Sugammadex and Neostigmine at Residual Neuromuscular Blockade - Full Text View

Purpose

This study is designed to compare recovery times after reversal of a residual neuromuscular block (TOF-ratio 0.2) with different doses of either neostigmine or sugammadex.

Condition	Intervention
Residual Neuromuscular Block (TOF-ratio of 0.2)	Drug: Sugammadex Drug: Neostigmine Drug: Saline

Study Type:	Observational
Study Design:	Time Perspective: Prospective
Official Title:	Dose Finding Study for Sugammadex and Neostigmine at Residual Neuromuscular Blockade (T4/T1 = 0.2)

Resource links provided by NLM:

Drug Information available for: Neostigmine methylsulfate Phenylephrine Phenylephrine hydrochloride Oxymetazoline Oxymetazoline hydrochloride

U.S. FDA Resources

Further study details as provided by Technische Universität München:

Primary Outcome Measures:

Time to TOF-ratio 0.9 following the investigational drug [ Time Frame: Regular anesthesia time, approximately 1.5 hours ]

Enrollment:	99
Study Start Date:	March 2009
Study Completion Date:	December 2009
Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
Sgx 0.25 Sugammadex group: Different doses of sugammadex for reversal of shallow neuromuscular blockade	Drug: Sugammadex Single intravenous injection of either: Sugammadex 0.25 mg/kg (Sgx 0.25) Sugammadex 0.5 mg/kg (Sgx 0.5) Sugammadex 0.75 mg/kg (Sgx 0.75) Sugammadex 1.0 mg/kg (Sgx 1.0) Sugammadex 1.25 mg/kg (Sgx 1.25)
Sgx 0.5 Sugammadex group: Different doses of sugammadex for reversal of shallow neuromuscular blockade	Drug: Sugammadex Single intravenous injection of either: Sugammadex 0.25 mg/kg (Sgx 0.25) Sugammadex 0.5 mg/kg (Sgx 0.5) Sugammadex 0.75 mg/kg (Sgx 0.75) Sugammadex 1.0 mg/kg (Sgx 1.0) Sugammadex 1.25 mg/kg (Sgx 1.25)
Sgx 0.75 Sugammadex group: Different doses of sugammadex for reversal of shallow neuromuscular blockade	Drug: Sugammadex Single intravenous injection of either: Sugammadex 0.25 mg/kg (Sgx 0.25) Sugammadex 0.5 mg/kg (Sgx 0.5) Sugammadex 0.75 mg/kg (Sgx 0.75) Sugammadex 1.0 mg/kg (Sgx 1.0) Sugammadex 1.25 mg/kg (Sgx 1.25)
Sgx 1.0 Sugammadex group: Different doses of sugammadex for reversal of shallow neuromuscular blockade	Drug: Sugammadex Single intravenous injection of either: Sugammadex 0.25 mg/kg (Sgx 0.25) Sugammadex 0.5 mg/kg (Sgx 0.5) Sugammadex 0.75 mg/kg (Sgx 0.75) Sugammadex 1.0 mg/kg (Sgx 1.0) Sugammadex 1.25 mg/kg (Sgx 1.25)
Sgx 1.25 Sugammadex group: Different doses of sugammadex for reversal of shallow neuromuscular blockade	Drug: Sugammadex Single intravenous injection of either: Sugammadex 0.25 mg/kg (Sgx 0.25) Sugammadex 0.5 mg/kg (Sgx 0.5) Sugammadex 0.75 mg/kg (Sgx 0.75) Sugammadex 1.0 mg/kg (Sgx 1.0) Sugammadex 1.25 mg/kg (Sgx 1.25)
Neo 10 Neostigmine group: Different doses of neostigmine for reversal of shallow neuromuscular blockade	Drug: Neostigmine Neostigmine 10 µg/kg (Neo 10) Neostigmine 25 µg/kg (Neo 25) Neostigmine 40 µg/kg (Neo 40) Neostigmine 55 µg/kg (Neo 55) Neostigmine 70 µg/kg (Neo 70)
Neo 25 Neostigmine group: Different doses of neostigmine for reversal of shallow neuromuscular blockade	Drug: Neostigmine Neostigmine 10 µg/kg (Neo 10) Neostigmine 25 µg/kg (Neo 25) Neostigmine 40 µg/kg (Neo 40) Neostigmine 55 µg/kg (Neo 55) Neostigmine 70 µg/kg (Neo 70)
Neo 40 Neostigmine group: Different doses of neostigmine for reversal of shallow neuromuscular blockade	Drug: Neostigmine Neostigmine 10 µg/kg (Neo 10) Neostigmine 25 µg/kg (Neo 25) Neostigmine 40 µg/kg (Neo 40) Neostigmine 55 µg/kg (Neo 55) Neostigmine 70 µg/kg (Neo 70)
Neo 55 Neostigmine group: Different doses of neostigmine for reversal of shallow neuromuscular blockade	Drug: Neostigmine Neostigmine 10 µg/kg (Neo 10) Neostigmine 25 µg/kg (Neo 25) Neostigmine 40 µg/kg (Neo 40) Neostigmine 55 µg/kg (Neo 55) Neostigmine 70 µg/kg (Neo 70)
Neo 70 Neostigmine group: Different doses of neostigmine for reversal of shallow neuromuscular blockade	Drug: Neostigmine Neostigmine 10 µg/kg (Neo 10) Neostigmine 25 µg/kg (Neo 25) Neostigmine 40 µg/kg (Neo 40) Neostigmine 55 µg/kg (Neo 55) Neostigmine 70 µg/kg (Neo 70)
Saline Saline group: Saline as placebo	Drug: Saline Saline 0.9% (Saline)

