DANCHEONG: Comparison of Sugammadex With Neostigmine as Reversal Agents for Rocuronium at Reappearance of T2 (Study P06101)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01050543
• Collaborator: (none)
• Enrollment: 128
• Arms: 2
• Actual Duration (Months): 6.6

Study Details

Study Description

Brief Summary

This is a randomized, active-controlled, parallel-group, single-dose, multi-site, safety-assessor blinded study comparing sugammadex to neostigmine for reversal of neuromuscular blockade in Korean subjects undergoing elective surgical procedures under general anesthesia that require rocuronium for neuromuscular blockade. Study medication will be administered at reappearance of T2. Time to recovery will be measured from start of study medication administration to recovery of the T4/T1 ratio of 0.9. The primary hypothesis is that the time to recovery of the T4/T1 ratio of 0.9 is shorter with sugammadex than with neostigmine.

Condition or Disease	Intervention/Treatment	Phase
Neuromuscular Blockade	Drug: sugammadex; Drug: neostigmine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 128 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Safety-Assessor Blinded Trial Comparing Sugammadex With Neostigmine in Korean Subjects Scheduled for Surgeries Requiring Moderate Neuromuscular Blockade
• Actual Study Start Date: Feb 1, 2010
• Actual Primary Completion Date: Aug 20, 2010
• Actual Study Completion Date: Aug 20, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sugammadex	Drug: sugammadex; sugammadex 2.0 mg/kg, single intravenous bolus dose administered within 10 seconds into a fast flowing venous infusion; Other Names: SCH 900616; Bridion
Active Comparator: Neostigmine	Drug: neostigmine; neostigmine 50 mcg/kg (total dose not to exceed 5.0 mg) combined with glycopyrrolate 10 mcg/kg, single intravenous bolus dose administered within 10 seconds into a fast flowing venous infusion; Other Names: neostigmine methylsulfate

Outcome Measures

Primary Outcome Measures

1. Time From Start of Study Drug Administration to Recovery of the T4/T1 Ratio to 0.9 [From Start of Study Drug Administration to Recovery of the T4/T1 Ratio to 0.9 (estimated from 2 minutes up to ~15 minutes)]

   Neuromuscular functioning was monitored by applying repetitive Train-Of-Four (TOF) electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 & T4 refer to the magnitudes (height) of the 1st & 4th twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0) indicates the extent of recovery from neuromuscular blockade. In this study, twitch responses were recorded until the T4/T1 Ratio reached >= 0.9, the minimum acceptable ratio that indicated complete recovery.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• American Society of Anesthesiologists Class 1 or 2 or 3

• =18 years of age and of either sex

• scheduled for elective surgical procedure under general anesthesia requiring the use of rocuronium for endotracheal intubation and/or maintenance of neuromuscular blockade in a supine position allowing neuromuscular transmission monitoring and requiring reversal of neuromuscular blockade

• Korean descent born in Korea, never emigrated out of Korea, and have a Korean home address

Exclusion Criteria:

• expected difficult intubation due to anatomic malformations

• expected transfer to intensive care unit after surgery

• neuromuscular disorders affecting neuromuscular blockade

• significant hepatic or renal dysfunction

• require use of pneumatic tourniquet during surgery

• (family) history of malignant hyperthermia

• allergy to cyclodextrins (including sugammadex) or other medication(s) used during general anesthesia; use of toremifene or fusidic acid within 24 hours of study drug administration; contraindication to use of neostigmine or glycopyrrolate

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT01050543
• Other Study ID Numbers: P06101
• First Posted: Jan 15, 2010
• Last Update Posted: Jul 2, 2017
• Last Verified: Jun 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Neostigmine

Study Results

Participant Flow

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	sugammadex 2 mg/kg	neostigmine 50 mcg/kg
Period Title: Overall Study
STARTED	64	64
COMPLETED	60	60
NOT COMPLETED	4	4

Baseline Characteristics

Arm/Group Title	Sugammadex	Neostigmine	Total
Arm/Group Description	sugammadex 2 mg/kg	neostigmine 50 mcg/kg	Total of all reporting groups
Overall Participants	60	60	120
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.3 (14.0)	42.6 (14.0)	42.0 (13.9)
Sex: Female, Male (Count of Participants)
Female	21 35%	23 38.3%	44 36.7%
Male	39 65%	37 61.7%	76 63.3%

Outcome Measures

1. Primary Outcome

Title	Time From Start of Study Drug Administration to Recovery of the T4/T1 Ratio to 0.9
Description	Neuromuscular functioning was monitored by applying repetitive Train-Of-Four (TOF) electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 & T4 refer to the magnitudes (height) of the 1st & 4th twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0) indicates the extent of recovery from neuromuscular blockade. In this study, twitch responses were recorded until the T4/T1 Ratio reached >= 0.9, the minimum acceptable ratio that indicated complete recovery.
Time Frame	From Start of Study Drug Administration to Recovery of the T4/T1 Ratio to 0.9 (estimated from 2 minutes up to ~15 minutes)

Outcome Measure Data

Analysis Population Description

Full Analysis Set, defined as all participants who received randomized treatment and had at least one efficacy measurement.

Arm/Group Title	Sugammadex	Neostigmine
Arm/Group Description	sugammadex 2 mg/kg	neostigmine 50 mcg/kg
Measure Participants	59	59
Geometric Mean (95% Confidence Interval) [minutes]	1.77	14.80

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sugammadex, Neostigmine
	Comments	To evaluate the efficacy of sugammadex compared to the efficacy of neostigmine, the ratio of the geometric means of time to recovery of the T4/T1 ratio to 0.9 was calculated using a 2-way ANOVA model adjusted for trial site.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	8.1
	Confidence Interval	(2-Sided) 95%; 6.8 to 9.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Sugammadex		Neostigmine
Arm/Group Description	sugammadex 2 mg/kg		neostigmine 50 mcg/kg
All Cause Mortality
	Sugammadex		Neostigmine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sugammadex		Neostigmine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/60 (3.3%)		2/60 (3.3%)
Infections and infestations
Post-operative abscess	1/60 (1.7%)	1	0/60 (0%)	0
Injury, poisoning and procedural complications
Intestinal anastomosis complication	1/60 (1.7%)	1	0/60 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to bone	0/60 (0%)	0	1/60 (1.7%)	1
Renal and urinary disorders
Dysuria	0/60 (0%)	0	1/60 (1.7%)	1
Other (Not Including Serious) Adverse Events
	Sugammadex		Neostigmine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/60 (60%)		42/60 (70%)
Gastrointestinal disorders
Nausea	4/60 (6.7%)	4	4/60 (6.7%)	4
Injury, poisoning and procedural complications
Incision site pain	7/60 (11.7%)	9	12/60 (20%)	16
Procedural hypotension	4/60 (6.7%)	6	1/60 (1.7%)	2
Procedural pain	20/60 (33.3%)	22	18/60 (30%)	19
Wound complication	3/60 (5%)	3	6/60 (10%)	6
Nervous system disorders
Headache	7/60 (11.7%)	8	9/60 (15%)	10

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The sponsor shall have the right to review and comment with respect to publications with regard to the following concerns: proprietary information; accuracy of the information; and to ensure that the presentation is fairly balanced and in compliance with FDA regulations. The investigator further agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the trial.