Back to results

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)

Primary Purpose

Neuromuscular Blockade

Status

Completed

Phase

Phase 4

Locations

International

Study Type

Interventional

Intervention

Sugammadex 2 mg/kg ABW

Sugammadex 2 mg/kg IBW

Sugammadex 4 mg/kg ABW

Sugammadex 4 mg/kg IBW

Neostigmine + Glycopyrrolate

Rocuronium or Vecuronium

About this trial

This is an interventional treatment trial for Neuromuscular Blockade

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

University California / Davis ( Site 2001)
Jackson Memorial Hospital/University of Miami ( Site 2007)
University of Kansas Medical Center ( Site 2049)
William Beaumont Hospital - Royal Oak ( Site 2033)
University Hospital- Columbia MO ( Site 2060)
Robert Wood Johnson University Hospital ( Site 2037)
Mission Hospital - St. Joseph ( Site 2015)
Cleveland Clinic Foundation ( Site 2031)
Temple University Hospital ( Site 2004)
Vanderbilt University Medical Center ( Site 2032)
Hermann Drive Surgical Center ( Site 2020)
Hermann Drive Surgical Center ( Site 2059)
Zablocki VA Medical Center ( Site 2011)
Sozialmedizinisches Zentrum Ost - Donauspital ( Site 2150)
Universitaire Ziekenhuis Antwerpen - UZA ( Site 2200)
Bispebjerg og Frederiksberg Hospital ( Site 2250)
Rigshospitalet ( Site 2253)
Johanniter Krankenhaus Bonn ( Site 2353)
Diakovere Annastift gGmbH ( Site 2355)
Universitatsklinikum Giessen und Marburg GmbH ( Site 2356)
Klinikum Rechts der Isar Technische Universitaet Muenchen ( Site 2350)
St. Franziskus-Hospital ( Site 2354)
Klinikum am Steinenberg Reutlingen ( Site 2352)
Josephs-Hospitals Warendorf ( Site 2351)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Active Comparator

Arm Label

Sugammadex 2 mg/kg ABW

Sugammadex 2 mg/kg IBW

Sugammadex 4 mg/kg ABW

Sugammadex 4 mg/kg IBW

Neostigmine/Glycopyrrolate

Arm 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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Time to Recovery (TTR) of Participant Train Of Four (TOF) Ratio to ≥0.9: Primary Kaplan-Meier Analysis

The primary efficacy analysis of TTR of TOF ratio to ≥0.9 was performed by estimating event rates within each treatment group using the Kaplan-Meier method. TTR was monitored by applying electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to magnitudes of the first and fourth twitches respectively, after nerve stimulation. The T4/T1 ratio (TOF; expressed as a decimal of up to 1.0) indicates the extent of recovery from NMB. A faster TTR of the TOF ratio to 0.9 indicates faster recovery from NMB. As specified by the protocol, analyses for this outcome measure were conducted in participants pooled by dosing method across depth of NMB (Sugammadex ABW [2 mg/kg ABW plus 4 mg/kg ABW] and Sugammadex IBW [2 mg/kg IBW plus 4 mg/kg IBW]) as well as in all randomized treatment arms separated by depth of NMB (Sugammadex 2 mg/kg ABW, Sugammadex 4 mg/kg ABW, Sugammadex 2 mg/kg IBW, and Sugammadex 4 mg/kg IBW).

Percentage of Participants With Treatment-Emergent Sinus Bradycardia Events

The percentage of participants experiencing treatment-emergent bradycardia events were identified with continuous electrocardiogram (ECG) monitoring. Treatment-emergent sinus bradycardia is defined as a heart rate <60 bpm that has also decreased more than 20% compared to participant baseline heart rate value, sustained for at least 1 minute after administration of study intervention. Treatment-emergent sinus bradycardia events may or may not be considered an adverse event (AE), as determined by investigator judgment. As specified by the protocol, analyses for this outcome measure were conducted in participants pooled by dosing method across depth of NMB (Sugammadex ABW [2 mg/kg ABW plus 4 mg/kg ABW] and Sugammadex IBW [2 mg/kg IBW plus 4 mg/kg IBW]) as well as in all randomized treatment arms separated by depth of NMB (Sugammadex 2 mg/kg ABW, Sugammadex 4 mg/kg ABW, Sugammadex 2 mg/kg IBW, and Sugammadex 4 mg/kg IBW).

