Clinical trial NCT00552617: A Bridging Trial Comparing Sugammadex (Org 25969) at Reappearance of T2 in Japanese and Caucasian Participants. Part B: Caucasian Participants (P05971)
Official title: A Multi-Center, Randomized, Open-Label, Prospective Bridging, Parallel Dose-Finding Trial Comparing Efficacy, Safety and Pharmacokinetics of 4 Doses of Org 25969 and Placebo Administered at Reappearance of T2 After Rocuronium or Vecuronium in Japanese and Caucasian Subjects. Part B: Caucasian Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anesthesia, General
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2007-11-02
Enrollment: 100
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Time From Start of Administration of Sugammadex or Placebo to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9
timeFrame: Day 1: From start of sugammadex or placebo administration to recovery of T4/T1 ratio to 0.9 (up to 24 hours)
Secondary outcomes:
measure: Time From Start of Administration of Sugammadex or Placebo to Recovery of the T4/T1 Ratio to 0.7
timeFrame: Day 1: From start of sugammadex or placebo administration to recovery of T4/T1 ratio to 0.7 (up to 24 hours)
measure: Time From Start of Administration of Sugammadex or Placebo to Recovery of the T4/T1 Ratio to 0.8
timeFrame: Day 1: From start of sugammadex or placebo administration to recovery of T4/T1 ratio to 0.8 (up to 24 hours)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.