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)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 4

Conditions: Neuromuscular Blockade

Treatments: Drug: Neostigmine + Glycopyrrolate; Drug: Rocuronium or Vecuronium; Drug: Sugammadex 2 mg/kg IBW; Drug: Sugammadex 2 mg/kg ABW; Drug: Sugammadex 4 mg/kg ABW; Drug: Sugammadex 4 mg/kg IBW

Study type: Interventional

Funder types: Industry

Identifiers

NCT03346070

MK-8616-146 (Other Identifier)

8616-146

2017-000188-33 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 207 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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207 participants in 5 patient groups

Sugammadex 2 mg/kg ABW

Experimental group

Description:

Following administration of NMBA, participants received a single intravenous (i.v.) bolus of Sugammadex at 2 mg/kg as determined utilizing participant ABW. A treatment dose of 2 mg/kg was used for reversal of moderate NMB.

Treatment:

Drug: Sugammadex 2 mg/kg ABW

Drug: Rocuronium or Vecuronium

Sugammadex 2 mg/kg IBW

Experimental group

Description:

Following administration of NMBA, participants received a single i.v. bolus of Sugammadex at 2 mg/kg as determined utilizing participant IBW. A treatment dose of 2 mg/kg was used for reversal of moderate NMB.

Treatment:

Drug: Sugammadex 2 mg/kg IBW

Drug: Rocuronium or Vecuronium

Sugammadex 4 mg/kg ABW

Experimental group

Description:

Following administration of NMBA, participants received a single i.v. bolus of Sugammadex at 4 mg/kg as determined utilizing participant ABW. A treatment dose of 4 mg/kg was used for reversal of deep NMB.

Treatment:

Drug: Sugammadex 4 mg/kg ABW

Drug: Rocuronium or Vecuronium

Sugammadex 4 mg/kg IBW

Experimental group

Description:

Following administration of NMBA, participants received a single i.v. bolus of Sugammadex at 4 mg/kg as determined utilizing participant IBW. A treatment dose of 4 mg/kg was used for reversal of deep NMB.

Treatment:

Drug: Sugammadex 4 mg/kg IBW

Drug: Rocuronium or Vecuronium

Neostigmine/Glycopyrrolate

Active Comparator group

Description:

Following administration of NMBA, participants received a single i.v. bolus containing both Neostigmine (50 µg/kg; up to 5 mg maximum dose) and Glycopyrrolate (10 µg/kg; up to 1 mg maximum dose) as determined utilizing participant ABW. Neostigmine/Glycopyrrolate was used for reversal of moderate NMB. Active comparator treatment for reversal for deep NMB was not available.

Treatment:

Drug: Neostigmine + Glycopyrrolate

Drug: Rocuronium or Vecuronium