A Multicenter, Randomized, Parallel Group, Comparative, Safety-Assessor Blinded, Phase IIIa Trial in Adult Surgical Subjects Under General Anesthesia at Increased Risk for Pulmonary Complications
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 86
- Primary Endpoint
- Time From Start of Sugammadex Administration to Recovery of T4/T1 Ratio to 0.9 in Participants With or Having a Past History of Pulmonary Disease
Study Overview
Brief Summary
The purpose of the trial is to research the safety and to show faster recovery after administration of 2.0 mg/kg or 4.0 mg/kg sugammadex (Org 25969, MK-8616) given as a reversal agent for 0.6 mg/kg (0.15 mg/kg maintenance dose) rocuronium (Zemuron®) in participants diagnosed with or having a history of pulmonary disease. All drug administration will be via the intravenous (IV) route.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •American Society of Anesthesiologists (ASA) Class 1 to 3;
- •Has been diagnosed with or having a past history of pulmonary disease;
- •Is scheduled for elective surgical procedure under general anesthesia requiring neuromuscular block with the use of rocuronium;
- •Is scheduled for surgery in supine position;
- •Has given written informed consent;
Exclusion Criteria
- •Is expected to have a difficult intubation due to anatomical malformations;
- •Has known or suspected of having neuromuscular disorders impairing neuromuscular blockade and/or significant renal dysfunction;
- •Has known or suspected of having a (family) history of malignant hyperthermia;
- •Has known or suspected of having an allergy to narcotics, muscle relaxants or other medications used during surgery;
- •Is receiving medication known to interfere with neuromuscular blocking agents such as anticonvulsants, antibiotics and Mg2+;
- •Is a female who is pregnant or breast-feeding;
- •Is a female of childbearing potential not using an acceptable method of birth control [condom or diaphragm with spermicide, vasectomized partner (> 6 months), IUD, abstinence] or using only hormonal contraception as birth control;
- •Has already participated in a sugammadex trial including Protocol 19.4.308;
- •Has participated in another clinical trial, not pre-approved by Organon, within 30 days of entering into Protocol 19.4.308.
Arms & Interventions
Rocuronium + Sugammadex 2.0 mg/kg
After the IV intubation dose (0.6 mg/kg) or last maintenance dose (0.15 mg/kg) of rocuronium, at reappearance of T2, participants will receive IV sugammadex 2.0 mg/kg.
Intervention: Sugammadex (Drug)
Rocuronium + Sugammadex 2.0 mg/kg
After the IV intubation dose (0.6 mg/kg) or last maintenance dose (0.15 mg/kg) of rocuronium, at reappearance of T2, participants will receive IV sugammadex 2.0 mg/kg.
Intervention: Rocuronium (Drug)
Rocuronium + Sugammadex 4.0 mg/kg
After the IV intubation dose (0.6 mg/kg) or last maintenance dose (0.15 mg/kg) of rocuronium, at reappearance of T2, participants will receive IV sugammadex 4.0 mg/kg.
Intervention: Sugammadex (Drug)
Rocuronium + Sugammadex 4.0 mg/kg
After the IV intubation dose (0.6 mg/kg) or last maintenance dose (0.15 mg/kg) of rocuronium, at reappearance of T2, participants will receive IV sugammadex 4.0 mg/kg.
Intervention: Rocuronium (Drug)
Outcomes
Primary Outcomes
Time From Start of Sugammadex Administration to Recovery of T4/T1 Ratio to 0.9 in Participants With or Having a Past History of Pulmonary Disease
Time Frame: Up to 90 minutes
The mean time from the start of sugammadex administration to recovery of the T4/T1 ratio to 0.9 was determined. Less time indicates faster recovery from neuromuscular blockade. The ratio of T4 (fourth twitch; amplitude of fourth response to train of four \[TOF\] stimulation is expressed as percent of control T4) over T1 (first twitch; amplitude of first response to TOF stimulation is expressed as percent of control T1) ranges from 0 (complete loss of T4 twitch response) to 1.0 (complete recovery of T4 twitch response). For TOF stimulation, 4 consecutive square wave supra-maximal stimuli of 0.2 msec duration were delivered at 2 Hz every 15 seconds. Neuromuscular monitoring was performed with the TOF-Watch® SX.
Percentage of Participants Experiencing ≥1 Adverse Event(s) (AE)
Time Frame: Up to 7 days
The percentage of participants experiencing ≥1 AE(s) was determined for each arm. An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Percentage of Participants Discontinuing Study Treatment Due to an Adverse Event (AE)
Time Frame: Up to 7 days
The percentage of participants discontinuing from study treatment due to an AE was determined for each arm. An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Secondary Outcomes
- Five-Second Head Lift Assessment 1: Prior to Transfer to the Recovery Room Following Extubation(Up to 6 hours (prior to transfer to the recovery room after extubation))
- Time From Start of Sugammadex Administration to Recovery of T4/T1 Ratio to 0.7 in Participants With or Having a Past History of Pulmonary Disease(Up to 90 minutes)
- Time From Start of Sugammadex Administration to Recovery of T4/T1 Ratio to 0.8 in Participants With or Having a Past History of Pulmonary Disease(Up to 90 minutes)
- Level of Consciousness Assessment 2: Prior to Discharge From the Recovery Room(Up to 6 hours (prior to discharge from the recovery room))
- Level of Consciousness Assessment 1: Prior to Transfer to the Recovery Room Following Extubation(Up to 6 hours (prior to transfer to the recovery room after extubation))
- General Muscle Weakness Assessment 2: Prior to Discharge From the Recovery Room(Up to 6 hours (prior to discharge from the recovery room))
- Five-Second Head Lift Assessment 2: Prior to Discharge From the Recovery Room(Up to 6 hours (prior to discharge from the recovery room))
- General Muscle Weakness Assessment 1: Prior to Transfer to the Recovery Room Following Extubation(Up to 6 hours (prior to transfer to the recovery room after extubation))