Clinical trial NCT03346057: Safety of Sugammadex for the Reversal of Neuromuscular Blockade in American Society of Anesthesiologists (ASA) Class 3 or 4 Participants (MK-8616-145)
Official title: A Phase 4 Randomized, Active-Comparator Controlled Clinical Trial to Study the Safety of Sugammadex (MK-8616) for the Reversal of Neuromuscular Blockade Induced by Either Rocuronium Bromide or Vecuronium Bromide in American Society of Anesthesiologists (ASA) Class 3 or 4 Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Reversal of Neuromuscular Blockade
Keywords: arrhythmia, bradycardia, neuromuscular blocking agents, surgery, tachycardia
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2017-11-17
Enrollment: 344
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percentage of Participants With Treatment-Emergent Sinus Bradycardia Events
timeFrame: Up to approximately 35 minutes post-administration
measure: Percentage of Participants With Treatment-Emergent Sinus Tachycardia Events
timeFrame: Up to approximately 35 minutes post-administration
measure: Percentage of Participants With Other Treatment-Emergent Cardiac Arrhythmia Events
timeFrame: Up to approximately 35 minutes post-administration
measure: Percentage of Participants Experiencing an Adverse Event (AE) Up To 7 Days After Administration of Study Intervention
timeFrame: Up to 7 days
measure: Percentage of Participants Experiencing a Serious Adverse Event (SAE) Up To 7 Days After Administration of Study Intervention
timeFrame: Up to 7 days
measure: Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention
timeFrame: Up to 7 days
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama - Birmingham ( Site 1046)
state: Alabama
city: Tucson
country: United States
facility: University Banner Medical Center ( Site 1019)
state: Arizona
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center ( Site 1029)
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center ( Site 1001)
state: California
city: Miami
country: United States
facility: Jackson Memorial Hospital ( Site 1007)
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Medical Center ( Site 1050)
state: Kansas
city: New Orleans
country: United States
facility: Tulane University ( Site 1057)
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation ( Site 1005)
state: Louisiana
city: Boston
country: United States
facility: Brigham & Women's Hospital ( Site 1039)
state: Massachusetts
city: Royal Oak
country: United States
facility: Beaumont Hospital, Royal Oak ( Site 1034)
state: Michigan
city: Columbia
country: United States
facility: University Hospital- Columbia MO ( Site 1060)
state: Missouri
city: Columbia
country: United States
facility: University of Missouri Health Care ( Site 1022)
state: Missouri
city: Neptune
country: United States
facility: Jersey Shore University Medical Center ( Site 1058)
state: New Jersey
city: New Brunswick
country: United States
facility: Saint Peter's University Hospital [New Brunswick, NJ] ( Site 1017)
state: New Jersey
city: Asheville
country: United States
facility: Mission Hospital - Memorial ( Site 1016)
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clin Foundation ( Site 1032)
state: Ohio
city: Philadelphia
country: United States
facility: Temple University Hospital ( Site 1004)
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center ( Site 1033)
state: Tennessee
city: Houston
country: United States
facility: Hermann Drive Surgical Center ( Site 1021)
state: Texas
city: Milwaukee
country: United States
facility: Zablocki VA Medical Center ( Site 1011)
state: Wisconsin
city: Dornbirn
country: Austria
facility: A.O. Krankenhaus Dornbirn ( Site 1151)
state: Voralberg
city: Feldkirch
country: Austria
facility: Landeskrankenhaus Feldkirch ( Site 1152)
city: Wien
country: Austria
facility: Sozialmedizinisches Zentrum Ost - Donauspital ( Site 1150)
city: Aarhus
country: Denmark
facility: Aarhus Universitets hospital ( Site 1252)
city: Copenhagen NV
country: Denmark
facility: Bispebjerg og Frederiksberg Hospital ( Site 1250)
city: Copenhagen
country: Denmark
facility: Rigshospitalet ( Site 1253)
city: Viborg
country: Denmark
facility: Regionshospitalet Viborg ( Site 1254)
city: Muenchen
country: Germany
facility: Klinikum Rechts der Isar Technische Universitaet Muenchen ( Site 1350)
city: Reutlingen
country: Germany
facility: Klinikum am Steinenberg Reutlingen ( Site 1352)
city: Warendorf
country: Germany
facility: Josephs-Hospitals Warendorf ( Site 1351)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.