A Randomized Controlled Crossover Study Comparing Sugammadex and Placebo

• ClinicalTrials.gov Identifier: NCT03087513
• Recruitment Status: Completed
• First Posted: March 22, 2017
• Results First Posted: June 1, 2020
• Last Update Posted: June 17, 2020
• Sponsor: University Health Network, Toronto
• Collaborator: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Lashmi Venkatraghavan, University Health Network, Toronto

Study Description

Brief Summary:

Intraoperative monitoring of the motor evoked potentials has been shown to be both a sensitive and specific indicator for detecting intraoperative neurological injuries during spine surgery.(Fehlings, Brodke et al. 2010) It is utilized whenever there is risk for injury of nerve roots or the spinal cord during the procedure.

Anesthetic agents, especially the inhaled volatile anesthetics and muscle relaxants, are con-founders for motor evoked potential monitoring as they have deleterious effects on the amplitude of motor evoked potentials.(Sekimoto, Nishikawa et al. 2006) Hence, total intravenous anesthesia with no intraoperative muscle relaxants, are the standard anesthetic technique for these surgeries.

Muscle relaxants are usually required during the induction of anesthesia and endotracheal intubation of larynx. Current practice is to wait for the resolution of residual neuromuscular blockade before the motor evoked potential recordings (MEP) are initiated and this makes it difficult to assess if there was any neurological injury associated with positioning of the patient. A previous case series has shown that reversal of muscle relaxant can improve the amplitude of MEPs.(Batistaki, Papadopoulos et al. 2012) The aim of this study is to perform a randomized controlled trial to study the changes in motor evoked potential amplitudes comparing sugammadex and placebo.

Condition or disease	Intervention/treatment	Phase
Posterior Cervical Decompression and Fusion	Drug: Sugammadex Injection [Bridion]; Drug: Placebo	Phase 4

Detailed Description:

Motor evoked potential monitoring is a well-established and safe intervention to assist in prevention of intraoperative injury during spine surgery.(Schwartz, Sestokas et al. 2011) Patients with cervical myelopathy often present with neurological deficits and recording of the motor evoked potentials are often challenging in these patients. In addition, anesthetic agents especially muscle relaxants can abolish the motor response making it difficult to know when the baseline MEP can be recorded.

The usual anesthetic practice for patients undergoing posterior cervical spine surgery is to administer muscle relaxation to aid intubation at the start of the case . The neuromuscular blockade is then allowed to wear off and the neurophysiologist will attempt to record their baseline motor evoked potentials during or just prior to surgical exposure.

The issues with this current technique are;

1. Patients cannot be monitored for neurological changes during their transfer into the prone position
2. There is likely residual neuromuscular blockade decreasing the amplitude of motor evoked potentials.

Investigators plan to perform a randomized controlled cross-over trial comparing the change in MEP amplitudes with administration of sugammadex or placebo. This will be performed on at risk patients (e.g. cervical myelopathy) undergoing posterior cervical spine surgery where MEPs can be more difficult to attain but of higher utility.

The purpose of this study is to determine if reversal of residual neuromuscular blockade with Sugammadex can increase the amplitude of the motor evoked potentials.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Randomized controlled crossover trial comparing the change in MEP amplitudes with administration of sugammadex or placebo.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description

This is a randomized blinded study where the administering anesthetist, surgeon and neurophysiologists will be blinded to the intervention.

Further, a blinded research assistant will perform assessment, data collection, and analysis of neurophysiology data attained.

• Primary Purpose: Prevention
• Official Title: Effect of Reversal of Neuromuscular Blockade on the Amplitude of Motor Evoked Potentials: A Randomized Controlled Crossover Study Comparing Sugammadex and Placebo
• Actual Study Start Date: February 5, 2018
• Actual Primary Completion Date: December 30, 2019
• Actual Study Completion Date: April 30, 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Initial Arm; The study participants will receive either Sugammadex (2 mg/kg in 10 ml 0.9% normal saline) or placebo (10 ml of 0.9% normal saline).	Drug: Sugammadex Injection [Bridion]; The study participants will receive 10 ml syringe containing Sugammadex (2mg/kg) in the first phase followed by Placebo 10 ml syringe containing of 0.9% of normal saline in the second phase.; Other Name: Sugammadex; Drug: Placebo; The study participants will receive Placebo 10 ml syringe containing of 0.9% of normal saline in the first phase followed by 10 ml syringe containing Sugammadex (2mg/kg) in the second phase.; Other Name: Normal Saline
Active Comparator: Crossover Arm; The study participants will receive the study medication that was not given in the initial arm (either Sugammadex (2 mg/kg in 10 ml 0.9% normal saline) or placebo (10 ml of 0.9% normal saline) .	Drug: Sugammadex Injection [Bridion]; The study participants will receive 10 ml syringe containing Sugammadex (2mg/kg) in the first phase followed by Placebo 10 ml syringe containing of 0.9% of normal saline in the second phase.; Other Name: Sugammadex; Drug: Placebo; The study participants will receive Placebo 10 ml syringe containing of 0.9% of normal saline in the first phase followed by 10 ml syringe containing Sugammadex (2mg/kg) in the second phase.; Other Name: Normal Saline

