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

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ClinicalTrials.gov Identifier: NCT03346057
Recruitment Status : Recruiting
First Posted : November 17, 2017
Last Update Posted : May 16, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
This is a randomized, active comparator-controlled, parallel-group, multi-site, double-blind safety trial of sugammadex (MK-8616) for the reversal of neuromuscular blockade (NMB) induced by rocuronium or vecuronium in adult ASA Physical Status Class 3 and 4 participants. The first primary objective of this study is to characterize the incidence of treatment emergent sinus bradycardia, treatment emergent sinus tachycardia, or other treatment emergent cardiac arrhythmias after administration of sugammadex. The second primary objective of this study is to evaluate the general safety of sugammadex in a population of ASA Class 3 and 4 subjects in a surgical setting.

Condition or disease Intervention/treatment Phase
Reversal of Neuromuscular Blockade Drug: Sugammadex 2 mg/kg Drug: Sugammadex 4 mg/kg Drug: Sugammadex 16 mg/kg Drug: Neostigmine + Glycopyrrolate Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 331 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : December 20, 2017
Estimated Primary Completion Date : December 26, 2019
Estimated Study Completion Date : December 26, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Sugammadex 2 mg/kg
Sugammadex 2 mg/kg administered as a single intravenous (IV) dose
Drug: Sugammadex 2 mg/kg
Sugammadex 2 mg/kg, administered as a single bolus injection into a fast-running IV line on the day of surgery, for moderate block and reversal in participants receiving the NMBA rocuronium or vecuronium. Moderate block is a level of NMB in which peripheral nerve stimulation elicits one to four muscle twitches.
Other Name: MK-8616

Experimental: Sugammadex 4 mg/kg
Sugammadex 4 mg/kg administered as a single IV dose
Drug: Sugammadex 4 mg/kg
Sugammadex 4 mg/kg, administered as a single bolus injection into a fast-running IV line on the day of surgery, for deep block and reversal in participants receiving the NMBA rocuronium or vecuronium. 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.
Other Name: MK-8616

Experimental: Sugammadex 16 mg/kg
Sugammadex 16 mg/kg administered as a single IV dose
Drug: Sugammadex 16 mg/kg
Sugammadex 16 mg/kg, administered as a single bolus injection into a fast-running IV line on the day of surgery, for deep block and reversal in participants receiving the NMBA rocuronium
Other Name: MK-8616

Active Comparator: 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
Drug: Neostigmine + Glycopyrrolate
Neostigmine 50 μg/kg plus glycopyrrolate 10 μg/kg, administered as a single bolus injection into a fast-running IV line on the day of surgery, for moderate block and reversal in participants receiving the NMBA rocuronium or vecuronium




Primary Outcome Measures :
  1. Percentage of Participants Experiencing Treatment Emergent Sinus Bradycardia After Administration of Sugammadex [ Time Frame: 30 minutes post-administration ]
    Sinus bradycardia is defined as a heart rate <60 bpm which has also decreased more than 20% compared to the participant's baseline heart rate value, and has been sustained for at least 1 minute after administration of study treatment.

  2. Percentage of Participants Experiencing Treatment Emergent Sinus Tachycardia After Administration of Sugammadex [ Time Frame: 30 minutes post-administration ]
    Sinus tachycardia is defined as a heart rate >=100 bpm which has also decreased more than 20% compared to the participant's baseline heart rate value, and has been sustained for at least 1 minute after administration of study treatment.

  3. Percentage of Participants Experiencing Treatment Emergent Cardiac Arrhythmias After Administration of Sugammadex [ Time Frame: 30 minutes post-administration ]
    The percentage of participants experiencing treatment emergent cardiac arrhythmias necessitating intervention (e. g., new or worsening atrial fibrillation, atrial tachycardia, ventricular tachycardia, or ventricular fibrillation) The arrhythmia has been sustained for at least 1 minute after administration of study treatment.

  4. Percentage of Participants Experiencing One or More Adverse Events After Treatment with Sugammadex [ Time Frame: Up to 7 days ]
  5. Percentage of Participants Experiencing Hypersensitivity or Anaphylaxis [ Time Frame: Up to 7 days ]
  6. Percentage of Participants Experiencing Sinus Bradycardia or Sinus Tachycardia Necessitating Intervention [ Time Frame: Up to 7 days ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03346057


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

  Show 29 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.

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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03346057     History of Changes
Other Study ID Numbers: 8616-145
2017-000187-15 ( EudraCT Number )
First Posted: November 17, 2017    Key Record Dates
Last Update Posted: May 16, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck Sharp & Dohme Corp.:
arrhythmia, bradycardia, neuromuscular blocking agents, surgery, tachycardia

Additional relevant MeSH terms:
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Rocuronium
Vecuronium Bromide
Neostigmine
Glycopyrrolate
Neuromuscular Nondepolarizing Agents
Neuromuscular Blocking Agents
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Parasympathomimetics
Autonomic Agents
Adjuvants, Anesthesia
Muscarinic Antagonists
Cholinergic Antagonists
Nicotinic Antagonists