Safety of Sugammadex for the Reversal of Neuromuscular Blockade in American Society of Anesthesiologists (ASA) Class 3 or 4 Participants (MK-8616-145)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 4

Conditions: Reversal of Neuromuscular Blockade

Treatments: Drug: Vecuronium; Drug: Neostigmine + Glycopyrrolate; Drug: Sugammadex 4 mg/kg; Drug: Rocuronium; Drug: Sugammadex 16 mg/kg; Drug: Sugammadex 2 mg/kg

Study type: Interventional

Funder types: Industry

Identifiers

NCT03346057

2017-000187-15 (EudraCT Number)

MK-8616-145 (Other Identifier)

8616-145

Details and patient eligibility

About

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.

Enrollment: 344 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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344 participants in 4 patient groups

Sugammadex 2 mg/kg

Experimental group

Description:

Sugammadex 2 mg/kg administered as a single intravenous (IV) dose

Treatment:

Drug: Sugammadex 2 mg/kg

Drug: Vecuronium

Drug: Rocuronium

Sugammadex 4 mg/kg

Experimental group

Description:

Sugammadex 4 mg/kg administered as a single IV dose

Treatment:

Drug: Vecuronium

Drug: Sugammadex 4 mg/kg

Drug: Rocuronium

Sugammadex 16 mg/kg

Experimental group

Description:

Sugammadex 16 mg/kg administered as a single IV dose

Treatment:

Drug: Sugammadex 16 mg/kg

Drug: Rocuronium

Neostigmine + Glycopyrrolate

Active Comparator group

Description:

Neostigmine 50 μg/kg (up to 5 mg maximum dose) plus glycopyrrolate 10 μg/kg (up to 1 mg maximum dose) administered as a single IV dose

Treatment:

Drug: Vecuronium

Drug: Neostigmine + Glycopyrrolate

Drug: Rocuronium