Detailed Description:

Muscle relaxants are integral part of modern anesthesia. They optimize intubating conditions, reduce laryngeal trauma and improve operating conditions. Drawback is a possible pharmacological (muscle relaxing) effect of these drugs beyond the end of the operation (i.e. post-operative residual curarization: PORC). Reportedly about 30% of all patients who received muscle relaxants show signs of PORC when arriving in the post-anesthesia care unit. PORC comprises the risk of impaired post-operative fine motor and coordinative skills with a possible impairment of swallowing pharyngeal secretions with an increased risk of aspiration after extubation. Possible deleterious effects of this could be pneumonia, bronchitis, myocardial infarction, cardiac insufficiency, stroke or re-operation.

In order to avoid PORC patients with residual neuromuscular block receive a muscle relaxant antagonist from the anesthesiologist at the end of the operation. However, these drugs (neostigmine, pyridostigmine, etc.) from the class of cholinesterase inhibitors have unwanted effects such as bradycardia, increased gastro-intestinal motility, post-operative nausea and vomiting, salivation etc. To decrease these unwanted side effects cholinesterase inhibitors have to be given in combination with parasympatholyics e.g. atropine or glycopyrrolate with their own spectrum of unwanted side effects.

From October 2008 on, Sugammadex, a completely new reversal drug was introduced in to clinical practice. Sugammadex, is a modified γ-cyclodextrine able to specifically bind rocuronium (a steroidal muscle relaxant). The complex is eliminated via the kidneys. However, all studies so far have focussed on reversal of profound or deep neuromuscular blockade. This study is designed to compare recovery times after reversal of a residual neuromuscular block (TOF-ratio 0.2) with different doses of either the neostigmine or sugammadex.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

Patients receiving rocuronium for neuromuscular blockade under general anesthesia

Criteria

Inclusion Criteria:

Patients ASA physical status I - III
Patients over 18 years
Patients scheduled for general anesthesia with intubation using rocuronium
Patients having given informed consent to the study

Exclusion Criteria:

Anatomic and functional malformations with expected difficult intubation
Known or suspected neuromuscular disease
Significant hepatic or renal dysfunction
Known or suspected history or family history of disposition to malignant hyperthermia
Known or suspected allergy towards sugammadex, anesthetics, muscle relaxants, or other drugs used for general anesthesia
Use of drugs that interfere with muscle relaxants
Patients, included in another trial within the last 30 days
Patients, with legal guidant
Patients with contraindication towards the use of Sugammadex, neostigmine or glycopyrrolate
Patients, which have already participated in a sugammadex trial
Pregnant women (exclusion of pregnancy: postmenopausal status, negative β- HCG screen, status post tubal ligation)
Breastfeeding women

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01006720

Locations

Germany
Klinik für Anaesthesiologie, Klinikum rechts der Isar der Technischen Universität München
Munic, Bavaria, Germany, 81675

Sponsors and Collaborators

Technische Universität München

Investigators

Principal Investigator:

Heidrun Fink, PD Dr., MD

Klinik für Anaesthesiologie, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675 München

More Information

Publications:

Jones RK, Caldwell JE, Brull SJ, Soto RG. Reversal of profound rocuronium-induced blockade with sugammadex: a randomized comparison with neostigmine. Anesthesiology. 2008 Nov;109(5):816-24.

Pühringer FK, Rex C, Sielenkämper AW, Claudius C, Larsen PB, Prins ME, Eikermann M, Khuenl-Brady KS. Reversal of profound, high-dose rocuronium-induced neuromuscular blockade by sugammadex at two different time points: an international, multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial. Anesthesiology. 2008 Aug;109(2):188-97.

Flockton EA, Mastronardi P, Hunter JM, Gomar C, Mirakhur RK, Aguilera L, Giunta FG, Meistelman C, Prins ME. Reversal of rocuronium-induced neuromuscular block with sugammadex is faster than reversal of cisatracurium-induced block with neostigmine. Br J Anaesth. 2008 May;100(5):622-30. Epub 2008 Apr 2.

Responsible Party:	Technische Universität München
ClinicalTrials.gov Identifier:	NCT01006720 History of Changes
Other Study ID Numbers:	SUNDRO20, EudraCT number 2009-013499-29
Study First Received:	November 2, 2009
Last Updated:	December 12, 2012
Health Authority:	Germany: Ethics Commission

Keywords provided by Technische Universität München:

Residual neuromuscular block
post-operative residual curarization
PORC
sugammadex
neostigmine

Additional relevant MeSH terms:

Neostigmine
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cholinergic Agents

Neurotransmitter Agents
Physiological Effects of Drugs
Parasympathomimetics
Autonomic Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on May 21, 2013

Sugammadex and Neostigmine at Residual Neuromuscular Blockade (SUNDRO20)