A Randomized Controlled Crossover Study Comparing Sugammadex and Placebo

NCT03087513 | Completed Phase 4 Results

• 1 other identifier: 16-5926-B
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Posterior Cervical Decompression and Fusion

Keywords

Motor Evoked Potentials, Spine surgery, Muscle relaxants

Outcome Measures

Primary Outcomes (1)

• Changes Motor Evoked Potentials (MEPs) Amplitude at 3 Minutes

  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

  Baseline and 3 minutes after the study intervention

Secondary Outcomes (4)

• MEPs Amplitude Changes in Both Sugammadex and Placebo Groups

  Baseline to 6 minutes

• MEPs Amplitude Changes From Baseline at 9 Minutes

  Baseline to 9 minutes

• Patient Movement

  From 0 to 15 minutes

• Surgical Grading of Relaxation of the Surgical Field

  approximatelt 1 hour - 30 min during surgical exposure and 30 minutes during closure

Study Arms (2)

Initial Arm

ACTIVE COMPARATOR

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]; Drug: Placebo

Crossover Arm

ACTIVE COMPARATOR

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]; Drug: Placebo

Interventions

Sugammadex Injection [Bridion] DRUG

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.

Also known as: Sugammadex

Crossover Arm; Initial Arm

Placebo DRUG

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.

Also known as: Normal Saline

Crossover Arm; Initial Arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

TWH/UHN

Toronto, Ontario, M5T 2S8, Canada

Location

Related Publications (1)

• 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.

  PMID: 34041634 DERIVED

MeSH Terms

Conditions

Muscle Hypotonia

Interventions

Sugammadex; Saline Solution

Condition Hierarchy (Ancestors)

Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

gamma-Cyclodextrins; Cyclodextrins; Macrocyclic Compounds; Polycyclic Compounds; Dextrins; Starch; Glucans; Polysaccharides; Carbohydrates; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Study Coordinator
• Organization: Toronto Western Hospital/University Health Network

emad.alazazi@uhnresearch.ca

416-603-5800

Study Officials

• Lashmi Venkatraghavan

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Department of Anesthesia, Toronto Western Hospital, Toronto, Canada

Model Details: Randomized controlled crossover trial comparing the change in MEP amplitudes with administration of sugammadex or placebo.

Study Record Dates

• First Submitted: March 6, 2017
• First Posted: March 22, 2017
• Study Start: February 5, 2018
• Primary Completion: December 30, 2019
• Study Completion: April 30, 2020
• Last Updated: June 17, 2020
• Results First Posted: June 1, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)