Percentage of Participants With Treatment-Emergent Sinus Tachycardia Events

The percentage of participants experiencing treatment-emergent sinus tachycardia events were identified with continuous ECG monitoring. Treatment-emergent sinus tachycardia is defined as a heart rate ≥100 bpm that has also increased more than 20% compared to participant baseline heart rate value, sustained for at least 1 minute after administration of study intervention. Treatment-emergent sinus tachycardia events may or may not be considered an AE, as determined by investigator judgment. As specified by the protocol, analyses for this outcome measure were conducted in participants pooled by dosing method across depth of NMB (Sugammadex ABW [2 mg/kg ABW plus 4 mg/kg ABW] and Sugammadex IBW [2 mg/kg IBW plus 4 mg/kg IBW]) as well as in all randomized treatment arms separated by depth of NMB (Sugammadex 2 mg/kg ABW, Sugammadex 4 mg/kg ABW, Sugammadex 2 mg/kg IBW, and Sugammadex 4 mg/kg IBW).

Percentage of Participants With Other Treatment-Emergent Cardiac Arrhythmia Events

The percentage of participants experiencing other treatment-emergent cardiac arrhythmia events were identified with continuous ECG monitoring. Other treatment-emergent cardiac arrhythmias are defined as new or worsening arrhythmias (e.g., atrial fibrillation, atrial tachyarrhythmia, ventricular fibrillation, or ventricular tachyarrhythmia), sustained for at least 1 minute after administration of study intervention. Worsening arrhythmia events may or may not be considered an AE, as determined by investigator judgment. As specified by the protocol, analyses for this outcome measure were conducted in participants pooled by dosing method across depth of NMB (Sugammadex ABW [2 mg/kg ABW plus 4 mg/kg ABW] and Sugammadex IBW [2 mg/kg IBW plus 4 mg/kg IBW]) as well as in all randomized treatment arms separated by depth of NMB (Sugammadex 2 mg/kg ABW, Sugammadex 4 mg/kg ABW, Sugammadex 2 mg/kg IBW, and Sugammadex 4 mg/kg IBW).

Percentage of Participants Experiencing an Adverse Event (AE) After Administration of Study Intervention

The percentage of participants experiencing an AE following administration of study intervention was monitored. An AE is any unfavorable and unintended medical occurrence, symptom, or disease witnessed in a participant, regardless of whether or not a causal relationship with the study treatment can be demonstrated. Further, any worsening (i.e. any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the study treatment is also considered an AE. As specified by the protocol, analyses for this outcome measure were conducted in participants pooled by dosing method across depth of NMB (Sugammadex ABW [2 mg/kg ABW plus 4 mg/kg ABW] and Sugammadex IBW [2 mg/kg IBW plus 4 mg/kg IBW]) as well as in all randomized treatment arms separated by depth of NMB (Sugammadex 2 mg/kg ABW, Sugammadex 4 mg/kg ABW, Sugammadex 2 mg/kg IBW, and Sugammadex 4 mg/kg IBW).

Percentage of Participants Experiencing a Serious Adverse Event (SAE) After Administration of Study Intervention

The percentage of participants experiencing an SAE following administration of study intervention was monitored. An SAE is an adverse event that: results in death; is life threatening; results in persistent or significant disability or incapacity; results in or prolongs a hospitalization; is a congenital anomaly or birth defect; is a cancer; or may jeopardize the participant, potentially requiring medical or surgical intervention. As specified by the protocol, analyses for this outcome measure were conducted in participants pooled by dosing method across depth of NMB (Sugammadex ABW [2 mg/kg ABW plus 4 mg/kg ABW] and Sugammadex IBW [2 mg/kg IBW plus 4 mg/kg IBW]) as well as in all randomized treatment arms separated by depth of NMB (Sugammadex 2 mg/kg ABW, Sugammadex 4 mg/kg ABW, Sugammadex 2 mg/kg IBW, and Sugammadex 4 mg/kg IBW).

