Sugammadex Versus Neostigmine in Patients With Liver Cirrhosis Undergoing Liver Resection

NCT02414880 | Completed Phase 4 DMC

• 1 other identifier: Suga-Neo
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Liver cirrhosis is a progressive disease characterized by loss of functional hepatocytes that substantially affects drug pharmacokinetics. Rocuronium onset time is longer and recovery time from it is prolonged in cirrhotic patients than in those with normal liver function. This randomized controlled study is designed to compare the pharmacodynamic profiles of sugammadex and neostigmine when used for the antagonism of moderate degree of rocuronium-induced neuromuscular block in cirrhotic patients undergoing liver resection and in patients with preoperative normal liver functions undergoing liver resection.

Conditions

Cirrhosis and Chronic Liver Disease

Keywords

Sugammadex; Neostigmine; Rocuronium; Cirrhosis; Liver resection; Neuromuscular

Outcome Measures

Primary Outcomes (1)

• The time from reversal to Train-of-four (TOF) ratio of 0.9

  The time from the administration of Sugammadex or Neostigmine till recovery of the TOF ratio to 0.9

  15 min

Secondary Outcomes (7)

• The time from reversal to Train-of-four (TOF) ratio of 1

  30 min

• Length of stay in the post-anesthesia care unit (PACU)

  4 hours

• Time from last Rocuronium dose to Train-of-four (TOF) ratio of 0.9

  1 hour

• Duration of action of the initial intubating dose of Rocuronium

  45 min

• Incidence of postoperative re-curarization

  4 hours

Study Arms (4)

Sugammadex/ Normal liver

ACTIVE COMPARATOR

Patients with American Society of Anesthesiologists physical status (ASA) class I with normal preoperative liver functions undergoing liver resection. Rocuronium-induced neuromuscular blockade will be reversed at the end of the operation when two responses to train-of-four ulnar nerve stimulation are detected (T2) by injection of sugammadex 2mg/kg.

Drug: Sugammadex; Drug: Rocuronium

Neostigmine / Normal liver

ACTIVE COMPARATOR

Patients with American Society of Anesthesiologists physical status (ASA) class I with normal preoperative liver functions undergoing liver resection. Rocuronium-induced neuromuscular blockade will be reversed at the end of the operation when two responses to train-of-four ulnar nerve stimulation are detected (T2) by injection of neostigmine 50 micro-gram/kg combined with atropine 20 micro-gram/kg.

Drug: Neostigmine; Drug: Rocuronium

Sugammadex / Liver cirrhosis

ACTIVE COMPARATOR

Patients with liver cirrhosis, Child classification "A" with a Model for End-Stage Liver Disease (MELD) score \<10 undergoing liver resection. Rocuronium-induced neuromuscular blockade will be reversed at the end of the operation when two responses to train-of-four ulnar nerve stimulation are detected (T2) by injection of sugammadex 2mg/kg.

Drug: Sugammadex; Drug: Rocuronium

Neostigmine / Liver cirrhosis

ACTIVE COMPARATOR

Patients with liver cirrhosis, Child classification "A" with a Model for End-Stage Liver Disease (MELD) score \<10 undergoing liver resection. Rocuronium-induced neuromuscular blockade will be reversed at the end of the operation when two responses to train-of-four ulnar nerve stimulation are detected (T2) by injection of neostigmine 50 micro-gram/kg combined with atropine 20 micro-gram/kg.

Drug: Neostigmine; Drug: Rocuronium

Interventions

Sugammadex DRUG

Rocuronium-induced neuromuscular blockade will be reversed at the end of the operation when two responses to train-of-four ulnar nerve stimulation are detected (T2) by injection of sugammadex 2mg/kg.

Also known as: Bridion

Sugammadex / Liver cirrhosis; Sugammadex/ Normal liver

Neostigmine DRUG

Rocuronium-induced neuromuscular blockade will be reversed at the end of the operation when two responses to train-of-four ulnar nerve stimulation are detected (T2) by injection of neostigmine 50 micro-gram/kg combined with atropine 20 micro-gram/kg.

Also known as: Prostigmine

Neostigmine / Liver cirrhosis; Neostigmine / Normal liver

Rocuronium DRUG

An intubating dose of Rocuronium (0.6 mg/kg) will be given with induction of anesthesia and the degree of muscle relaxation will be evaluated through out the operation by recording the response of the hand muscles to train-of-four ulnar nerve stimulator (Mechanosensor Neuromuscular Transmission Module of General Electric AISYS Anaesthesia machine USA) according to the Good Clinical Research Practice (GCRP) guidelines for pharmacodynamic neuromuscular studies. Muscle relaxation will be maintained by additional top-up doses of Rocuronium (0.15mg/kg) which will be administered after detection of the first response to TOF stimulation (T1).

