Efficacy and Safety of Sugammadex Dosed According to Actual Body Weight (ABW) or Ideal Body Weight (IBW) in Reversal of Neuromuscular Blockade (NMB) in Morbidly Obese Participants (MK-8616-146)
Condition: Neuromuscular Blockade
MeSH terms: Body Weight
Intervention: Sugammadex 2 mg/kg ABW; Sugammadex 2 mg/kg IBW; Sugammadex 4 mg/kg ABW; Sugammadex 4 mg/kg IBW; Neostigmine + Glycopyrrolate; Rocuronium or 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 by ABW) for reversal of moderate NMB.
Moderate NMB is defined as the reappearance of a second twitch (T2) in response to TOF stimulations.; Following administration of NMBA (Rocuronium or Vecuronium) to achieve moderate NMB, participants received a single i.v. bolus of Sugammadex (2 mg/kg by IBW) for reversal of moderate NMB.
Moderate NMB is defined as the reappearance of T2 in response to TOF stimulations.; Following administration of NMBA (Rocuronium or Vecuronium) to achieve deep NMB, participants received a single i.v. bolus of Sugammadex (4 mg/kg by ABW) for reversal of deep NMB.
Deep NMB is defined as no response to TOF stimulations (TOF=0) and a detection target of 1-2 post-tetanic counts (PTCs).; Following administration of NMBA (Rocuronium or Vecuronium) to achieve deep NMB, participants will receive a single i.v. bolus of Sugammadex (4 mg/kg by IBW) for reversal of deep NMB.
Deep NMB is defined as no response to TOF stimulations (TOF=0) and a detection target of 1-2 post-tetanic counts (PTCs).; 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), dosed according to participant ABW for reversal of moderate NMB.
Moderate NMB is defined as the reappearance of T2 in response to TOF stimulations.; To achieve NMB, participants received steroidal NMBA Rocuronium Bromide or Vecuronium Bromide administered via i.v. infusion and dosed according to participant ABW. NMBAs were concomitant medications used per label as 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: 207.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this trial is to evaluate the safety and efficacy of Sugammadex when
      administered according to actual body weight (ABW) as compared to ideal body weight (IBW) for
      the reversal of both moderate and deep neuromuscular blockade (NMB) induced by either
      Rocuronium or Vecuronium in morbidly obese participants. The primary hypothesis of this
      investigation is that, compared to obese participants dosed based on IBW, obese participants
      receiving Sugammadex according to ABW will demonstrate a faster time to recovery to a Train
      Of Four (TOF) ratio of ≥0.9 (i.e. faster NMB reversal), pooled across NMB depth and type of
      neuromuscular blocking agent (NMBA; Rocuronium or Vecuronium) administered.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have BMI ≥40 kg/m² (morbidly obese).

          -  Be categorized as American Society of Anesthesiologists (ASA) Physical Status Class 3

          -  Have a planned surgical procedure that requires neuromuscular block with either
             rocuronium or vecuronium.

          -  Have a planned surgical procedure (e.g., gastrointestinal, urologic, or laparoscopic
             procedures) that in the opinion of the investigator does not preclude maintenance of
             moderate or deep depth of NMB throughout the case (maintained by re-dosing or
             continuous infusion).

          -  Have a planned surgical procedure that would allow objective neuromuscular monitoring
             techniques to be applied with access to the arm for neuromuscular transmission
             monitoring.

          -  If female, who is not of reproductive potential, be one of the following: 1)
             postmenopausal (defined as at least 12 months with no menses in women ≥45 years of
             age; 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 as the planned surgical procedure associated with participation
             in this study (e.g., hysterectomy or tubal ligation).

          -  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. Please note the following: 1) Medically accepted
             methods of contraception include condoms (male or female) with a spermicidal agent,
             diaphragm or cervical cap with spermicide, medically prescribed intrauterine device
             (IUD), inert or copper-containing IUD, surgical sterilization (e.g., hysterectomy or
             tubal ligation); 2) 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
             Human Subjects Protection Review Boards; 3 Periodic abstinence (e.g., calendar,
             ovulation, sympto-thermal, post-ovulation methods, etc.) and withdrawal are not
             acceptable methods of contraception; 4) If a contraceptive method listed above is
             restricted by local regulations/guidelines, then it does not qualify as an acceptable
             method of contraception for subjects participating at sites in this country/region.

          -  Be able to provide (or the subject'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:

          -  Have an actual body weight <100 kg.

          -  Have a pacemaker or automatic implantable cardioverter-defibrillator that precludes
             the assessment of bradycardia or arrhythmias.

          -  Have a medical condition or surgical procedure that precludes reversal of
             neuromuscular block at the end of surgery.

          -  Have neuromuscular disorder(s) that may affect neuromuscular block and/or trial
             assessments.

          -  Are dialysis-dependent or have severe renal insufficiency (defined as estimated
             creatinine clearance of <30 mL/min.).

          -  Have or are suspected of having a personal history or family history (parents,
             grandparents, or siblings) of malignant hyperthermia.

          -  Have or are 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.

          -  Have received or are planning to receive toremifene within 24 hours before or within
             24 hours after study medication administration.

          -  Have any condition that would contraindicate the administration of study medication.

          -  Are currently pregnant, attempting to become pregnant, or lactating.

          -  Have any clinically significant condition or situation (e.g., 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.

          -  Are currently participating in or has participated in an interventional clinical trial
             with an investigational compound (including any other current or ongoing trial with a
             Sugammadex treatment arm) or device within 30 days of signing the informed consent
             form of this current trial.