Reversal With Low Doses of Sugammadex in Patients Undergoing Non-cardiac Surgery

Study Overview
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Brief Summary
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Neuromuscular blocking agents (NMBA) are among the most commonly used drugs during general anesthesia and may induce complete muscle paralysis.They are used clinically to facilitate endotracheal intubation and to optimize surgical working conditions. Incomplete recovery from non-depolarising NMBAs continues to be a common problem in modern postoperative care unit and is associated with significant risk of microaspiration and hypoventilation which leads to pulmonary complications.Recently effective reversal of neuromuscular blockade has been described by use of lower dose of sugammadex the recommended without providing adequate answer to whether the lower dose is safe enough to avoid recurrent block. Hypotheses: Administration of sugammadex 0.25 mg/kg at TOF ratio 0.3 will successfully reverse (TOF=0.9) rocuronium induced neuromuscular block within 10 min. Recurrent block (TOF ratio < 0.9) does not occur after reversal with low dose sugammadex 0.25 mg/kg. The primary objective of this trial is to assess the dose-response characteristics of sugammadex in reversing rocuronium induced neuromuscular block and to identify the minimal effective dose Secondary objective is to assess the safety of different doses of sugammadex (recurrent block (TOF ratio < 0.9) after reversal and the occurrence of adverse reactions) Sugammadex is a very expensive drug which limits its use i anaesthesia department. By optimising drug dosage it may have economic impact and contribute to a wider use of sugammadex to reverse neuromuscular block before extubation and thus avoid incomplete recovery. This may lead to less risk for postoperative pulmonary complications and thereby reduce morbidity and mortality after surgery.

Detailed Description
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Doses of study drug will be 0 mg/kg Ideal Body Weight (IBW), 0.25 mg/kg IBW, 0.50 mg/kg IBW, 1.0 mg/kg IBW and 2.0 mg/kg IBW. TOF will be measured every 10th second until full reversal.

Official Title
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A Randomized Double Blind Trial Comparing Reversal With Low Doses Of Sugammadex aFter Rocuronium-induced Neuromuscular Block Under General Anesthesia in Patients Undergoing Non-cardiac Surgery(TOF TRIAL)

Conditions
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Postoperative Residual Curarization, Neuromuscular Block

Intervention / Treatment
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* Drug: Sugammadex


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient, both genders, undergoing any elective in-hospital surgical procedure under general anesthesia requiring rocuronium neuromuscular block. ASA I-IV Signed informed consent Exclusion Criteria: Patient less than 18 years of age Patient participating in another clinical study which could interfere with TOF trial. Patient with neuromuscular disease Patient from ICU BMI > 30.0 kg/m2 Patient scheduled for local or regional anesthesia only Patient undergoing general anesthesia without rocuronium Patient with hypersensitivity to NMBAs or sugammadex. Also hypersensitivity to any active substance or to any of the following excipient: Hydrochloric acid 3.7% (to adjust pH) and/or sodium hydroxide (to adjust pH) Water for injections . Renal dysfunction (GFR<30 mL/min/1,73m2) Hepatic dysfunction Patient who have received sugammadex in the last 24 h. Pregnant or breastfeeding woman. Women in childbearing age must have a negative pregnant test before inclusion. Bradycardia (puls <40) Hypotension (Systolic BP <90 mmHg)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Sugammadex 0 mg/kg<br>Placebo NaCl 0,9% | Drug: Sugammadex<br>* Dose-response<br>|
| Active Comparator: Sugammadex 0,25 mg/kg<br>Sugammadex 0.25 mg/kg IBW | Drug: Sugammadex<br>* Dose-response<br>|
| Active Comparator: Sugammadex 0,5 mg/kg<br>Sugammadex 0.50 mg/kg IBW | Drug: Sugammadex<br>* Dose-response<br>|
| Active Comparator: Sugammadex 1mg/kg<br>Sugammadex 1.0 mg/kg IBW | Drug: Sugammadex<br>* Dose-response<br>|
| Active Comparator: Sugammadex 2mg/kg<br>Sugammadex 2 mg/kg IBW | Drug: Sugammadex<br>* Dose-response<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The time from study drug administration to reaching a TOF ratio of 0.9. |  | 10 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patient with reoccurrence of neuromuscular block after initial reversal to TOF ratio 0.9. |  | 20 minutes | 
| Number of patients with adverse reactions in each group | Adverse reactions (anaphylactic reaction, flushing, urticaria, erythematous rash, (severe) hypotension (BPsyst> 75 mmHg), tachycardia (heart rate> 120 beats/min), bradycardia (heart rate <40 beats/min), swelling of tongue, swelling of pharynx, bronchospasm) | until discharge - 3 days |