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A Randomized Controlled Crossover Study Comparing Sugammadex and Placebo

Effect of Reversal of Neuromuscular Blockade on the Amplitude of Motor Evoked Potentials: A Randomized Controlled Crossover Study Comparing Sugammadex and Placebo

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03087513
Enrollment
40
Registered
2017-03-22
Start date
2018-02-05
Completion date
2020-04-30
Last updated
2020-06-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Posterior Cervical Decompression and Fusion

Keywords

Motor Evoked Potentials, Spine surgery, Muscle relaxants

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.

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.

Interventions

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.

DRUGPlacebo

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.

Sponsors

Merck Sharp & Dohme LLC
CollaboratorINDUSTRY
University Health Network, Toronto
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, 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.

Intervention model description

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

Eligibility

Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No

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)

Design outcomes

Primary

MeasureTime frameDescription
Changes Motor Evoked Potentials (MEPs) Amplitude at 3 MinutesBaseline and 3 minutes after the study interventionChanges 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

MeasureTime frameDescription
MEPs Amplitude Changes From Baseline at 9 MinutesBaseline to 9 minutesComparison of changes in MEP amplitudes from baseline at 9 minutes between sugammadex and placebo groups
MEPs Amplitude Changes in Both Sugammadex and Placebo GroupsBaseline to 6 minutesChanges in the amplitude of the MEPs from the baseline in the first dorsal interosseous muscle at 6 minutes
Patient MovementFrom 0 to 15 minutesNumber of patients moved and observed by the surgeon. From the study intervention to the surgeon observed patient movements
Surgical Grading of Relaxation of the Surgical Fieldapproximatelt 1 hour - 30 min during surgical exposure and 30 minutes during closureSurgical grading of relaxation of the surgical field as per the Likert-4 point surgical grading of surgical field. During surgical exposure and closure.

Countries

Canada

Participant flow

Recruitment details

Between February 2018 and April 2019, 73 posterior cervical spine patients screened from the preoperative assessment clinic of Toronto Western Hospital to identify eligible patients. First participant was enrolled on March 2018 and the last participant was enrolled on April 2019.

Pre-assignment details

40 participants received 10ml syringe containing Sugammadex (2mg/kg) in the first phase, followed by Placebo 10 ml in the second phase or 10ml syringe containing Placebo in the first phase, followed by 10 ml of Sugammadex (2mg/kg) in the second phase. Time interval of approximately 3 hours between initial and crossover arm. 2 Patients withdrawn

Participants by arm

ArmCount
Study Intervention
Initial Arm The study participants will receive10ml syringe containing Sugammadex (2mg/kg) in the first phase, followed by 10 ml of Placebo in the second phase. Cross-over Arm The study participants will receive10ml syringe containing Placebo in the first phase, followed by 10 ml of Sugammadex (2mg/kg) in the second phase.
38
Total38

Withdrawals & dropouts

PeriodReasonFG000
Second Intervention After 3 hr WashoutEquipment malfunction2

Baseline characteristics

CharacteristicStudy Intervention
Age, Customized
Age
60.8 Years
STANDARD_DEVIATION 11.1
Baseline Motor Evoked Potential amplitudes in both baseline and cross-over arms
Left FDI Placebo Group
377.1 micro volts
Baseline Motor Evoked Potential amplitudes in both baseline and cross-over arms
Left FDI Sugammedex Group
544.4 micro volts
Baseline Motor Evoked Potential amplitudes in both baseline and cross-over arms
Right FDI Placebo Group
418.7 micro volts
Baseline Motor Evoked Potential amplitudes in both baseline and cross-over arms
Right FDI Sugammedex Group
439.6 micro volts
Race and Ethnicity Not Collected— Participants
Sex: Female, Male
Female
21 Participants
Sex: Female, Male
Male
17 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 380 / 38
other
Total, other adverse events
0 / 380 / 38
serious
Total, serious adverse events
0 / 380 / 38

Outcome results

Primary

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

Time frame: Baseline and 3 minutes after the study intervention

Population: Data are presented as Median (IQR). MEP- Motor evoked potential, µV-microvolt, min-minute, 1Q- First quartile, 3Q-third quartile, FDI- first dorsal interosseous

