Use of N-Acetylcysteine During Liver Procurement

NCT01394497 | Completed Phase 2 DMC

• 1 other identifier: 1635P
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

Randomized prospective study on the impact on the post-LT outcome by the infusion of N-acetylcysteine (NAC) during the liver procurement procedure, as an anti-oxidant agent to reduce the ischemia-reperfusion damage of organs for liver transplantation (LT).

Conditions

Liver Failure; Liver Failure, Acute; Liver Diseases; Carcinoma, Hepatocellular; Liver Neoplasms

Keywords

Liver Transplantation; Graft Survival; Graft Rejection; Primary Graft Dysfunction; Tissue and Organ Harvesting; Tissue and Organ Procurement; Tissue Donors; Cold Ischemia

Outcome Measures

Primary Outcomes (1)

• Graft survival

  up to 60 months

Secondary Outcomes (2)

• Patient survival

  up to 60 months

• Primary graft dysfunction

  up to 60 months

Study Arms (2)

NAC procurement protocol

EXPERIMENTAL

The allocated organ, in addition to the standard procedure, was treated with a systemic NAC infusion before initiating the liver harvesting procedure, and a loco-regional infusion into the portal vein before cross-clamping.

Drug: N-acetylcystein

Standard procurement procedure

NO INTERVENTION

Allocated organ was treated according to the centre's standard procurement procedure: a modified double perfusion technique, where donor livers are gravity-perfused in situ via the aorta and portal vein with Celsior solution at 4 °C. After hepatectomy, donor livers were further perfused at the back-table with Celsior solution and then stored in conventional bags containing the same solution at 4 °C until transplantation.

Interventions

N-acetylcystein DRUG

15 min systemic NAC infusion of the donor (30 mg/kg, maximum dose 3000 mg) diluted into 500 ml 5 % glucose solution, 30 min before initiating the liver harvesting procedure, and a loco-regional infusion (150 mg/kg of estimated liver weight, maximum dose 300 mg) into the portal vein 5 min before cross-clamping.

Also known as: Fluimucil (Zambon, Italy), ACC (Hexal AG), Acemuc (Betapharm, Germany), Acetyst (Ristert, Germany), Acetadote (Cumberland Pharmaceuticals), Asist (Bilim Pharmaceuticals, Turkey), Brunac eyedrops (Bruschettini, Italy), Fluimukan (Lek, Slovenia), Flumil (Pharmazam, Spain), Lysox (Menarini), Mucinac (Cipla, India), Mucohelp (Neiss Labs, India), Mucolysin (Sandoz), Mucomelt (Venus Remedies, India), MUCOMIX (Samarth Life Sciences, India), Mucomyst (Bristol-Myers Squibb), Nytex (Pharos,Indonesia), Parvolex (GSK), PharmaNAC (BioAdvantex Pharma Inc., North America), Rheunac (Tree Of Life, Israel), Solmucaïne (IBSA, Switzerland), Trebon N (Uni-pharma)

NAC procurement protocol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• all consecutive subjects with chronic liver disease undergoing first Liver Transplantation receiving deceased donor livers

You may not qualify if:

• recipients with acute liver disease;
• paediatric patients or adult patients receiving a liver from a paediatric donor;
• patients undergoing multiple-organ transplantation;
• patients undergoing re-transplantation of the Liver;
• patients undergoing living donor Liver Transplantation

Sponsors & Collaborators

• Azienda Ospedaliera di Padova: lead

Study Sites (1)

Azienda Ospedaliera di Padova

Padua, Padova, 35128, Italy

Location

Related Publications (2)

• D'Amico F, Vitale A, Gringeri E, Valmasoni M, Carraro A, Brolese A, Zanus G, Neri D, Boccagni P, Violi P, Pauletto A, D'Amico FE, D'Amico DF, Cillo U. SYSTEMIC AND LOCO-REGIONAL INFUSION OF N-ACETILCISTEINA DURING LIVER PROCUREMENT: A PROSPECTIVE RANDOMIZED CONTROLLED STUDY (Abstract# 488), The International Liver Transplantation Society: 14th Annual International Congress, July 9-12, 2008, Paris, France. Liver Transplantation, 14: S1-S269. doi: 10.1002/lt.21569

  RESULT

• D'Amico F, Vitale A, Piovan D, Bertacco A, Ramirez Morales R, Chiara Frigo A, Bassi D, Bonsignore P, Gringeri E, Valmasoni M, Garbo G, Lodo E, D'Amico FE, Scopelliti M, Carraro A, Gambato M, Brolese A, Zanus G, Neri D, Cillo U. Use of N-acetylcysteine during liver procurement: a prospective randomized controlled study. Liver Transpl. 2013 Feb;19(2):135-44. doi: 10.1002/lt.23527. Epub 2012 Sep 26.

  PMID: 22859317 RESULT

Related Links

• Hepatobiliary surgery and Liver Transplantation Unit, University Hospital of Padua (Italy)

MeSH Terms

Conditions

Liver Failure; Liver Failure, Acute; Liver Diseases; Carcinoma, Hepatocellular; Liver Neoplasms; Primary Graft Dysfunction

Interventions

Acetylcysteine; N-monoacetylcystine; halofantrine

Condition Hierarchy (Ancestors)

Hepatic Insufficiency; Digestive System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Reperfusion Injury; Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Umberto Cillo, MD

  Azienda Ospedaliera di Padova

  STUDY DIRECTOR

• Francesco D'Amico, MD

  Azienda Ospedaliera di Padova

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Hepatobiliary Surgery and Liver Transplantation Unit

Study Record Dates

• First Submitted: July 12, 2011
• First Posted: July 14, 2011
• Study Start: December 1, 2006
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: February 18, 2013

Record last verified: 2013-02

Locations

IT (1)