Trial Outcomes & Findings for Observational Study to Evaluate the Current Neuromuscular Monitoring Practice Used After Different Types of Surgery, for Which Neuromuscular Blocking Agents Were Used, With or Without Blocking Reversal (P06556) (NCT NCT01213264)

NCT ID: NCT01213264

Last Updated: 2015-03-17

Results Overview

Neuromuscular function assessment was performed according to routine anesthesiology practice. This typically involves application of repetitive Train-Of-Four (TOF) electrical stimulations to the ulnar nerve and assessment of twitch response at the adductor pollicis muscle. The TOF-ratio, expressed as a decimal from 0.0 up to 1.0, is the ratio of the magnitude of the fourth twitch (T4) to that of the first twitch (T1). The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade. The TOF-ratio was measured at the time of post-surgical extubation. TOF-ratio at time of extubation was to be recorded for each participant, if available, irrespective of the criteria used to make the decision to extubate the participant. TOF-ratio \<0.9 at extubation is considered to indicate a high risk for development of postoperative residual curarization (i.e, residual neuromuscular blockade), which can result in respiratory complications.

Recruitment status

COMPLETED

Target enrollment

659 participants

Primary outcome timeframe

At extubation (approximately <1 to 125 minutes after end of surgery)

Results posted on

2015-03-17

Participant Flow

Participant milestones

Participant milestones
Measure
Spontaneous Reversal
Participants whose reversal from neuromuscular blockade (NMB) was spontaneous (no reversal agent used)
Sugammadex
Participants administered sugammadex for NMB reversal
Other Reversal Agents
Participants administered any other agent (other than sugammadex) for NMB reversal
Overall Study
STARTED
155
177
327
Overall Study
COMPLETED
153
175
321
Overall Study
NOT COMPLETED
2
2
6

Reasons for withdrawal

Reasons for withdrawal
Measure
Spontaneous Reversal
Participants whose reversal from neuromuscular blockade (NMB) was spontaneous (no reversal agent used)
Sugammadex
Participants administered sugammadex for NMB reversal
Other Reversal Agents
Participants administered any other agent (other than sugammadex) for NMB reversal
Overall Study
Adverse Event
1
0
0
Overall Study
Lost to Follow-up
1
2
6

Baseline Characteristics

Observational Study to Evaluate the Current Neuromuscular Monitoring Practice Used After Different Types of Surgery, for Which Neuromuscular Blocking Agents Were Used, With or Without Blocking Reversal (P06556)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Spontaneous Reversal
n=155 Participants
Participants whose reversal from NMB was spontaneous (no reversal agent used)
Sugammadex
n=177 Participants
Participants administered sugammadex for NMB reversal
Other Reversal Agents
n=327 Participants
Participants administered any other agent (other than sugammadex) for NMB reversal
Total
n=659 Participants
Total of all reporting groups
Age, Continuous
41.7 years
STANDARD_DEVIATION 13.7 • n=5 Participants
45.3 years
STANDARD_DEVIATION 13.6 • n=7 Participants
42.7 years
STANDARD_DEVIATION 12.7 • n=5 Participants
43.2 years
STANDARD_DEVIATION 13.2 • n=4 Participants
Sex: Female, Male
Female
109 Participants
n=5 Participants
106 Participants
n=7 Participants
210 Participants
n=5 Participants
425 Participants
n=4 Participants
Sex: Female, Male
Male
46 Participants
n=5 Participants
71 Participants
n=7 Participants
117 Participants
n=5 Participants
234 Participants
n=4 Participants

PRIMARY outcome

Timeframe: At extubation (approximately <1 to 125 minutes after end of surgery)

Population: Evaluable participants with TOF-ratio measurement at time of extubation

Neuromuscular function assessment was performed according to routine anesthesiology practice. This typically involves application of repetitive Train-Of-Four (TOF) electrical stimulations to the ulnar nerve and assessment of twitch response at the adductor pollicis muscle. The TOF-ratio, expressed as a decimal from 0.0 up to 1.0, is the ratio of the magnitude of the fourth twitch (T4) to that of the first twitch (T1). The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade. The TOF-ratio was measured at the time of post-surgical extubation. TOF-ratio at time of extubation was to be recorded for each participant, if available, irrespective of the criteria used to make the decision to extubate the participant. TOF-ratio \<0.9 at extubation is considered to indicate a high risk for development of postoperative residual curarization (i.e, residual neuromuscular blockade), which can result in respiratory complications.

