Trial Outcomes & Findings for Comparison of Sugammadex Administered at 1-2 Post Tetanic Counts (PTCs) or Better With Neostigmine Administered as Per Standard of Care to Reverse Rocuronium-Induced Neuromuscular Blockade in Adults Undergoing Elective Open Abdominal Procedure (19.4.334) (P05774) (NCT NCT00675792)

Last Updated: 2015-03-13

Results Overview

Neuromuscular function was monitored by applying repetitive Train-Of-Four (TOF) electrical stimulations to the ulnar nerve every 15 seconds, and assessing twitch response at the adductor pollicis muscle with a TOF-Watch® SX. The magnitudes (heights) of the first and fourth twitches (T1 and T4) were used to calculate the T4/T1 ratio, where a higher T4/T1 ratio indicates a greater recovery from neuromuscular blockade, with a value of 1.0 indicating complete recovery. After anesthesia, when neuromuscular function was expected to be fully recovered, tracheal extubation was performed, at which time the T4/T1 ratio was measured, with any missing recovery times imputed.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

100 participants

Primary outcome timeframe

Up to the first 24 hours after tracheal extubation

Results posted on

2015-03-13

Participant Flow

Participant milestones

Participant milestones
Measure	Sugammadex 4 mg/kg sugammadex	Neostigmine 50 µg/kg neostigmine
Overall Study STARTED	51	49
Overall Study COMPLETED	51	49
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Comparison of Sugammadex Administered at 1-2 Post Tetanic Counts (PTCs) or Better With Neostigmine Administered as Per Standard of Care to Reverse Rocuronium-Induced Neuromuscular Blockade in Adults Undergoing Elective Open Abdominal Procedure (19.4.334) (P05774)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sugammadex n=51 Participants 4 mg/kg sugammadex	Neostigmine n=49 Participants 50 µg/kg neostigmine	Total n=100 Participants Total of all reporting groups
Age, Continuous	49 years STANDARD_DEVIATION 11 • n=5 Participants	52 years STANDARD_DEVIATION 9 • n=7 Participants	51 years STANDARD_DEVIATION 10 • n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants	31 Participants n=7 Participants	60 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	18 Participants n=7 Participants	40 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to the first 24 hours after tracheal extubation

Population: Intent to treat (ITT) group consisting of all randomized participants who were treated with sugammadex or neostigmine and had at least one efficacy measurement. Three participants treated with neostigmine did not have at least one efficacy measurement, and hence were excluded from the analysis.

Outcome measures

Outcome measures
Measure	Sugammadex n=51 Participants 4 mg/kg sugammadex	Neostigmine n=46 Participants 50 µg/kg neostigmine
Residual Neuromuscular Blockade Evidenced by T4/T1 Ratio at the Time of Tracheal Extubation	1.02 T4/T1 Ratio Standard Deviation 0.15	0.78 T4/T1 Ratio Standard Deviation 0.24

SECONDARY outcome

Timeframe: Up to 7 days after surgery

Population: All subjects treated (AST) group consisting of randomized participants who were treated with sugammadex or neostigmine

Post-operative complications include any of the following: procedural pain, nausea, vomiting, incision-site pain, constipation, headache, pyrexia, dizziness and pruritus.

Outcome measures

Outcome measures
Measure	Sugammadex n=51 Participants 4 mg/kg sugammadex	Neostigmine n=49 Participants 50 µg/kg neostigmine
Number of Participants With Post-operative Complications	51 participants	49 participants

SECONDARY outcome

Timeframe: Up to 7 days after surgery

Population: All subjects treated (AST) group consisting of randomized participants who were treated with sugammadex or neostigmine

Evidence of adverse events due to a possible interaction of sugammadex with exogenous compounds or endogenous compounds other than rocuronium was recorded.

Outcome measures

Outcome measures
Measure	Sugammadex n=51 Participants 4 mg/kg sugammadex	Neostigmine n=49 Participants 50 µg/kg neostigmine
Number of Participants With Evidence of Possible Interaction of Sugammadex With Endogenous Compounds or Exogenous Compounds Other Than Rocuronium Bromide	0 participants	0 participants

SECONDARY outcome

Timeframe: Up to 1 hour after treatment

Population: ITT group consisting of all randomized participants who were treated with sugammadex or neostigmine and had at least one efficacy measurement. Three participants treated with neostigmine did not have at least one efficacy measurement, and hence were excluded from the analysis.

