Clinical trial NCT00535743: Dose-Finding Trial With Sugammadex Administered at 3 and 15 Minutes After 1.0 and 1.2 mg/kg Rocuronium Bromide in Participants of ASA Class 1-3 (P05944; MK-8616-024)
Official title: A Multi-Center, Randomized, Safety Assessor-Blinded, Placebo- Controlled, Phase II, Parallel Dose-Finding Trial in Subjects of ASA 1-3 to Assess the Efficacy and Safety of 5 Doses of Sugammadex Administered at 3 and 15 Minutes After Administration of 1.0 and 1.2 mg/kg Rocuronium Bromide
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anesthesia, General
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2007-09-26
Enrollment: 174
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this trial was to explore the dose-response relation of sugammadex (Org 25969; MK-8616) administered for the reversal of neuromuscular blockade (NMB) at 3 and 15 minutes following administration of 1.0 and 1.2 mg/kg of Esmeron® (rocuronium) in participants receiving surgery, classified as American Society of Anesthesiologists (ASA) class 1 (otherwise normal, healthy participant), class 2 (participant with mild systemic disease), or class 3 (participant with a severe systemic disease that limits activity, but is not incapacitating).

Detailed description: In the United States, the highest dose recommended in the package insert of Zemuron® (i.e. the trade name for Esmeron® in the US) is 1.2 mg/kg whereas in Europe it is 1.0 mg/kg. For both doses, dose recommendations for reversal with sugammadex were to be found. Hence, the present trial was set up to explore the dose-response relation of sugammadex given as an NMB reversal agent at 3 and 15 minutes following administration of 1.0 and 1.2 mg/kg of Esmeron® in subjects of ASA 1 to 3. The sub-investigator who performed any subjective safety assessments after anesthesia was to be remained blinded.

Eligibility criteria: Inclusion Criteria:

* Participants of ASA class 1 - 3, above or equal to the age of 18 years;
* Participants scheduled for surgical procedures with an anticipated duration of anesthesia of at least 120 minutes, without further need for muscle relaxation other than for intubation;
* Participants scheduled for surgical procedures in supine position;
* Participants who had given written informed consent.

Exclusion Criteria:

* Participants in whom a difficult intubation because of anatomical malformations was expected;
* Participants known or suspected to have neuromuscular disorders impairing neuromuscular blocking and/or significant renal dysfunction;
* Participants known or suspected to have a (family) history of malignant hyperthermia;
* Participants known or suspected to have an allergy to narcotics, muscle relaxants or other medication used during general anesthesia;
* Participants receiving medication known to interfere with neuromuscular blocking agents, such as anticonvulsants and Mg\^2+;
* Participants who had already participated in this trial;
* Participants who had participated in another clinical trial, not pre-approved by the Sponsor, within 30 days of entering into this trial;
* Female participants who were pregnant: in females, pregnancy was to be excluded both from medical history and by a human chorionic gonadotropin (hCG) test within 24 hours before surgery except in females who were not of childbearing potential, i.e. at least 2 years menopausal or who had undergone tubal ligation or an hysterectomy;
* Female participants of childbearing potential not using any of the following methods of birth control (for one month): condom or diaphragm with spermicide, vasectomized partner (\>6 months), intrauterine device (IUD), abstinence;
* Female participants who were breast-feeding.

Primary outcomes:
measure: Mean Time From Start of Study Treatment Administration to Recovery of the T4/T1 Ratio to 0.9
timeFrame: Up to 240 minutes following administration of study treatment
Secondary outcomes:
measure: Mean Time From Start of Study Treatment Administration to Recovery of the T4/T1 Ratio to 0.8
timeFrame: Up to 200 minutes following administration of study treatment
measure: Mean Time From Start of Study Treatment Administration to Recovery of the T4/T1 Ratio to 0.7
timeFrame: Up to 180 minutes following administration of study treatment
measure: Number of Participants Experiencing an Adverse Event
timeFrame: Up to 7 days following administration of study treatment
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Puhringer FK, Rex C, Sielenkamper AW, Claudius C, Larsen PB, Prins ME, Eikermann M, Khuenl-Brady KS. Reversal of profound, high-dose rocuronium-induced neuromuscular blockade by sugammadex at two different time points: an international, multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial. Anesthesiology. 2008 Aug;109(2):188-97. doi: 10.1097/ALN.0b013e31817f5bc7.