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)

NCT00675792 | Completed Phase 3 Results

• 2 other identifiers: P0577419.4.334
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary purpose of this study is to compare the incidence of residual neuromuscular blockade at the time of tracheal extubation after reversal of rocuronium bromide-induced neuromuscular blockade by 4 mg/kg sugammadex with that of 50 µg/kg neostigmine. Residual neuromuscular blockade is defined as the fourth twitch to first twitch (T4/T1) ratio of \< 0.90.

Conditions

Anesthesia

Outcome Measures

Primary Outcomes (1)

• Residual Neuromuscular Blockade Evidenced by T4/T1 Ratio at the Time of Tracheal Extubation

  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.

  Up to the first 24 hours after tracheal extubation

Secondary Outcomes (5)

• Number of Participants With Post-operative Complications

  Up to 7 days after surgery

• Number of Participants With Evidence of Possible Interaction of Sugammadex With Endogenous Compounds or Exogenous Compounds Other Than Rocuronium Bromide

  Up to 7 days after surgery

• Time From Start of Administration of Investigational Medicinal Product (IMP) to Recovery of the T4/T1 Ratio to 0.9

  Up to 1 hour after treatment

• Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.8

  Up to 1 hour after treatment

• Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.7

  Up to 1 hour after treatment

Study Arms (2)

Sugammadex

EXPERIMENTAL

4 mg/kg sugammadex

Drug: Sugammadex; Drug: Rocuronium

Neostigmine

ACTIVE COMPARATOR

50 µg/kg neostigmine

Drug: Neostigmine; Drug: Rocuronium

Interventions

Sugammadex DRUG

Participants received 4 mg/kg sugammadex at 1-2 Post Tetanic Counts (PTCs) or better after the last dose of rocuronium bromide.

Also known as: Org 25969, SCH 900616, MK-8616, Bridion®

Sugammadex

Neostigmine DRUG

Participants received 50 µg/kg neostigmine combined with 10 µg/kg glycopyrrolate after the last dose of rocuronium bromide as per standard of care.

Also known as: Prostigmin®

Neostigmine

Rocuronium DRUG

Participants received a single intubation bolus dose of 0.6 mg/kg rocuronium bromide, followed if necessary to maintain neuromuscular blockade by one or more single bolus dose(s) of 0.15 mg/kg rocuronium bromide.

Also known as: Rocuronium bromide, Esmeron®

Neostigmine; Sugammadex

Eligibility Criteria

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

You may qualify if:

• male or females who are \>= 18 and \<= 65 years of age
• classified by the American Society of Anesthesiologists (ASA) as Class 1 or 2 or 3;
• Body Mass Index (BMI) of \<35 kg/m\^2;
• is scheduled to undergo an elective open abdominal surgical procedure under general anesthesia requiring neuromuscular relaxation using rocuronium bromide (maintenance of neuromuscular blockade if required) for endotracheal intubation and requiring neuromuscular blockade reversal;
• is scheduled to undergo a surgical procedure in a position that does not interfere with the use of TOF-Watch® SX;
• is scheduled to undergo an elective open abdominal procedure expected to last \<=4 hours (from start of skin incision to end of last stitch of the skin);
• have given written informed consent.

You may not qualify if:

• participants for whom a difficult intubation is expected because of anatomical malformations;
• is known or suspected to have neuromuscular disorders that may impair neuromuscular blockade;
• is known or suspected to have significant renal dysfunction (e.g., creatinine clearance \< 30 mL/min) ;
• is known or suspected to have significant hepatic dysfunction;
• is known or suspected to have a (family) history of malignant hyperthermia;
• is known or suspected to have an allergy to opioids, muscle relaxants or other medications used during general anesthesia;
• participants for whom the use of neostigmine and/or glycopyrrolate may be contraindicated;
• participants for whom a pre-established need for postoperative intensive care admission is expected;
• pregnant or breast-feeding females;
• have participated in a previous sugammadex clinical trial;

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Sabo D, Jones RK, Berry J, Sloan T, Chen J-Y, Morte JB, Groudine S. Residual neuromuscular blockade at extubation: a randomized comparison of sugammadex and neostigmine reversal of rocuronium-induced blockade in patients undergoing abdominal surgery. J Anesthe Clin Res. 2011;2:140.

  RESULT

MeSH Terms

Interventions

Sugammadex; Neostigmine; Rocuronium

Intervention Hierarchy (Ancestors)

gamma-Cyclodextrins; Cyclodextrins; Macrocyclic Compounds; Polycyclic Compounds; Dextrins; Starch; Glucans; Polysaccharides; Carbohydrates; Phenylammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Androstanols; Androstanes; Steroids; Fused-Ring Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2008
• First Posted: May 12, 2008
• Study Start: May 1, 2008
• Primary Completion: September 1, 2008
• Study Completion: September 1, 2008
• Last Updated: March 13, 2015
• Results First Posted: July 11, 2013

Record last verified: 2015-02