Percentage of Participants Experiencing an Event of Clinical Interest (ECI) After Administration of Study Intervention

The percentage of participants experiencing an ECI following administration of study intervention was monitored. ECIs are a discrete set of both AEs and SAEs, specifically designated as such for the trial. For the purposes of this investigation, ECIs included 1) drug-induced liver injury; 2) clinically-relevant arrhythmias, inclusive of bradycardia and tachycardia defined as events necessitating intervention, as determined by investigator judgment; and 3) instances of hypersensitivity and/or anaphylaxis adjudicated by an external expert Adjudication Committee. As specified by the protocol, analyses for this outcome measure were conducted in participants pooled by dosing method across depth of NMB (Sugammadex ABW [2 mg/kg ABW plus 4 mg/kg ABW] and Sugammadex IBW [2 mg/kg IBW plus 4 mg/kg IBW]) as well as in all randomized treatment arms separated by depth of NMB (Sugammadex 2 mg/kg ABW, Sugammadex 4 mg/kg ABW, Sugammadex 2 mg/kg IBW, and Sugammadex 4 mg/kg IBW).

Secondary Outcome Measures

Percentage of Participants With Prolonged (>10 Minutes) Time to Recovery (TTR) of the Train Of Four (TOF) Ratio to ≥0.9

Following administration of study intervention, the percentage of participants experiencing prolonged (>10 minutes) recovery to a TOF ratio ≥0.9 was calculated. TTR was monitored by applying electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to magnitudes of the first and fourth twitches respectively, after nerve stimulation. The T4/T1 ratio (TOF; expressed as a decimal of up to 1.0) indicates the extent of recovery from NMB. A faster TTR of the TOF ratio to 0.9 indicates faster recovery from NMB. As specified by the protocol, analyses for this outcome measure were conducted in participants pooled by dosing method across depth of NMB (Sugammadex ABW [2 mg/kg ABW plus 4 mg/kg ABW] and Sugammadex IBW [2 mg/kg IBW plus 4 mg/kg IBW]) as well as in all randomized treatment arms separated by depth of NMB (Sugammadex 2 mg/kg ABW, Sugammadex 4 mg/kg ABW, Sugammadex 2 mg/kg IBW, and Sugammadex 4 mg/kg IBW).

Time to Recovery (TTR) of Participant Train of Four (TOF) Ratio to ≥0.9: Secondary Geometric Mean Analysis

The secondary efficacy analysis of TTR of participant TOF ratio to ≥0.9 was performed by estimating the geometric mean of TTR within each treatment group. TTR was monitored by applying electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to magnitudes of the first and fourth twitches respectively, after nerve stimulation. The T4/T1 ratio (TOF; expressed as a decimal of up to 1.0) indicates the extent of recovery from NMB. A faster TTR of the TOF ratio to 0.9 indicates faster recovery from NMB. As specified by the protocol, analyses for this outcome measure were conducted in participants pooled by dosing method across depth of NMB (Sugammadex ABW [2 mg/kg ABW plus 4 mg/kg ABW] and Sugammadex IBW [2 mg/kg IBW plus 4 mg/kg IBW]) as well as in all randomized treatment arms separated by depth of NMB (Sugammadex 2 mg/kg ABW, Sugammadex 4 mg/kg ABW, Sugammadex 2 mg/kg IBW, and Sugammadex 4 mg/kg IBW).

