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

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)

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:

1. 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.
2. 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.

Study Overview

• Status: Unknown
• Conditions: Postoperative Residual Curarization; Neuromuscular Block
• Intervention / Treatment: Drug: Sugammadex

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 144
• Phase: Phase 4

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: The Hospital of Vestfold

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2018
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: October 17, 2017
• First Submitted That Met QC Criteria: March 4, 2018
• First Posted (Actual): March 9, 2018

Study Record Updates

• Last Update Posted (Actual): May 30, 2018
• Last Update Submitted That Met QC Criteria: May 27, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Delayed Emergence from Anesthesia
• Other Study ID Numbers: SIVAA01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No