Sugammadex and Neostigmine at Shallow Neuromuscular Blockade

Study Overview
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Brief Summary
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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
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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.

Official Title
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Dose Finding Study for Sugammadex and Neostigmine at Residual Neuromuscular Blockade (T4/T1 = 0.5)

Conditions
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Neuromuscular Block

Intervention / Treatment
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* Drug: Sugammadex, Neostigmine, Saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sugammadex<br>Sugammadex in doses: 0 (placebo), 0.0625, 0.125, 0.25, 0.5 and 1 mg/kg | Drug: Sugammadex, Neostigmine, Saline<br>* 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)<br>|
| Active Comparator: Neostigmine<br>Neostigmine in doses: 0 (placebo), 5, 8, 15, 25, 40 mg/kg | Drug: Sugammadex, Neostigmine, Saline<br>* 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)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to TOF-ratio 0.9 following the investigational drug |  | Regular anesthesia time, approximately 1 hour | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Residual neuromuscular block, post-operative residual curarization, PORC, sugammadex, neostigmine, Shallow neuromuscular block (TOF-ratio of 0.5)