Efficacy, Safety, and Pharmacokinetics of Sugammadex for Reversal of Neuromuscular Blockade (NMB) in Pediatric Participants (MK-8616-089)
Condition: Neuromuscular Blockade
Intervention: Sugammadex 2 mg/kg; Sugammadex 4 mg/kg; Neostigmine + Glycopyrrolate; Neostigmine + Atropine
Intervention description: For moderate NMB reversal, a single i.v. bolus of sugammadex (2 mg/kg) will be given after final dose of neuromuscular blocking agent (NMBA; rocuronium or vecuronium) and within 2 minutes of the reappearance of a second twitch (T2) in response to TOF stimulations.; For deep NMB reversal, a single i.v. bolus of sugammadex (4 mg/kg) will be given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of detection of a target of 1 to 2 post-tetanic counts and no response to TOF stimulations (TOF=0).; For moderate NMB reversal, a single i.v. bolus containing both neostigmine (50 μg/kg; up to 5 mg maximum dose) as well as glycopyrrolate (10 μg/kg) will be given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of the reappearance of a second twitch (T2) in response to TOF stimulations.; For moderate NMB reversal, a single i.v. bolus containing both neostigmine (50 μg/kg; up to 5 mg maximum dose) as well as atropine (20 μg/kg) will be given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of the reappearance of a second twitch (T2) in response to TOF stimulations.
Intervention MeSH terms: Atropine; Glycopyrrolate; Neostigmine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 288.0
Sex: All
Minimum age: 2 Years
Maximum age: 16 Years
Healthy volunteers: No

Summary:

      This trial will evaluate the efficacy, safety, and pharmacokinetics of sugammadex for the
      reversal of both moderate and deep neuromuscular blockade (NMB) induced by either rocuronium
      or vecuronium in pediatric participants. The primary efficacy hypothesis of this
      investigation is that sugammadex is superior to neostigmine in reversing moderate NMB in
      pediatric participants as measured by time to recovery to a train-of-four (TOF) ratio of
      ≥0.9.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Be categorized as American Society of Anesthesiologists (ASA) Physical Status Class 1,
             2, or 3.

          -  Have a planned non-emergent surgical procedure or clinical situation (e.g.,
             intubation) that requires moderate or deep NMB with either rocuronium or vecuronium.

          -  Have a planned surgical procedure or clinical situation that would allow objective
             neuromuscular monitoring techniques to be applied with access to the arm for
             neuromuscular transmission monitoring.

          -  Age between 2 to <17 years at Visit 2.

          -  If female, may participate if she is not pregnant, not breastfeeding, and at least one
             of the following: 1) Not a woman of childbearing potential (WOCBP); or 2) A WOCBP who
             agrees to follow the study contraceptive guidance during the treatment period and for
             at least 7 days after the last dose of study treatment.

        Exclusion Criteria:

          -  Has any clinically significant condition or situation (eg, anatomical malformation
             that complicates intubation) other than the condition being studied that, in the
             opinion of the investigator, would interfere with the trial evaluations or optimal
             participation in the trial.

          -  Has a neuromuscular disorder that may affect NMB and/or trial assessments.

          -  Is dialysis-dependent or has (or is suspected of having) severe renal insufficiency
             (defined as estimated glomerular filtration rate (eGFR) <30 ml/min).

          -  Has or is suspected of having a family or personal history of malignant hyperthermia.

          -  Has or is suspected of having an allergy 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 and/or fusidic acid via IV
             administration within 24 hours before or within 24 hours after administration of study
             treatment.

          -  Has been previously treated with sugammadex or has participated in a sugammadex
             clinical trial.

          -  Is currently participating in or has participated in an interventional clinical trial
             with an investigational compound or device within 30 days of signing the informed
             consent/assent for this current trial.