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Effectiveness of N-acetylcysteine on Preservation Solution During Liver Transplantation

Phase 3
Completed
Conditions
Unspecified Complication of Liver Transplant
Interventions
Registration Number
NCT01866644
Lead Sponsor
Instituto de Investigacion Sanitaria La Fe
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).

Detailed 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 & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
214
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
SalineSalineWith usual technique
N-acetylcysteineN-acetylcysteineAt 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 ).
Primary Outcome Measures
NameTimeMethod
The incidence of primary graft dysfunction and primary failureOne week after treatment

Evaluate the incidence of primary graft dysfunction and primary failure in each group of treatment.

Secondary Outcome Measures
NameTimeMethod
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 disfunctionOne week after treatment
Assess levels of glutathione stores achieved following administration of NACDuring harvesting

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.

Histological changesDuring harvesting

Two biopsies which are going to be done in donor graft before and after reperfusion.

Trial Locations

Locations (1)

Hospital Universitari i Politècnic La Fe

🇪🇸

Valencia, Spain

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