Neuromuscular function was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds, and assessing T1 and T4 twitch response at the adductor pollicis muscle with a TOF-Watch® SX. Nerve stimulation was continued until the T4/T1 ratio, which indicates the extent of recovery from neuromuscular blockade, achieved a ratio of 0.9, with imputed data included.

Outcome measures

Outcome measures
Measure	Sugammadex n=51 Participants 4 mg/kg sugammadex	Neostigmine n=46 Participants 50 µg/kg neostigmine
Time From Start of Administration of Investigational Medicinal Product (IMP) to Recovery of the T4/T1 Ratio to 0.9	2.53 Minutes Standard Deviation 1.18	7.95 Minutes Standard Deviation 6.92

SECONDARY outcome

Timeframe: Up to 1 hour after treatment

Outcome measures

Outcome measures
Measure	Sugammadex n=51 Participants 4 mg/kg sugammadex	Neostigmine n=46 Participants 50 µg/kg neostigmine
Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.8	1.87 Minutes Standard Deviation 0.82	6.18 Minutes Standard Deviation 5.73

SECONDARY outcome

Timeframe: Up to 1 hour after treatment

Outcome measures

Outcome measures
Measure	Sugammadex n=51 Participants 4 mg/kg sugammadex	Neostigmine n=46 Participants 50 µg/kg neostigmine
Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.7	1.60 Minutes Standard Deviation 0.72	4.98 Minutes Standard Deviation 4.98

Adverse Events

Sugammadex

Serious events: 4 serious events

Other events: 51 other events

Deaths: 0 deaths

Neostigmine

Serious events: 6 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sugammadex n=51 participants at risk 4 mg/kg sugammadex	Neostigmine n=49 participants at risk 50 µg/kg neostigmine
Cardiac disorders Atrial fibrillation	2.0% 1/51 • Number of events 1 • Up to 7 days after administration of IMP	0.00% 0/49 • Up to 7 days after administration of IMP
Gastrointestinal disorders Constipation	0.00% 0/51 • Up to 7 days after administration of IMP	2.0% 1/49 • Number of events 1 • Up to 7 days after administration of IMP
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/51 • Up to 7 days after administration of IMP	4.1% 2/49 • Number of events 2 • Up to 7 days after administration of IMP
Infections and infestations Pelvic abscess	0.00% 0/51 • Up to 7 days after administration of IMP	2.0% 1/49 • Number of events 1 • Up to 7 days after administration of IMP
Infections and infestations Wound infection staphylococcal	0.00% 0/51 • Up to 7 days after administration of IMP	2.0% 1/49 • Number of events 1 • Up to 7 days after administration of IMP
Injury, poisoning and procedural complications Anastomotic leak	2.0% 1/51 • Number of events 1 • Up to 7 days after administration of IMP	0.00% 0/49 • Up to 7 days after administration of IMP
Injury, poisoning and procedural complications Postoperative ileus	2.0% 1/51 • Number of events 1 • Up to 7 days after administration of IMP	0.00% 0/49 • Up to 7 days after administration of IMP
Injury, poisoning and procedural complications Postoperative wound complication	2.0% 1/51 • Number of events 1 • Up to 7 days after administration of IMP	0.00% 0/49 • Up to 7 days after administration of IMP
Metabolism and nutrition disorders Fluid overload	0.00% 0/51 • Up to 7 days after administration of IMP	2.0% 1/49 • Number of events 1 • Up to 7 days after administration of IMP
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/51 • Up to 7 days after administration of IMP	2.0% 1/49 • Number of events 1 • Up to 7 days after administration of IMP
Respiratory, thoracic and mediastinal disorders Bronchial secretion retention	0.00% 0/51 • Up to 7 days after administration of IMP	2.0% 1/49 • Number of events 1 • Up to 7 days after administration of IMP
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/51 • Up to 7 days after administration of IMP	2.0% 1/49 • Number of events 1 • Up to 7 days after administration of IMP

