A Bridging Trial Comparing Sugammadex (Org 25969) at Reappearance of T2 in Japanese and Caucasian Participants. Part B: Caucasian Participants (P05971)

NCT ID: NCT00552617

Last Updated: 2019-11-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-20
• Study Completion Date: 2006-08-31

Brief Summary

The objective of the trial was to establish the dose-response relation of sugammadex (Org 25969) given as a reversal agent of rocuronium or vecuronium at reappearance of T2 (the amplitude of the first response of second twitch to train of four (TOF) stimulation, expressed as percentage of control first twitch, T1) during sevoflurane anesthesia for Caucasian participants.

Detailed Description

For most surgical procedures a depth of neuromuscular block of 1-2 twitches after TOF-stimulation is sufficient to avoid unwanted muscular activity. At reappearance of T2, the anesthesiologist might decide to either give (another) maintenance dose of rocuronium or vecuronium when surgery continues, to await spontaneous recovery of neuromuscular block or to reverse the neuromuscular block. Sugammadex has been shown in previous trials to greatly reduce the time to full recovery when administered at reappearance of T2, both after rocuronium- and vecuronium induced neuromuscular blockade. The current trial P05971 was conducted in Europe and set up to establish the dose response relationship of sugammadex given during sevoflurane anesthesia at reappearance of T2 after rocuronium or vecuronium in Caucasian participants. In addition to recovery time, also pharmacokinetics and safety of sugammadex were to be evaluated.

Conditions

Anesthesia, General

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Rocuronium + Placebo

After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered intravenously (IV), followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of placebo was administered IV.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

After induction of anesthesia an intubation dose of NMBA was administered IV: either 0.9 mg/kg rocuronium (arm 1) or 0.1 mg/kg vecuronium (arm 6).

Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.

At reappearance of T2 the randomized single dose of Placebo IV was administered

Rocuronium

Intervention Type: DRUG

After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV.

Maintenance doses of 0.1-0.2 mg/kg rocuronium IV could be administered if necessary.

Rocuronium + 0.5 mg/kg Sugammadex

After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 0.5 mg/kg sugammadex was administered IV.

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: DRUG

After induction of anesthesia an intubation dose of (Neuromuscular blocking agent) NMBA was administered IV: either 0.9 mg/kg rocuronium or 0.1 mg/kg vecuronium.

Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.

At reappearance of T2 the randomized single dose of sugammadex 0.5 to 4 mg/kg IV was administered

Rocuronium

Intervention Type: DRUG

After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV.

Maintenance doses of 0.1-0.2 mg/kg rocuronium IV could be administered if necessary.

Rocuronium + 1.0 mg/kg Sugammadex

After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 1.0 mg/kg sugammadex was administered IV.

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: DRUG

After induction of anesthesia an intubation dose of (Neuromuscular blocking agent) NMBA was administered IV: either 0.9 mg/kg rocuronium or 0.1 mg/kg vecuronium.

Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.

At reappearance of T2 the randomized single dose of sugammadex 0.5 to 4 mg/kg IV was administered

Rocuronium

Intervention Type: DRUG

After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV.

Maintenance doses of 0.1-0.2 mg/kg rocuronium IV could be administered if necessary.

Rocuronium + 2.0 mg/kg Sugammadex

After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 2.0 mg/kg sugammadex was administered IV.

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: DRUG

After induction of anesthesia an intubation dose of (Neuromuscular blocking agent) NMBA was administered IV: either 0.9 mg/kg rocuronium or 0.1 mg/kg vecuronium.

Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.

At reappearance of T2 the randomized single dose of sugammadex 0.5 to 4 mg/kg IV was administered

Rocuronium

Intervention Type: DRUG

After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV.

Maintenance doses of 0.1-0.2 mg/kg rocuronium IV could be administered if necessary.

Rocuronium + 4.0 mg/kg Sugammadex

After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 4.0 mg/kg sugammadex was administered IV.

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: DRUG

After induction of anesthesia an intubation dose of (Neuromuscular blocking agent) NMBA was administered IV: either 0.9 mg/kg rocuronium or 0.1 mg/kg vecuronium.

Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.

At reappearance of T2 the randomized single dose of sugammadex 0.5 to 4 mg/kg IV was administered

Rocuronium

Intervention Type: DRUG

After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV.

Maintenance doses of 0.1-0.2 mg/kg rocuronium IV could be administered if necessary.

Vecuronium + Placebo

After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of placebo was administered IV.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

After induction of anesthesia an intubation dose of NMBA was administered IV: either 0.9 mg/kg rocuronium (arm 1) or 0.1 mg/kg vecuronium (arm 6).

Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.

At reappearance of T2 the randomized single dose of Placebo IV was administered

Vecuronium

Intervention Type: DRUG

After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV. Maintenance doses of 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.

Vecuronium + 0.5 mg/kg Sugammadex

After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 0.5 mg/kg sugammadex was administered IV.

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: DRUG

After induction of anesthesia an intubation dose of (Neuromuscular blocking agent) NMBA was administered IV: either 0.9 mg/kg rocuronium or 0.1 mg/kg vecuronium.

Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.

