objectify if liver function improves after administration of the antioxidant (n-acetylcysteine ). Safety assessments were performed with intraoperative monitoring anesthetic depth, postoperative parameters of liver and kidney function and graft pathologic examination after perfusion.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| N-acetylcysteine | Experimental | At portal level, a cannula is inserted with the usual technique of infusion of 3000 ml of preservation fluid to free fall as containing or not scrambling inserted by the NAC scrub nurse then (400 mg of N-acetylcysteine at 10%, 4 ml ). |
|
| Saline | Placebo Comparator | With usual technique |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| N-acetylcysteine | Drug | Bath transplanted liver with N-acetylcysteine |
|
| Measure | Description | Time Frame |
|---|---|---|
| The incidence of primary graft dysfunction and primary failure | Evaluate the incidence of primary graft dysfunction and primary failure in each group of treatment. | One week after treatment |
| Measure | Description | Time Frame |
|---|---|---|
| To assess the existence of side effects from the use of n-acetylcysteine on liver preservation solution usual. | One week after treatment | |
| Reduction of postoperative renal disfunction | One week after treatment |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rafael Lopez Andujar, PhD | Hospital Universitario La Fe | Principal Investigator |
| Concepcion Gómez i Gavara, MD | Hospital Universitario La Fe | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Universitari i Politècnic La Fe | Valencia | 46026 | Spain |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12613655 | Background | Zafarullah M, Li WQ, Sylvester J, Ahmad M. Molecular mechanisms of N-acetylcysteine actions. Cell Mol Life Sci. 2003 Jan;60(1):6-20. doi: 10.1007/s000180300001. | |
| 11029607 | Background | De Rosa SC, Zaretsky MD, Dubs JG, Roederer M, Anderson M, Green A, Mitra D, Watanabe N, Nakamura H, Tjioe I, Deresinski SC, Moore WA, Ela SW, Parks D, Herzenberg LA, Herzenberg LA. N-acetylcysteine replenishes glutathione in HIV infection. Eur J Clin Invest. 2000 Oct;30(10):915-29. doi: 10.1046/j.1365-2362.2000.00736.x. |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Jun 6, 2019 | |
| Reset | Jul 30, 2019 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Jun 6, 2019 | Jul 30, 2019 |
| ID | Term |
|---|---|
| D000111 | Acetylcysteine |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D003545 | Cysteine |
| D000603 | Amino Acids, Sulfur |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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| Saline | Drug | Bath saline transplanted liver |
|
|
| Assess levels of glutathione stores achieved following administration of NAC | During the harvesting and implantation in the recipient liver three liver biopsies will be performed which will be assessed by determining metabonomics metabolites of the transsulfuration pathway and GSH levels. | During harvesting |
| Histological changes | Two biopsies which are going to be done in donor graft before and after reperfusion. | During harvesting |
| 2897100 | Background | Abstracts of the Brain Research Association meeting, Mechanisms of Recovery of Function after Brain Damage. Oxford, U.K., 11 January 1988. Neurosci Lett Suppl. 1988;32:S107-17. No abstract available. |
| 14564195 | Background | Himmelfarb J, Hakim RM. Oxidative stress in uremia. Curr Opin Nephrol Hypertens. 2003 Nov;12(6):593-8. doi: 10.1097/00041552-200311000-00004. |
| 12682719 | Background | Molnar Z, Szakmany T, Koszegi T. Prophylactic N-acetylcysteine decreases serum CRP but not PCT levels and microalbuminuria following major abdominal surgery. A prospective, randomised, double-blinded, placebo-controlled clinical trial. Intensive Care Med. 2003 May;29(5):749-55. doi: 10.1007/s00134-003-1723-1. Epub 2003 Apr 8. |