Time to Recovery (TTR) of Participant Train of Four (TOF) Ratio to ≥0.8: Geometric Mean Analysis

The efficacy analysis of TTR of participant TOF ratio to ≥0.8 was performed by estimating the geometric mean of TTR within each treatment group. TTR was monitored by applying electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to magnitudes of the first and fourth twitches respectively, after nerve stimulation. The T4/T1 ratio (TOF; expressed as a decimal of up to 1.0) indicates the extent of recovery from NMB. A faster TTR of the TOF ratio to 0.8 indicates faster recovery from NMB. As specified by the protocol, analyses for this outcome measure were conducted in participants pooled by dosing method across depth of NMB (Sugammadex ABW [2 mg/kg ABW plus 4 mg/kg ABW] and Sugammadex IBW [2 mg/kg IBW plus 4 mg/kg IBW]) as well as in all randomized treatment arms separated by depth of NMB (Sugammadex 2 mg/kg ABW, Sugammadex 4 mg/kg ABW, Sugammadex 2 mg/kg IBW, and Sugammadex 4 mg/kg IBW).

Time to Recovery (TTR) of Participant Train of Four (TOF) Ratio to ≥0.7: Geometric Mean Analysis

The efficacy analysis of TTR of participant TOF ratio to ≥0.7 was performed by estimating the geometric mean of TTR within each treatment group. TTR was monitored by applying electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to magnitudes of the first and fourth twitches respectively, after nerve stimulation. The T4/T1 ratio (TOF; expressed as a decimal of up to 1.0) indicates the extent of recovery from NMB. A faster TTR of the TOF ratio to 0.7 indicates faster recovery from NMB. As specified by the protocol, analyses for this outcome measure were conducted in participants pooled by dosing method across depth of NMB (Sugammadex ABW [2 mg/kg ABW plus 4 mg/kg ABW] and Sugammadex IBW [2 mg/kg IBW plus 4 mg/kg IBW]) as well as in all randomized treatment arms separated by depth of NMB (Sugammadex 2 mg/kg ABW, Sugammadex 4 mg/kg ABW, Sugammadex 2 mg/kg IBW, and Sugammadex 4 mg/kg IBW).

Full Information

NCT ID

NCT03346070

First Posted

November 15, 2017

Last Updated

January 12, 2021

Sponsor

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT03346070

Brief Title

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)

Official Title

A Phase 4 Randomized, Active-Comparator Controlled Trial to Study the Efficacy and Safety of Sugammadex (MK-8616) for the Reversal of Neuromuscular Blockade Induced by Either Rocuronium Bromide or Vecuronium Bromide in Morbidly Obese Subjects

Study Type

Interventional

2. Study Status

Record Verification Date

January 2021

Overall Recruitment Status

Completed

Study Start Date

January 1, 2018 (Actual)

Primary Completion Date

January 29, 2019 (Actual)

Study Completion Date

January 29, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neuromuscular Blockade

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

207 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sugammadex 2 mg/kg ABW

Arm Type

Experimental

Arm Description

Arm Title

Sugammadex 2 mg/kg IBW

Arm Type

Experimental

Arm Description

Arm Title

Sugammadex 4 mg/kg ABW

Arm Type

Experimental

Arm Description

Arm Title

Sugammadex 4 mg/kg IBW

Arm Type

Experimental

Arm Description

Arm Title

Neostigmine/Glycopyrrolate

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Sugammadex 2 mg/kg ABW

Other Intervention Name(s)

MK-8616

Intervention Description

Following administration of NMBA (Rocuronium or Vecuronium) to achieve moderate NMB, participants received a single i.v. bolus of Sugammadex (2 mg/kg by ABW) for reversal of moderate NMB. Moderate NMB is defined as the reappearance of a second twitch (T2) in response to TOF stimulations.

Intervention Type

Drug

Intervention Name(s)

Sugammadex 2 mg/kg IBW

Other Intervention Name(s)

MK-8616

Intervention Description

Following administration of NMBA (Rocuronium or Vecuronium) to achieve moderate NMB, participants received a single i.v. bolus of Sugammadex (2 mg/kg by IBW) for reversal of moderate NMB. Moderate NMB is defined as the reappearance of T2 in response to TOF stimulations.

