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

NCT ID: NCT03346057

Last Updated: 2020-10-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 344 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-20
• Study Completion Date: 2019-09-04

Brief 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.

Conditions

Reversal of Neuromuscular Blockade

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Sugammadex 2 mg/kg

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

Group Type: EXPERIMENTAL

Sugammadex 2 mg/kg

Intervention Type: DRUG

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.

Rocuronium

Intervention Type: DRUG

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.

Vecuronium

Intervention Type: DRUG

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.

Sugammadex 4 mg/kg

Sugammadex 4 mg/kg administered as a single IV dose

Group Type: EXPERIMENTAL

Sugammadex 4 mg/kg

Intervention Type: DRUG

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.

Rocuronium

Intervention Type: DRUG

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.

Vecuronium

Intervention Type: DRUG

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.

Sugammadex 16 mg/kg

Sugammadex 16 mg/kg administered as a single IV dose

Group Type: EXPERIMENTAL

Sugammadex 16 mg/kg

Intervention Type: DRUG

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.

Rocuronium

Intervention Type: DRUG

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.

Neostigmine + Glycopyrrolate

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

Group Type: ACTIVE_COMPARATOR

Neostigmine + Glycopyrrolate

Intervention Type: DRUG

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.

Rocuronium

Intervention Type: DRUG

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.

Vecuronium

Intervention Type: DRUG

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.

Interventions

Sugammadex 2 mg/kg

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.

Intervention Type: DRUG

Sugammadex 4 mg/kg

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.

Intervention Type: DRUG

Sugammadex 16 mg/kg

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.

Intervention Type: DRUG

Neostigmine + Glycopyrrolate

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.

Intervention Type: DRUG

Rocuronium

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.

Intervention Type: DRUG

Vecuronium

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 Type: DRUG

Other Intervention Names

MK-8616; Bridion; MK-8616; Bridion; MK-8616; Bridion

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

University of Alabama - Birmingham ( Site 1046)

Birmingham, Alabama, United States

University Banner Medical Center ( Site 1019)

Tucson, Arizona, United States

Loma Linda University Medical Center ( Site 1029)

Loma Linda, California, United States

University of California Davis Medical Center ( Site 1001)

Sacramento, California, United States

Jackson Memorial Hospital ( Site 1007)

Miami, Florida, United States

University of Kansas Medical Center ( Site 1050)

Kansas City, Kansas, United States

Tulane University ( Site 1057)

New Orleans, Louisiana, United States

Ochsner Clinic Foundation ( Site 1005)

New Orleans, Louisiana, United States

Brigham & Women's Hospital ( Site 1039)

Boston, Massachusetts, United States

Beaumont Hospital, Royal Oak ( Site 1034)

Royal Oak, Michigan, United States

University Hospital- Columbia MO ( Site 1060)

Columbia, Missouri, United States

University of Missouri Health Care ( Site 1022)

Columbia, Missouri, United States

Jersey Shore University Medical Center ( Site 1058)

Neptune City, New Jersey, United States

Saint Peter's University Hospital [New Brunswick, NJ] ( Site 1017)

New Brunswick, New Jersey, United States

Mission Hospital - Memorial ( Site 1016)

Asheville, North Carolina, United States

Cleveland Clin Foundation ( Site 1032)

Cleveland, Ohio, United States

Temple University Hospital ( Site 1004)

Philadelphia, Pennsylvania, United States

Vanderbilt University Medical Center ( Site 1033)

Nashville, Tennessee, United States

Hermann Drive Surgical Center ( Site 1021)

Houston, Texas, United States

Zablocki VA Medical Center ( Site 1011)

Milwaukee, Wisconsin, United States

A.O. Krankenhaus Dornbirn ( Site 1151)

Dornbirn, Voralberg, Austria

Landeskrankenhaus Feldkirch ( Site 1152)

Feldkirch, , Austria

Sozialmedizinisches Zentrum Ost - Donauspital ( Site 1150)

Vienna, , Austria

Aarhus Universitets hospital ( Site 1252)

Aarhus, , Denmark

Rigshospitalet ( Site 1253)

Copenhagen, , Denmark

Bispebjerg og Frederiksberg Hospital ( Site 1250)

Copenhagen NV, , Denmark

Regionshospitalet Viborg ( Site 1254)

Viborg, , Denmark

Klinikum Rechts der Isar Technische Universitaet Muenchen ( Site 1350)

München, , Germany

Klinikum am Steinenberg Reutlingen ( Site 1352)

Reutlingen, , Germany

Josephs-Hospitals Warendorf ( Site 1351)

Warendorf, , Germany

Countries

United States; Austria; Denmark; Germany

References

Herring WJ, Mukai Y, Wang A, Lutkiewicz J, Lombard JF, Lin L, Watkins M, Broussard DM, Blobner M. A randomized trial evaluating the safety profile of sugammadex in high surgical risk ASA physical class 3 or 4 participants. BMC Anesthesiol. 2021 Oct 28;21(1):259. doi: 10.1186/s12871-021-01477-5.

Reference Type: DERIVED

PMID: 34711192 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2017-000187-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MK-8616-145

Identifier Type: OTHER

Identifier Source: secondary_id

8616-145

Identifier Type: -

Identifier Source: org_study_id