Sugammadex and Neostigmine at Residual Neuromuscular Blockade (SUNDRO20)

Dose Finding Study for Sugammadex and Neostigmine at Residual Neuromuscular Blockade (T4/T1 = 0.2)

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.

Study Overview

• Status: Completed
• Conditions: Residual Neuromuscular Block (TOF-ratio of 0.2)
• Intervention / Treatment: Drug: Sugammadex; Drug: Neostigmine; Drug: 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.

• Study Type: Observational
• Enrollment (Actual): 99

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients receiving rocuronium for neuromuscular blockade under general anesthesia

Description

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

Study Plan

How is the study designed?

Design Details

• Time Perspectives: Prospective

Number of groups / cohorts

11

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to TOF-ratio 0.9 following the investigational drug	Regular anesthesia time, approximately 1.5 hours

Collaborators and Investigators

• Sponsor: Technical University of Munich
• Investigators: Principal Investigator: Heidrun Fink, PD Dr., MD, Klinik für Anaesthesiologie, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675 München

Publications and helpful links

General Publications

• Puhringer FK, Rex C, Sielenkamper 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. doi: 10.1097/ALN.0b013e31817f5bc7.
• 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. doi: 10.1097/ALN.0b013e31818a3fee.
• 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. doi: 10.1093/bja/aen037. Epub 2008 Apr 2.
• Kaufhold N, Schaller SJ, Stauble CG, Baumuller E, Ulm K, Blobner M, Fink H. Sugammadex and neostigmine dose-finding study for reversal of residual neuromuscular block at a train-of-four ratio of 0.2 (SUNDRO20)dagger, Br J Anaesth. 2016 Feb;116(2):233-40. doi: 10.1093/bja/aev437.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: November 2, 2009
• First Submitted That Met QC Criteria: November 2, 2009
• First Posted (Estimate): November 3, 2009

Study Record Updates

• Last Update Posted (Estimate): December 13, 2012
• Last Update Submitted That Met QC Criteria: December 12, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: sugammadex; Residual neuromuscular block; post-operative residual curarization; PORC; neostigmine
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Delayed Emergence from Anesthesia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Enzyme Inhibitors; Cholinesterase Inhibitors; Parasympathomimetics; Neostigmine
• Other Study ID Numbers: SUNDRO20; EudraCT number 2009-013499-29