Intervention Type

Drug

Intervention Name(s)

Sugammadex 4 mg/kg ABW

Other Intervention Name(s)

MK-8616

Intervention Description

Following administration of NMBA (Rocuronium or Vecuronium) to achieve deep NMB, participants received a single i.v. bolus of Sugammadex (4 mg/kg by ABW) for reversal of deep NMB. Deep NMB is defined as no response to TOF stimulations (TOF=0) and a detection target of 1-2 post-tetanic counts (PTCs).

Intervention Type

Drug

Intervention Name(s)

Sugammadex 4 mg/kg IBW

Other Intervention Name(s)

MK-8616

Intervention Description

Following administration of NMBA (Rocuronium or Vecuronium) to achieve deep NMB, participants will receive a single i.v. bolus of Sugammadex (4 mg/kg by IBW) for reversal of deep NMB. Deep NMB is defined as no response to TOF stimulations (TOF=0) and a detection target of 1-2 post-tetanic counts (PTCs).

Intervention Type

Drug

Intervention Name(s)

Neostigmine + Glycopyrrolate

Intervention Description

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), dosed according to participant ABW for reversal of moderate NMB. Moderate NMB is defined as the reappearance of T2 in response to TOF stimulations.

Intervention Type

Drug

Intervention Name(s)

Rocuronium or Vecuronium

Intervention Description

To achieve NMB, participants received steroidal NMBA Rocuronium Bromide or Vecuronium Bromide administered via i.v. infusion and dosed according to participant ABW. NMBAs were concomitant medications used per label as adjunct to general anesthesia.

Primary Outcome Measure Information:

Title

Time to Recovery (TTR) of Participant Train Of Four (TOF) Ratio to ≥0.9: Primary Kaplan-Meier Analysis

Description

Time Frame

Up to 76 minutes

Title

Percentage of Participants With Treatment-Emergent Sinus Bradycardia Events

Description

Time Frame

Up to 35 minutes

Title

Percentage of Participants With Treatment-Emergent Sinus Tachycardia Events

Description

Time Frame

Up to 35 minutes

Title

Percentage of Participants With Other Treatment-Emergent Cardiac Arrhythmia Events

Description

Time Frame

Up to 35 minutes

Title

Percentage of Participants Experiencing an Adverse Event (AE) After Administration of Study Intervention

Description

Time Frame

Up to 7 days

Title

Percentage of Participants Experiencing a Serious Adverse Event (SAE) After Administration of Study Intervention

Description

Time Frame

Up to 7 days

Title

Percentage of Participants Experiencing an Event of Clinical Interest (ECI) After Administration of Study Intervention

Description

Time Frame

Up to 7 days

Secondary Outcome Measure Information:

Title

Percentage of Participants With Prolonged (>10 Minutes) Time to Recovery (TTR) of the Train Of Four (TOF) Ratio to ≥0.9

Description

Time Frame

Up to 76 minutes

Title

Time to Recovery (TTR) of Participant Train of Four (TOF) Ratio to ≥0.9: Secondary Geometric Mean Analysis

Description

Time Frame

Up to 76 minutes

Title

Time to Recovery (TTR) of Participant Train of Four (TOF) Ratio to ≥0.8: Geometric Mean Analysis

Description

Time Frame

Up to 69 minutes

Title

Time to Recovery (TTR) of Participant Train of Four (TOF) Ratio to ≥0.7: Geometric Mean Analysis

Description

Time Frame

Up to 61 minutes

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Merck Sharp & Dohme LLC

Official's Role

Study Director

Facility Information:

Facility Name

University California / Davis ( Site 2001)

City

Sacramento

State/Province

California

ZIP/Postal Code

95817

Country

United States

Facility Name

Jackson Memorial Hospital/University of Miami ( Site 2007)

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Facility Name

University of Kansas Medical Center ( Site 2049)

City

Kansas City

State/Province

Kansas

ZIP/Postal Code

66160

Country

United States

Facility Name

William Beaumont Hospital - Royal Oak ( Site 2033)

City

Royal Oak

State/Province

Michigan

ZIP/Postal Code

48073

Country

United States

Facility Name

University Hospital- Columbia MO ( Site 2060)