ArmMeasureGroupValue (MEDIAN)
SugammadexChanges Motor Evoked Potentials (MEPs) Amplitude at 3 MinutesLeft FDI amplitude changes from baseline at 3 min652.9 micro volts
SugammadexChanges Motor Evoked Potentials (MEPs) Amplitude at 3 MinutesRight FDI amplitude changes from baseline at 3 min2153.4 micro volts
PlaceboChanges Motor Evoked Potentials (MEPs) Amplitude at 3 MinutesLeft FDI amplitude changes from baseline at 3 min20.6 micro volts
PlaceboChanges Motor Evoked Potentials (MEPs) Amplitude at 3 MinutesRight FDI amplitude changes from baseline at 3 min55 micro volts
Comparison: In total, 40 patients were randomised for the study. Data from 2 patients were excluded as the crossover arm could not be completed due to intraoperative MEP change (n=1) and the equipment malfunction (n=1). The data distributions were tested for normality with the Kolmogorov-Smirnov test.p-value: <0.01Mixed Models Analysis
Secondary

MEPs Amplitude Changes From Baseline at 9 Minutes

Comparison of changes in MEP amplitudes from baseline at 9 minutes between sugammadex and placebo groups

Time frame: Baseline to 9 minutes

Population: Data are presented as Median (IQR). MEP- Motor evoked potential, µV-microvolt, min-minute, 1Q- First quartile, 3Q-third quartile, FDI- first dorsal interosseous

ArmMeasureGroupValue (MEDIAN)
SugammadexMEPs Amplitude Changes From Baseline at 9 MinutesLeft FDI894.9 micro volts
SugammadexMEPs Amplitude Changes From Baseline at 9 MinutesRight FDI1256.3 micro volts
PlaceboMEPs Amplitude Changes From Baseline at 9 MinutesLeft FDI105.5 micro volts
PlaceboMEPs Amplitude Changes From Baseline at 9 MinutesRight FDI337.2 micro volts
Secondary

MEPs Amplitude Changes in Both Sugammadex and Placebo Groups

Changes in the amplitude of the MEPs from the baseline in the first dorsal interosseous muscle at 6 minutes

Time frame: Baseline to 6 minutes

Population: Data are presented as Median (IQR). MEP- Motor evoked potential, µV-microvolt, min-minute, 1Q- First quartile, 3Q-third quartile, FDI- first dorsal interosseous

ArmMeasureGroupValue (MEDIAN)
SugammadexMEPs Amplitude Changes in Both Sugammadex and Placebo GroupsLeft FDI646.4 micro volts
SugammadexMEPs Amplitude Changes in Both Sugammadex and Placebo GroupsRight FDI1609.3 micro volts
PlaceboMEPs Amplitude Changes in Both Sugammadex and Placebo GroupsLeft FDI84.3 micro volts
PlaceboMEPs Amplitude Changes in Both Sugammadex and Placebo GroupsRight FDI201.9 micro volts
Secondary

Patient Movement

Number of patients moved and observed by the surgeon. From the study intervention to the surgeon observed patient movements

Time frame: From 0 to 15 minutes

ArmMeasureValue (NUMBER)
SugammadexPatient Movement6 participants
PlaceboPatient Movement0 participants
Secondary

Surgical Grading of Relaxation of the Surgical Field

Surgical grading of relaxation of the surgical field as per the Likert-4 point surgical grading of surgical field. During surgical exposure and closure.

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

ArmMeasureCategoryValue (COUNT_OF_PARTICIPANTS)
SugammadexSurgical Grading of Relaxation of the Surgical FieldGood or optimal condition31 Participants
SugammadexSurgical Grading of Relaxation of the Surgical FieldAcceptable6 Participants
SugammadexSurgical Grading of Relaxation of the Surgical FieldPoor1 Participants
PlaceboSurgical Grading of Relaxation of the Surgical FieldPoor0 Participants
PlaceboSurgical Grading of Relaxation of the Surgical FieldGood or optimal condition35 Participants
PlaceboSurgical Grading of Relaxation of the Surgical FieldAcceptable3 Participants

Source: ClinicalTrials.gov · Data processed: Feb 22, 2026