NCT01866644

Brief 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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
214

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Sep 2011

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2011

Completed
8 months until next milestone

First Submitted

Initial submission to the registry

April 18, 2012

Completed
1.1 years until next milestone

First Posted

Study publicly available on registry

May 31, 2013

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2016

Completed
Last Updated

August 13, 2018

Status Verified

June 1, 2018

Enrollment Period

4.8 years

First QC Date

April 18, 2012

Last Update Submit

August 9, 2018

Conditions

Unspecified Complication of Liver Transplant

Keywords

Liver transplantation, n-acetylcysteine

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (4)

  • 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

  • Assess levels of glutathione stores achieved following administration of NAC

    During harvesting

  • Histological changes

    During harvesting

Study Arms (2)

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 ).

Drug: N-acetylcysteine

Saline

PLACEBO COMPARATOR

With usual technique

Drug: Saline

Interventions

N-acetylcysteineDRUG

Bath transplanted liver with N-acetylcysteine

Also known as: Flumil Solution injectable 300 Mg
N-acetylcysteine
SalineDRUG

Bath saline transplanted liver

Also known as: It's not describe in a protocol
Saline

Eligibility Criteria

Age18 Years - 95 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • All grafts perfused by extraction for liver transplantation.

You may not qualify if:

  • \< 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hospital Universitari i Politècnic La Fe

Valencia, 46026, Spain

Location

Related Publications (17)

  • 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.

    PMID: 12613655BACKGROUND

  • 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.

    PMID: 11029607BACKGROUND

  • 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.

    PMID: 2897100BACKGROUND

  • Himmelfarb J, Hakim RM. Oxidative stress in uremia. Curr Opin Nephrol Hypertens. 2003 Nov;12(6):593-8. doi: 10.1097/00041552-200311000-00004.

    PMID: 14564195BACKGROUND

  • 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.

    PMID: 12682719BACKGROUND

  • 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.

    PMID: 14581295BACKGROUND

  • 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.

    PMID: 14712439BACKGROUND

  • 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.

    PMID: 11153617BACKGROUND

  • 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.

    PMID: 11422213BACKGROUND

  • 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.

    PMID: 9665023BACKGROUND

  • 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.

    PMID: 12655276BACKGROUND

  • 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.

    PMID: 12949736BACKGROUND

  • 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.

    PMID: 17902131BACKGROUND

  • 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.

    PMID: 19938119BACKGROUND

  • 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.

    PMID: 15239618BACKGROUND

  • 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.

    PMID: 15280686BACKGROUND

  • 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.

    PMID: 33044432DERIVED

MeSH Terms

Interventions

AcetylcysteineSodium Chloride

Intervention Hierarchy (Ancestors)

CysteineAmino Acids, SulfurSulfur CompoundsOrganic ChemicalsAmino AcidsAmino Acids, Peptides, and ProteinsChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium Compounds

Study Officials

  • Rafael Lopez Andujar, PhD

    Hospital Universitario La Fe

    PRINCIPAL INVESTIGATOR

  • Concepcion Gómez i Gavara, MD

    Hospital Universitario La Fe

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 18, 2012

First Posted

May 31, 2013

Study Start

September 1, 2011

Primary Completion

June 1, 2016

Study Completion

June 1, 2016

Last Updated

August 13, 2018

Record last verified: 2018-06

Locations

ES(1)