| 14581295 | Background | Taniyama Y, Griendling KK. Reactive oxygen species in the vasculature: molecular and cellular mechanisms. Hypertension. 2003 Dec;42(6):1075-81. doi: 10.1161/01.HYP.0000100443.09293.4F. Epub 2003 Oct 27. |
| 14712439 | Background | Raj DS, Lim G, Levi M, Qualls C, Jain SK. Advanced glycation end products and oxidative stress are increased in chronic allograft nephropathy. Am J Kidney Dis. 2004 Jan;43(1):154-60. doi: 10.1053/j.ajkd.2003.09.021. |
| 11153617 | Background | Rank N, Michel C, Haertel C, Lenhart A, Welte M, Meier-Hellmann A, Spies C. N-acetylcysteine increases liver blood flow and improves liver function in septic shock patients: results of a prospective, randomized, double-blind study. Crit Care Med. 2000 Dec;28(12):3799-807. doi: 10.1097/00003246-200012000-00006. |
| 11422213 | Background | Taut FJ, Schmidt H, Zapletal CM, Thies JC, Grube C, Motsch J, Klar E, Martin E. N-acetylcysteine induces shedding of selectins from liver and intestine during orthotopic liver transplantation. Clin Exp Immunol. 2001 May;124(2):337-41. doi: 10.1046/j.1365-2249.2001.01531.x. |
| 9665023 | Background | Thies JC, Teklote J, Clauer U, Tox U, Klar E, Hofmann WJ, Herfarth C, Otto G. The efficacy of N-acetylcysteine as a hepatoprotective agent in liver transplantation. Transpl Int. 1998;11 Suppl 1:S390-2. doi: 10.1007/s001470050505. |
| 12655276 | Background | Marczin N, Bundy RE, Hoare GS, Yacoub M. Redox regulation following cardiac ischemia and reperfusion. Coron Artery Dis. 2003 Apr;14(2):123-33. doi: 10.1097/00019501-200304000-00005. No abstract available. |
| 12949736 | Background | Selzner N, Rudiger H, Graf R, Clavien PA. Protective strategies against ischemic injury of the liver. Gastroenterology. 2003 Sep;125(3):917-36. doi: 10.1016/s0016-5085(03)01048-5. |
| 17902131 | Background | D'Amico F, Vitale A, Gringeri E, Valmasoni M, Carraro A, Brolese A, Zanus G, Boccagni P, D'Amico DF, Cillo U. Liver transplantation using suboptimal grafts: impact of donor harvesting technique. Liver Transpl. 2007 Oct;13(10):1444-50. doi: 10.1002/lt.21268. |
| 19938119 | Background | Lopez-Andujar R, Deusa S, Montalva E, San Juan F, Moya A, Pareja E, DeJuan M, Berenguer M, Prieto M, Mir J. Comparative prospective study of two liver graft preservation solutions: University of Wisconsin and Celsior. Liver Transpl. 2009 Dec;15(12):1709-17. doi: 10.1002/lt.21945. |
| 15239618 | Background | Pedotti P, Cardillo M, Rigotti P, Gerunda G, Merenda R, Cillo U, Zanus G, Baccarani U, Berardinelli ML, Boschiero L, Caccamo L, Calconi G, Chiaramonte S, Dal Canton A, De Carlis L, Di Carlo V, Donati D, Montanaro D, Pulvirenti A, Remuzzi G, Sandrini S, Valente U, Scalamogna M. A comparative prospective study of two available solutions for kidney and liver preservation. Transplantation. 2004 May 27;77(10):1540-5. doi: 10.1097/01.tp.0000132278.00441.cf. |
| 15280686 | Background | Varadarajan R, Golden-Mason L, Young L, McLoughlin P, Nolan N, McEntee G, Traynor O, Geoghegan J, Hegarty JE, O'Farrelly C. Nitric oxide in early ischaemia reperfusion injury during human orthotopic liver transplantation. Transplantation. 2004 Jul 27;78(2):250-6. doi: 10.1097/01.tp.0000128188.45553.8c. |
| 33044432 | Derived | Gomez-Gavara C, Moya-Herraiz A, Hervas D, Perez-Rojas J, LaHoz A, Lopez-Andujar R. The Potential Role of Efficacy and Safety Evaluation of N-Acetylcysteine Administration During Liver Procurement. The NAC-400 Single Center Randomized Controlled Trial. Transplantation. 2021 Oct 1;105(10):2245-2254. doi: 10.1097/TP.0000000000003487. |
| D000596 |
| Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |