Safety of Sugammadex for the Reversal of Neuromuscular Blockade in American Society of Anesthesiologists (ASA) Class 3 or 4 Participants (MK-8616-145)
Condition: Reversal of Neuromuscular Blockade
Intervention: Sugammadex 2 mg/kg; Sugammadex 4 mg/kg; Sugammadex 16 mg/kg; Neostigmine + Glycopyrrolate; Rocuronium; Vecuronium
Intervention description: Following administration of NMBA (Rocuronium or Vecuronium) to achieve moderate NMB, participants received a single i.v. bolus of Sugammadex 2 mg/kg for reversal of moderate NMB. Moderate block is a level of NMB in which peripheral nerve stimulation elicits one to four muscle twitches.; Following administration of NMBA (Rocuronium or Vecuronium) to achieve deep NMB, participants received a single i.v. bolus of Sugammadex 4 mg/kg for reversal of deep NMB. Deep block is a level of NMB in which peripheral nerve stimulation elicits no muscle twitches and high-frequency muscle stimulation elicits minimal levels of muscle contraction.; Following administration of NMBA (Rocuronium) to achieve deep NMB, participants received a single i.v. bolus of Sugammadex 16 mg/kg for reversal of deep NMB. Deep block is a level of NMB in which peripheral nerve stimulation elicits no muscle twitches and high-frequency muscle stimulation elicits minimal levels of muscle contraction.; Following administration of NMBA (Rocuronium or Vecuronium) to achieve moderate NMB, participants received a single i.v. bolus of Neostigmine (50 μg/kg; 5 mg maximum) and Glycopyrrolate (10 μg/kg; 1 mg maximum) for reversal of moderate NMB. Moderate block is a level of NMB in which peripheral nerve stimulation elicits one to four muscle twitches.; To achieve NMB, participants received steroidal NMBA Rocuronium Bromide administered via IV infusion and dosed according to participant body weight. NMBAs were concomitant medications used per label and at Investigator's discretion as an adjunct to general anesthesia.; To achieve NMB, participants received steroidal NMBA Vecuronium Bromide administered via IV infusion and dosed according to participant body weight. NMBAs were concomitant medications used per label and at Investigator's discretion as an adjunct to general anesthesia.
Intervention MeSH terms: Glycopyrrolate; Rocuronium; Vecuronium Bromide; Neostigmine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 344.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: arrhythmia, bradycardia, neuromuscular blocking agents, surgery, tachycardia

Summary:

      The purpose of this trial is to evaluate the safety of sugammadex for the reversal of
      neuromuscular blockade (NMB) induced by neuromuscular blockade agents (NMBA) rocuronium or
      vecuronium in adult American Society of Anesthesiologists (ASA) Physical Status Class 3 and 4
      participants. The primary objectives of the study are to characterize the incidence of
      treatment emergent sinus bradycardia, treatment emergent sinus tachycardia, or other
      treatment emergent cardiac arrhythmias after administration of sugammadex and to evaluate the
      general safety of sugammadex in a population of ASA Class 3 and 4 participants in a surgical
      setting.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has a body mass index (BMI) < 40 kg/m2.

          -  Is categorized as ASA Physical Status Class 3 or 4, as determined by the Investigator.

          -  Has a planned surgical procedure that requires NMB with either rocuronium or
             vecuronium.

          -  Has a planned surgical procedure (e.g., gastrointestinal, urologic, or laparoscopic)
             that in the opinion of the investigator does not preclude maintenance of moderate or
             deep depth of NMB throughout the case.

          -  If female who is not of reproductive potential, is one of the following: (1)
             postmenopausal; (2) has had a hysterectomy and/or bilateral oophorectomy, bilateral
             salpingectomy, or bilateral tubal ligation/occlusion at least 6 weeks prior to
             screening; (3) has a congenital or acquired condition that prevents childbearing; or
             (4) is undergoing surgical sterilization (e.g., hysterectomy or tubal ligation) as the
             planned surgical procedure associated with participation in this study.

          -  If female who is sexually active and of child-bearing potential, agrees to use a
             medically accepted method of contraception through seven days after receiving
             protocol-specified medication. Abstinence (relative to heterosexual activity) can be
             used as the sole method of contraception if it is consistently employed as the
             subject's preferred and usual lifestyle and if considered acceptable by local
             regulatory agencies and Ethics Review Committees/Institutional Review Boards.

          -  Is able to provide (or the participant's legally authorized representative, in
             accordance with local requirements), written informed consent for the trial. The
             participant or legally authorized representative may also provide consent for Future
             Biomedical Research.

        Exclusion Criteria:

          -  Has a pacemaker or automatic implantable cardioverter-defibrillator that precludes the
             assessment of bradycardia or arrhythmias.

          -  Has a medical condition or surgical procedure that precludes reversal of neuromuscular
             block at the end of surgery.

          -  Has a neuromuscular disorder(s) that may affect neuromuscular block and/or trial
             assessments.

          -  Is dialysis-dependent or has severe renal insufficiency, defined as estimated
             creatinine clearance of <30 mL/min.

          -  Has or is suspected of having a personal history or family history (parents,
             grandparents, or siblings) of malignant hyperthermia.

          -  Has or is suspected of having an allergy (e.g., hypersensitivity and/or anaphylactic
             reaction) to study treatments or its/their excipients, to opioids/opiates, muscle
             relaxants or their excipients, or other medication(s) used during general anesthesia.

          -  Has received or is planned to receive toremifene within 24 hours before or within 24
             hours after study medication administration.

          -  Has any condition that would contraindicate the administration of study medication.

          -  Is pregnant, is attempting to become pregnant, or is lactating.

          -  Is currently participating in or has participated in an interventional clinical trial
             (including any other current or ongoing trial with a sugammadex treatment arm) with an
             investigational compound or device within 30 days of signing the informed consent form
             of this current trial.