Outcome measures

Outcome measures
Measure
Spontaneous Reversal
n=137 Participants
Participants whose reversal from NMB was spontaneous (no reversal agent used)
Sugammadex
n=175 Participants
Participants administered sugammadex for NMB reversal
Other Reversal Agents
n=318 Participants
Participants administered any other agent (other than sugammadex) for NMB reversal
Number of Participants With a Train-Of-Four (TOF)-Ratio <0.9 at Extubation
55 participants
17 participants
95 participants

PRIMARY outcome

Timeframe: From end of surgery (end of last stitch) to extubation (duration of approximately <1 to 62 minutes)

Population: Evaluable participants with TOF-ratio measurement at time of extubation and available procedure duration data. Three sugammadex participants with duration from end of surgery to extubation \>1 hour were excluded from analysis; delay of extubation was considered due to factors unrelated to administration of sugammadex.

This measure is the duration from the last surgical wound stitch to the post-surgical extubation of the participant. The time of extubation was to be recorded for each participant, irrespective of the criteria used to make the decision to extubate the participant. Data are presented by TOF-ratio \<0.9 and ≥0.9 at extubation. The TOF-ratio is a measure of neuromuscular function ranging from 0.0 to 1.0. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade. TOF-ratio \<0.9 at extubation is considered to indicate a high risk for development of postoperative residual curarization (i.e, residual neuromuscular blockade), which can result in respiratory complications.

Outcome measures

Outcome measures
Measure
Spontaneous Reversal
n=137 Participants
Participants whose reversal from NMB was spontaneous (no reversal agent used)
Sugammadex
n=172 Participants
Participants administered sugammadex for NMB reversal
Other Reversal Agents
n=318 Participants
Participants administered any other agent (other than sugammadex) for NMB reversal
Time From End of Surgery (End of Last Stitch) to Extubation
TOF-ratio <0.9 at extubation (N=55, 17, 95)
12.80 minutes
Standard Deviation 11.54
8.82 minutes
Standard Deviation 5.16
11.76 minutes
Standard Deviation 7.14
Time From End of Surgery (End of Last Stitch) to Extubation
TOF-ratio ≥0.9 at extubation (N=82, 155, 223)
9.73 minutes
Standard Deviation 7.96
10.01 minutes
Standard Deviation 7.28
12.20 minutes
Standard Deviation 6.97

PRIMARY outcome

Timeframe: Day of surgery (Day 1)

Population: All study participants who received a neuromuscular blocking agent (NMBA) or NMB-reversal agent

The type of surgical procedure performed in each study participant was recorded.

Outcome measures

Outcome measures
Measure
Spontaneous Reversal
n=659 Participants
Participants whose reversal from NMB was spontaneous (no reversal agent used)
Sugammadex
Participants administered sugammadex for NMB reversal
Other Reversal Agents
Participants administered any other agent (other than sugammadex) for NMB reversal
Type of Surgical Procedure Performed in Study Participants
cholecystectomy
129 participants
Type of Surgical Procedure Performed in Study Participants
nasal septal operation
47 participants
Type of Surgical Procedure Performed in Study Participants
thyroidectomy
36 participants
Type of Surgical Procedure Performed in Study Participants
intervertebral disc operation
34 participants
Type of Surgical Procedure Performed in Study Participants
hysterectomy
28 participants
Type of Surgical Procedure Performed in Study Participants
other surgical procedure
385 participants

PRIMARY outcome

Timeframe: At administration of NMB-reversal agent (up to approximately 395 minutes after start of surgery)

Population: All study participants who received an NMBA or NMB-reversal agent

For all participants who received an NMB-reversal agent, the specific agent administered was recorded.

Outcome measures

Outcome measures
Measure
Spontaneous Reversal
n=659 Participants
Participants whose reversal from NMB was spontaneous (no reversal agent used)
Sugammadex
Participants administered sugammadex for NMB reversal
Other Reversal Agents
Participants administered any other agent (other than sugammadex) for NMB reversal
Type of NMB-reversal Agent Administered to Study Participants
neostigmine
327 participants
Type of NMB-reversal Agent Administered to Study Participants
sugammadex
177 participants
Type of NMB-reversal Agent Administered to Study Participants
NMB-reversal agent not administered
155 participants

SECONDARY outcome

Timeframe: Post-surgical period (up to approximately 24 hours post-surgery)

Population: Evaluable participants who received an NMB-reversal agent and had available procedure duration data. Participants in the Spontaneous Reversal group did not receive any NMB-reversal agents and therefore were not included in this analysis.

This measure is the duration from NMB-reversal agent administration to dismissal of the participant from the Operating Room. The time of dismissal from the Operating Room was to be recorded for each participant, irrespective of the criteria used to make the decision to dismiss the participant.

