Sugammadex and Neostigmine at Shallow Neuromuscular Blockade (SUNDRO)

• ClinicalTrials.gov Identifier: NCT00895609
• Recruitment Status: Completed
• First Posted: May 8, 2009
• Last Update Posted: March 19, 2013
• Sponsor: Technische Universität München
• Information provided by: Technische Universität München

Tracking Information

• First Submitted Date: April 29, 2009
• First Posted Date: May 8, 2009
• Last Update Posted Date: March 19, 2013
• Study Start Date: March 2009
• Actual Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 7, 2009): Time to TOF-ratio 0.9 following the investigational drug [ Time Frame: Regular anesthesia time, approximately 1 hour ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Sugammadex and Neostigmine at Shallow Neuromuscular Blockade
• Official Title: Dose Finding Study for Sugammadex and Neostigmine at Residual Neuromuscular Blockade (T4/T1 = 0.5)
• Brief Summary: This study is designed to compare recovery times after reversal of a residual neuromuscular block (TOF-ratio 0.5) with different doses of either neostigmine or sugammadex.

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 anesthetist 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 gamma-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 0.5) with different doses of either the neostigmine or sugammadex.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Neuromuscular Block

Intervention

Drug: Sugammadex, Neostigmine, Saline

Single intravenous injection of either:

Sugammadex 0.0625 mg/kg (Sgx 0.0625) Sugammadex 0.125 mg/kg (Sgx 0.125) Sugammadex 0.25 mg/kg (Sgx 0.25) Sugammadex 0.5 mg/kg (Sgx 0.5) Sugammadex 1.0 mg/kg (Sgx 1.0) Neostigmine 5 mg/kg (Neo 5) Neostigmine 8 mg/kg (Neo 8) Neostigmine 15 mg/kg (Neo 15) Neostigmine 25 mg/kg (Neo 25) Neostigmine 40 mg/kg (Neo 40) Saline 0.9% (Saline)

Study Arms

• Experimental: Sugammadex
  Sugammadex in doses: 0 (placebo), 0.0625, 0.125, 0.25, 0.5 and 1 mg/kg
  Intervention: Drug: Sugammadex, Neostigmine, Saline
• Active Comparator: Neostigmine
  Neostigmine in doses: 0 (placebo), 5, 8, 15, 25, 40 mg/kg
  Intervention: Drug: Sugammadex, Neostigmine, Saline

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. doi: 10.1097/ALN.0b013e31818a3fee.
• 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. doi: 10.1097/ALN.0b013e31817f5bc7.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 12, 2012): 99
• Original Enrollment: Not Provided
• Actual Study Completion Date: August 2009
• Actual Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients ASA physical status I - III
• Patients between 18 and 64 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 64 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT00895609
• Other Study ID Numbers: SUNDRO
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Not Provided
• Study Sponsor: Technische Universität München
• Collaborators: Not Provided

Investigators

• Principal Investigator: Manfred Blobner, MD; Klinik für Anaesthesiologie, Klinikum rechts der Isar der Technischen Universität München

• PRS Account: Technische Universität München
• Verification Date: March 2013