At reappearance of T2 the randomized single dose of sugammadex 0.5 to 4 mg/kg IV was administered

Vecuronium

Intervention Type: DRUG

After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV. Maintenance doses of 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.

Vecuronium + 1.0 mg/kg Sugammadex

After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 1.0 mg/kg sugammadex was administered IV.

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: DRUG

After induction of anesthesia an intubation dose of (Neuromuscular blocking agent) NMBA was administered IV: either 0.9 mg/kg rocuronium or 0.1 mg/kg vecuronium.

Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.

At reappearance of T2 the randomized single dose of sugammadex 0.5 to 4 mg/kg IV was administered

Vecuronium

Intervention Type: DRUG

After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV. Maintenance doses of 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.

Vecuronium + 2.0 mg/kg Sugammadex

After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 2.0 mg/kg sugammadex was administered IV.

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: DRUG

After induction of anesthesia an intubation dose of (Neuromuscular blocking agent) NMBA was administered IV: either 0.9 mg/kg rocuronium or 0.1 mg/kg vecuronium.

Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.

At reappearance of T2 the randomized single dose of sugammadex 0.5 to 4 mg/kg IV was administered

Vecuronium

Intervention Type: DRUG

After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV. Maintenance doses of 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.

Vecuronium + 4.0 mg/kg Sugammadex

After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 4.0 mg/kg sugammadex was administered IV.

Group Type: EXPERIMENTAL

Sugammadex

Intervention Type: DRUG

After induction of anesthesia an intubation dose of (Neuromuscular blocking agent) NMBA was administered IV: either 0.9 mg/kg rocuronium or 0.1 mg/kg vecuronium.

Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.

At reappearance of T2 the randomized single dose of sugammadex 0.5 to 4 mg/kg IV was administered

Vecuronium

Intervention Type: DRUG

After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV. Maintenance doses of 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.

Interventions

Sugammadex

After induction of anesthesia an intubation dose of (Neuromuscular blocking agent) NMBA was administered IV: either 0.9 mg/kg rocuronium or 0.1 mg/kg vecuronium.

Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.

At reappearance of T2 the randomized single dose of sugammadex 0.5 to 4 mg/kg IV was administered

Intervention Type: DRUG

Placebo

After induction of anesthesia an intubation dose of NMBA was administered IV: either 0.9 mg/kg rocuronium (arm 1) or 0.1 mg/kg vecuronium (arm 6).

Maintenance doses of 0.1-0.2 mg/kg rocuronium IV or 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.

At reappearance of T2 the randomized single dose of Placebo IV was administered

Intervention Type: DRUG

Rocuronium

After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV.

Maintenance doses of 0.1-0.2 mg/kg rocuronium IV could be administered if necessary.

Intervention Type: DRUG

Vecuronium

After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV. Maintenance doses of 0.02-0.03 mg/kg vecuronium IV could be administered if necessary.

Intervention Type: DRUG

Other Intervention Names

Org 25969

Eligibility Criteria

Inclusion Criteria

• Is of American Society of Anesthesiologists (ASA) class 1 - 3;
• Is at least 20 years but under 65 years of age;
• Caucasian participants;
• Is scheduled for elective surgery requiring muscle relaxation in supine position and under sevoflurane anesthesia with an anticipated duration of about 1.5-3 hours;
• Has given written informed consent.

Exclusion Criteria

• Participants in whom a difficult intubation because of anatomical malformations was expected;
• Is known or suspected to have neuromuscular disorders impairing neuromuscular blocking (NMB) and/or significant renal dysfunction (for example a creatinine level > 1.6 mg/dl) and/or severe hepatic dysfunction.
• Is known or suspected to have a (family) history of malignant hyperthermia;
• Is known or suspected to have an allergy to narcotics, muscle relaxants or other medication used during general anesthesia;
• Is receiving medication expected to interfere with the rocuronium or vecuronium given in this trial, based on the dose and time of administration;
• Females who were pregnant;
• Females of childbearing potential not using birth control or using only oral contraception as birth control;
• Was breast-feeding;
• Has already participated in P05971, or in another trial with sugammadex;
• Has participated in another clinical trial, not preapproved by the Sponsor, within 6 months of entering into P05971.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Puhringer FK, Gordon M, Demeyer I, Sparr HJ, Ingimarsson J, Klarin B, van Duijnhoven W, Heeringa M. Sugammadex rapidly reverses moderate rocuronium- or vecuronium-induced neuromuscular block during sevoflurane anaesthesia: a dose-response relationship. Br J Anaesth. 2010 Nov;105(5):610-9. doi: 10.1093/bja/aeq226. Epub 2010 Sep 28.

Reference Type: RESULT

PMID: 20876699 (View on PubMed)

Study Documents

Document Type: CSr Synopsis

View Document

Related Links

http://www.merck.com/clinical-trials/policies-perspectives.html

Click here to access a synopsis of the study results.

Other Identifiers

19.4.208B

Identifier Type: OTHER

Identifier Source: secondary_id

MK-8616-035

Identifier Type: OTHER

Identifier Source: secondary_id

2005-001133-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

P05971

Identifier Type: -

Identifier Source: org_study_id