Outcome Measures

Primary Outcome Measures :

1. Changes Motor Evoked Potentials (MEPs) Amplitude at 3 Minutes [ Time Frame: Baseline and 3 minutes after the study intervention ]
   Changes in the amplitude of the Motor Evoked Potentials from the baseline in the first dorsal interosseous muscle at 3 minutes in sugammadex group compared to placebo group

Secondary Outcome Measures :

1. MEPs Amplitude Changes in Both Sugammadex and Placebo Groups [ Time Frame: Baseline to 6 minutes ]
   Changes in the amplitude of the MEPs from the baseline in the first dorsal interosseous muscle at 6 minutes
2. MEPs Amplitude Changes From Baseline at 9 Minutes [ Time Frame: Baseline to 9 minutes ]
   Comparison of changes in MEP amplitudes from baseline at 9 minutes between sugammadex and placebo groups
3. Patient Movement [ Time Frame: From 0 to 15 minutes ]
   Number of patients moved and observed by the surgeon. From the study intervention to the surgeon observed patient movements
4. Surgical Grading of Relaxation of the Surgical Field [ Time Frame: approximatelt 1 hour - 30 min during surgical exposure and 30 minutes during closure ]

   Surgical grading of relaxation of the surgical field as per the Likert-4 point surgical grading of surgical field.

   During surgical exposure and closure.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• All adult patients aged 18-80 years with American Society of Anesthesiologist (ASA) classification I-III undergoing cervical spine surgery in the prone position with intraoperative motor evoked potential monitoring.
• Operation time greater than 3 hours

Exclusion Criteria:

• Allergy to propofol or documented egg allergy
• Known allergy to sugammadex
• Severe renal dysfunction (EGFR<30)
• British Research Medical Council (BRMC) motor grading <3 in any peripheral muscle group preoperatively. This is inability to move the muscle group against gravity.
• Surgical requirement of strict muscle relaxation for surgical exposure
• Lack of informed consent
• Pregnancy
• Loss of MEP signals during washout period (or intraoperative spinal cord injury resulting in irreversible loss of MEP)

Contacts and Locations

Locations

Canada, Ontario

TWH/UHN

Toronto, Ontario, Canada, M5T 2S8

Sponsors and Collaborators

University Health Network, Toronto

Merck Sharp & Dohme Corp.

Investigators

• Principal Investigator: Lashmi Venkatraghavan; University Health Network, Toronto

  Study Documents (Full-Text)

Documents provided by Lashmi Venkatraghavan, University Health Network, Toronto:

Study Protocol and Statistical Analysis Plan  [PDF] April 20, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Venkatraghavan L, Royan N, Boyle SL, Dinsmore M, Lu N, Cushman K, Massicotte EM, Prabhu A. Effect of reversal of residual neuromuscular blockade on the amplitude of motor evoked potentials: a randomized controlled crossover study comparing sugammadex and placebo. Neurol Sci. 2022 Jan;43(1):615-623. doi: 10.1007/s10072-021-05318-8. Epub 2021 May 26.

• Responsible Party: Lashmi Venkatraghavan, Associate Professor, Department of Anesthesia, Toronto Western Hospital, Toronto, Canada, University Health Network, Toronto
• ClinicalTrials.gov Identifier: NCT03087513
• Other Study ID Numbers: 16-5926-B
• First Posted: March 22, 2017
• Results First Posted: June 1, 2020
• Last Update Posted: June 17, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Lashmi Venkatraghavan, University Health Network, Toronto:

Motor Evoked Potentials, Spine surgery, Muscle relaxants