Also known as: Esmeron

Neostigmine / Liver cirrhosis; Neostigmine / Normal liver; Sugammadex / Liver cirrhosis; Sugammadex/ Normal liver

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• American Society of Anesthesiologists physical status (ASA) class I for patients with preoperative normal liver function test (two groups) and I-III for patients with liver cirrhosis (two groups).
• For the two "Liver Cirrhosis" groups: Patients with liver Cirrhosis with Child classification "A" and a Model for End-Stage Liver Disease (MELD) score \<10 undergoing Liver resection surgeries.
• For the two "Normal Liver" groups: Patients with normal preoperative liver functions undergoing Liver resection surgeries.

You may not qualify if:

• Co-existing neuromuscular disease.
• Body mass index more than 35 kg/m-2.
• Renal impairment.
• Medications known to affect neuromuscular transmission (e.g. Aminoglycoside antibiotics or Magnesium Sulphate).
• Bleeding tendency.
• Intra-operative adverse events (e.g. massive bleeding or hypothermia).

Sponsors & Collaborators

• Cairo University: lead
• National Liver Institute, Egypt: collaborator

Study Sites (1)

National Liver institute

Ḩadā’iq al Qubbah, Cairo Governorate, 11562, Egypt

Location

Related Publications (9)

• Schaller SJ, Fink H. Sugammadex as a reversal agent for neuromuscular block: an evidence-based review. Core Evid. 2013;8:57-67. doi: 10.2147/CE.S35675. Epub 2013 Sep 25.

  PMID: 24098155 BACKGROUND

• Edginton AN, Willmann S. Physiology-based simulations of a pathological condition: prediction of pharmacokinetics in patients with liver cirrhosis. Clin Pharmacokinet. 2008;47(11):743-52. doi: 10.2165/00003088-200847110-00005.

  PMID: 18840029 BACKGROUND

• Kopman AF, Eikermann M. Antagonism of non-depolarising neuromuscular block: current practice. Anaesthesia. 2009 Mar;64 Suppl 1:22-30. doi: 10.1111/j.1365-2044.2008.05867.x.

  PMID: 19222428 BACKGROUND

• Caldwell JE. Clinical limitations of acetylcholinesterase antagonists. J Crit Care. 2009 Mar;24(1):21-8. doi: 10.1016/j.jcrc.2008.08.003. Epub 2009 Jan 17.

  PMID: 19272535 BACKGROUND

• Naguib M. Sugammadex: another milestone in clinical neuromuscular pharmacology. Anesth Analg. 2007 Mar;104(3):575-81. doi: 10.1213/01.ane.0000244594.63318.fc.

  PMID: 17312211 BACKGROUND

• Nonaka T, Fujimoto M, Nishi M, Yamamoto T. [The effect of rocuronium and sugammadex in hepatic tumor patients without preoperative hepatic impairment]. Masui. 2013 Mar;62(3):304-8. Japanese.

  PMID: 23544332 BACKGROUND

• Batistaki C, Matsota P, Kalimeris K, Brountzos E, Kostopanagiotou G. Sugammadex antagonising rocuronium in three patients with liver dysfunction undergoing transjugular intrahepatic portosystemic shunt. Anaesth Intensive Care. 2012 May;40(3):556-7. No abstract available.

  PMID: 22577926 BACKGROUND

• Blobner M, Eriksson LI, Scholz J, Motsch J, Della Rocca G, Prins ME. Reversal of rocuronium-induced neuromuscular blockade with sugammadex compared with neostigmine during sevoflurane anaesthesia: results of a randomised, controlled trial. Eur J Anaesthesiol. 2010 Oct;27(10):874-81. doi: 10.1097/EJA.0b013e32833d56b7.

  PMID: 20683334 BACKGROUND

• Illman HL, Laurila P, Antila H, Meretoja OA, Alahuhta S, Olkkola KT. The duration of residual neuromuscular block after administration of neostigmine or sugammadex at two visible twitches during train-of-four monitoring. Anesth Analg. 2011 Jan;112(1):63-8. doi: 10.1213/ANE.0b013e3181fdf889. Epub 2010 Oct 26.

  PMID: 20978247 BACKGROUND

MeSH Terms

Conditions

Fibrosis

Interventions

Sugammadex; Neostigmine; Rocuronium

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

gamma-Cyclodextrins; Cyclodextrins; Macrocyclic Compounds; Polycyclic Compounds; Dextrins; Starch; Glucans; Polysaccharides; Carbohydrates; Phenylammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Androstanols; Androstanes; Steroids; Fused-Ring Compounds

Study Officials

• Mohamed Abdulatif Mohamed, M.D.

  Cairo University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Mohamed Abdulatif Mohamed, MD

Study Record Dates

• First Submitted: April 5, 2015
• First Posted: April 13, 2015
• Study Start: December 1, 2014
• Primary Completion: August 1, 2015
• Study Completion: September 1, 2015
• Last Updated: February 2, 2016

Record last verified: 2016-01

Locations

EG (1)