Outcome measures

Outcome measures
Measure
Spontaneous Reversal
n=124 Participants
Participants whose reversal from NMB was spontaneous (no reversal agent used)
Sugammadex
n=194 Participants
Participants administered sugammadex for NMB reversal
Other Reversal Agents
Participants administered any other agent (other than sugammadex) for NMB reversal
Time From NMB-reversal Agent Administration to Operating Room Dismissal
15.90 minutes
Standard Deviation 14.96
40.46 minutes
Standard Deviation 109.9

SECONDARY outcome

Timeframe: Post-surgical and recovery period (up to approximately 170 hours post-surgery)

Population: Evaluable participants who received an NMB-reversal agent and had available procedure duration data. Participants in the Spontaneous Reversal group did not receive any NMB-reversal agents and therefore were not included in this analysis.

This measure is the duration from NMB-reversal agent administration to dismissal of the participant from the Recovery Room. The time of dismissal from the Recovery Room was to be recorded for each participant, irrespective of the criteria used to make the decision to dismiss the participant.

Outcome measures

Outcome measures
Measure
Spontaneous Reversal
n=130 Participants
Participants whose reversal from NMB was spontaneous (no reversal agent used)
Sugammadex
n=199 Participants
Participants administered sugammadex for NMB reversal
Other Reversal Agents
Participants administered any other agent (other than sugammadex) for NMB reversal
Time From NMB-reversal Agent Administration to Recovery Room Dismissal
630.5 minutes
Standard Deviation 1070
619.2 minutes
Standard Deviation 1348

Adverse Events

Spontaneous Reversal

Serious events: 2 serious events
Other events: 21 other events
Deaths: 0 deaths

Sugammadex

Serious events: 3 serious events
Other events: 23 other events
Deaths: 0 deaths

Other Reversal Agents

Serious events: 2 serious events
Other events: 40 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Spontaneous Reversal
n=155 participants at risk
Participants whose reversal from NMB was spontaneous (no reversal agent used)
Sugammadex
n=177 participants at risk
Participants administered sugammadex for NMB reversal
Other Reversal Agents
n=327 participants at risk
Participants administered any other agent (other than sugammadex) for NMB reversal
Cardiac disorders
bradyarrythmia
0.00%
0/155
0.56%
1/177 • Number of events 1
0.00%
0/327
Immune system disorders
Type I hypersensitivity
0.00%
0/155
0.56%
1/177 • Number of events 1
0.00%
0/327
Infections and infestations
pneumonia
0.00%
0/155
0.00%
0/177
0.31%
1/327 • Number of events 1
Investigations
airway peak pressure increased
0.00%
0/155
0.56%
1/177 • Number of events 1
0.00%
0/327
Investigations
oxygen saturation decreased
0.00%
0/155
0.56%
1/177 • Number of events 1
0.00%
0/327
Renal and urinary disorders
urinary incontinence
0.00%
0/155
0.56%
1/177 • Number of events 1
0.00%
0/327
Respiratory, thoracic and mediastinal disorders
laryngospasm
0.00%
0/155
0.00%
0/177
0.31%
1/327 • Number of events 1
Vascular disorders
flushing
0.00%
0/155
0.56%
1/177 • Number of events 1
0.00%
0/327
Vascular disorders
shock haemorrhagic
1.3%
2/155 • Number of events 3
0.00%
0/177
0.00%
0/327
Vascular disorders
venous thrombosis
0.00%
0/155
0.56%
1/177 • Number of events 1
0.00%
0/327

Other adverse events

Other adverse events
Measure
Spontaneous Reversal
n=155 participants at risk
Participants whose reversal from NMB was spontaneous (no reversal agent used)
Sugammadex
n=177 participants at risk
Participants administered sugammadex for NMB reversal
Other Reversal Agents
n=327 participants at risk
Participants administered any other agent (other than sugammadex) for NMB reversal
Gastrointestinal disorders
nausea
2.6%
4/155 • Number of events 5
5.6%
10/177 • Number of events 10
3.1%
10/327 • Number of events 10
Injury, poisoning and procedural complications
procedural pain
9.7%
15/155 • Number of events 15
7.9%
14/177 • Number of events 14
4.3%
14/327 • Number of events 14
Vascular disorders
hypotension
1.9%
3/155 • Number of events 4
0.56%
1/177 • Number of events 1
5.5%
18/327 • Number of events 20

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Results disclosure agreements

  • Principal investigator is a sponsor employee Results from Investigator's site will initially only be published/presented with results from the other sites, unless permission is obtained to publish separate results. Investigator will not publish interim results. Sponsor must be able to review all proposed study results communications 45 days prior to submission for publication/presentation. If parties disagree concerning appropriateness of proposed content, Investigator will meet with Sponsor's representatives to discuss/resolve any issues.
  • Publication restrictions are in place

Restriction type: OTHER