Effectiveness of N-acetylcysteine on Preservation Solution During Liver Transplantation

Unspecified Complication of Liver Transplant Clinical Trial

Official title:

Effectiveness of N-acetylcysteine on Preservation Solution During Liver Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01866644
• Other study ID #: NAC400
• Status: Completed
• Phase: Phase 3
• Start date: September 2011
• Est. completion date: June 2016

Study information

• Verified date: June 2018
• Source: Instituto de Investigacion Sanitaria La Fe
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 214
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 95 Years

Eligibility

Inclusion Criteria:

• All grafts perfused by extraction for liver transplantation.

Exclusion Criteria:

• < 18 years

• Allergy to NAC

• Grafts considered invalid for liver transplantation after perfusion

• Hepatitis fulminant

• Retransplantation

• Split

• > 10 hours of cold ischemia

• Patients with asthma

Related Conditions & MeSH terms

• Unspecified Complication of Liver Transplant

Intervention

Drug:
• N-acetylcysteine
Bath transplanted liver with N-acetylcysteine
• Saline
Bath saline transplanted liver

Locations

Country	Name	City	State
Spain	Hospital Universitari i Politècnic La Fe	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Instituto de Investigacion Sanitaria La Fe

Country where clinical trial is conducted

Spain, 

References & Publications (16)

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. — View Citation

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. — View Citation

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. — View Citation

Himmelfarb J, Hakim RM. Oxidative stress in uremia. Curr Opin Nephrol Hypertens. 2003 Nov;12(6):593-8. Review. — View Citation

Lopez-Andujar R, Deusa S, Montalvá 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. — View Citation

Marczin N, Bundy RE, Hoare GS, Yacoub M. Redox regulation following cardiac ischemia and reperfusion. Coron Artery Dis. 2003 Apr;14(2):123-33. Review. — View Citation

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. Epub 2003 Apr 8. — View Citation

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. Erratum in: Transplantation. 2004 Aug 15;78(3):489. — View Citation

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. — View Citation

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. — View Citation

Selzner N, Rudiger H, Graf R, Clavien PA. Protective strategies against ischemic injury of the liver. Gastroenterology. 2003 Sep;125(3):917-36. Review. — View Citation

Taniyama Y, Griendling KK. Reactive oxygen species in the vasculature: molecular and cellular mechanisms. Hypertension. 2003 Dec;42(6):1075-81. Epub 2003 Oct 27. Review. — View Citation

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. — View Citation

Thies JC, Teklote J, Clauer U, Töx 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. — View Citation

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. — View Citation

Zafarullah M, Li WQ, Sylvester J, Ahmad M. Molecular mechanisms of N-acetylcysteine actions. Cell Mol Life Sci. 2003 Jan;60(1):6-20. Review. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	To assess the existence of side effects from the use of n-acetylcysteine on liver preservation solution usual.		One week after treatment
Secondary	Reduction of postoperative renal disfunction		One week after treatment
Secondary	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
Secondary	Histological changes	Two biopsies which are going to be done in donor graft before and after reperfusion.	During harvesting