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee In case a proposed publication contains reference to an invention owned by the sponsor or to which the sponsor otherwise has rights, the sponsor may request a reasonable suspension of the publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Sugammadex n=51 participants at risk 4 mg/kg sugammadex	Neostigmine n=49 participants at risk 50 µg/kg neostigmine
Gastrointestinal disorders Abdominal distension	9.8% 5/51 • Number of events 5 • Up to 7 days after administration of IMP	2.0% 1/49 • Number of events 1 • Up to 7 days after administration of IMP
Gastrointestinal disorders Constipation	11.8% 6/51 • Number of events 6 • Up to 7 days after administration of IMP	12.2% 6/49 • Number of events 6 • Up to 7 days after administration of IMP
Gastrointestinal disorders Flatulence	7.8% 4/51 • Number of events 4 • Up to 7 days after administration of IMP	6.1% 3/49 • Number of events 3 • Up to 7 days after administration of IMP
Gastrointestinal disorders Ileus	0.00% 0/51 • Up to 7 days after administration of IMP	6.1% 3/49 • Number of events 3 • Up to 7 days after administration of IMP
Gastrointestinal disorders Nausea	51.0% 26/51 • Number of events 26 • Up to 7 days after administration of IMP	49.0% 24/49 • Number of events 24 • Up to 7 days after administration of IMP
Gastrointestinal disorders Vomiting	17.6% 9/51 • Number of events 9 • Up to 7 days after administration of IMP	22.4% 11/49 • Number of events 11 • Up to 7 days after administration of IMP
General disorders Pyrexia	13.7% 7/51 • Number of events 7 • Up to 7 days after administration of IMP	4.1% 2/49 • Number of events 2 • Up to 7 days after administration of IMP
Injury, poisoning and procedural complications Incision site pain	13.7% 7/51 • Number of events 7 • Up to 7 days after administration of IMP	18.4% 9/49 • Number of events 9 • Up to 7 days after administration of IMP
Injury, poisoning and procedural complications Procedural hypertension	2.0% 1/51 • Number of events 1 • Up to 7 days after administration of IMP	6.1% 3/49 • Number of events 4 • Up to 7 days after administration of IMP
Injury, poisoning and procedural complications Procedural nausea	2.0% 1/51 • Number of events 1 • Up to 7 days after administration of IMP	8.2% 4/49 • Number of events 4 • Up to 7 days after administration of IMP
Injury, poisoning and procedural complications Procedural pain	80.4% 41/51 • Number of events 41 • Up to 7 days after administration of IMP	77.6% 38/49 • Number of events 38 • Up to 7 days after administration of IMP
Nervous system disorders Dizziness	11.8% 6/51 • Number of events 6 • Up to 7 days after administration of IMP	4.1% 2/49 • Number of events 2 • Up to 7 days after administration of IMP
Nervous system disorders Headache	5.9% 3/51 • Number of events 3 • Up to 7 days after administration of IMP	14.3% 7/49 • Number of events 7 • Up to 7 days after administration of IMP
Psychiatric disorders Insomnia	5.9% 3/51 • Number of events 3 • Up to 7 days after administration of IMP	2.0% 1/49 • Number of events 1 • Up to 7 days after administration of IMP
Renal and urinary disorders Bladder spasm	7.8% 4/51 • Number of events 4 • Up to 7 days after administration of IMP	8.2% 4/49 • Number of events 4 • Up to 7 days after administration of IMP
Respiratory, thoracic and mediastinal disorders Hiccups	5.9% 3/51 • Number of events 3 • Up to 7 days after administration of IMP	0.00% 0/49 • Up to 7 days after administration of IMP
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/51 • Up to 7 days after administration of IMP	6.1% 3/49 • Number of events 3 • Up to 7 days after administration of IMP
Skin and subcutaneous tissue disorders Pruritus	5.9% 3/51 • Number of events 3 • Up to 7 days after administration of IMP	10.2% 5/49 • Number of events 5 • Up to 7 days after administration of IMP