City

Columbia

State/Province

Missouri

ZIP/Postal Code

65212

Country

United States

Facility Name

Robert Wood Johnson University Hospital ( Site 2037)

City

New Brunswick

State/Province

New Jersey

ZIP/Postal Code

08901

Country

United States

Facility Name

Mission Hospital - St. Joseph ( Site 2015)

City

Asheville

State/Province

North Carolina

ZIP/Postal Code

28801

Country

United States

Facility Name

Cleveland Clinic Foundation ( Site 2031)

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44195

Country

United States

Facility Name

Temple University Hospital ( Site 2004)

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19140

Country

United States

Facility Name

Vanderbilt University Medical Center ( Site 2032)

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232

Country

United States

Facility Name

Hermann Drive Surgical Center ( Site 2020)

City

Houston

State/Province

Texas

ZIP/Postal Code

77004

Country

United States

Facility Name

Hermann Drive Surgical Center ( Site 2059)

City

Houston

State/Province

Texas

ZIP/Postal Code

77004

Country

United States

Facility Name

Zablocki VA Medical Center ( Site 2011)

City

Milwaukee

State/Province

Wisconsin

ZIP/Postal Code

53295

Country

United States

Facility Name

Sozialmedizinisches Zentrum Ost - Donauspital ( Site 2150)

City

Wien

ZIP/Postal Code

1220

Country

Austria

Facility Name

Universitaire Ziekenhuis Antwerpen - UZA ( Site 2200)

City

Edegem

ZIP/Postal Code

2650

Country

Belgium

Facility Name

Bispebjerg og Frederiksberg Hospital ( Site 2250)

City

Copenhagen NV

ZIP/Postal Code

2400

Country

Denmark

Facility Name

Rigshospitalet ( Site 2253)

City

Copenhagen

ZIP/Postal Code

2100

Country

Denmark

Facility Name

Johanniter Krankenhaus Bonn ( Site 2353)

City

Bonn

ZIP/Postal Code

53113

Country

Germany

Facility Name

Diakovere Annastift gGmbH ( Site 2355)

City

Hannover

ZIP/Postal Code

30625

Country

Germany

Facility Name

Universitatsklinikum Giessen und Marburg GmbH ( Site 2356)

City

Marburg

ZIP/Postal Code

35043

Country

Germany

Facility Name

Klinikum Rechts der Isar Technische Universitaet Muenchen ( Site 2350)

City

Muenchen

ZIP/Postal Code

81675

Country

Germany

Facility Name

St. Franziskus-Hospital ( Site 2354)

City

Muenster

ZIP/Postal Code

48145

Country

Germany

Facility Name

Klinikum am Steinenberg Reutlingen ( Site 2352)

City

Reutlingen

ZIP/Postal Code

72764

Country

Germany

Facility Name

Josephs-Hospitals Warendorf ( Site 2351)

City

Warendorf

ZIP/Postal Code

48231

Country

Germany

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

IPD Sharing URL

http://engagezone.msd.com/ds_documentation.php

Citations:

PubMed Identifier

33278332

Citation

Mostoller K, Wrishko R, Maganti L, Herring WJ, van Zutphen-van Geffen M. Pharmacokinetics of Sugammadex Dosed by Actual and Ideal Body Weight in Patients With Morbid Obesity Undergoing Surgery. Clin Transl Sci. 2021 Mar;14(2):737-744. doi: 10.1111/cts.12941. Epub 2020 Dec 16.

Results Reference

background

PubMed Identifier

33639839

Citation

Horrow JC, Li W, Blobner M, Lombard J, Speek M, DeAngelis M, Herring WJ. Actual versus ideal body weight dosing of sugammadex in morbidly obese patients offers faster reversal of rocuronium- or vecuronium-induced deep or moderate neuromuscular block: a randomized clinical trial. BMC Anesthesiol. 2021 Feb 27;21(1):62. doi: 10.1186/s12871-021-01278-w.

Results Reference

derived

Learn more about this trial

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)

We'll reach out to this number within 24 hrs