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)

NCT ID: NCT03346070

Last Updated: 2021-01-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 207 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-01
• Study Completion Date: 2019-01-29

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.

Conditions

Neuromuscular Blockade

Study Design

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

Study Groups

Sugammadex 2 mg/kg ABW

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.

Group Type: EXPERIMENTAL

Sugammadex 2 mg/kg ABW

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 by ABW) for reversal of moderate NMB.

Moderate NMB is defined as the reappearance of a second twitch (T2) in response to TOF stimulations.

Rocuronium or Vecuronium

Intervention Type: DRUG

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.

Sugammadex 2 mg/kg IBW

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.

Group Type: EXPERIMENTAL

Sugammadex 2 mg/kg IBW

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 by IBW) for reversal of moderate NMB.

Moderate NMB is defined as the reappearance of T2 in response to TOF stimulations.

Rocuronium or Vecuronium

Intervention Type: DRUG

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.

Sugammadex 4 mg/kg ABW

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.

Group Type: EXPERIMENTAL

Sugammadex 4 mg/kg ABW

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 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).

Rocuronium or Vecuronium

Intervention Type: DRUG

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.

Sugammadex 4 mg/kg IBW

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.

Group Type: EXPERIMENTAL

Sugammadex 4 mg/kg IBW

Intervention Type: DRUG

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).

Rocuronium or Vecuronium

Intervention Type: DRUG

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.

Neostigmine/Glycopyrrolate

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.

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), dosed according to participant ABW for reversal of moderate NMB.

Moderate NMB is defined as the reappearance of T2 in response to TOF stimulations.

Rocuronium or Vecuronium

Intervention Type: DRUG

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.

Interventions

Sugammadex 2 mg/kg ABW

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

Sugammadex 2 mg/kg IBW

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

Sugammadex 4 mg/kg ABW

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

Sugammadex 4 mg/kg IBW

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

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), 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

Rocuronium or Vecuronium

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.

Intervention Type: DRUG

Other Intervention Names

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

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.

• 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 California / Davis ( Site 2001)

Sacramento, California, United States

Jackson Memorial Hospital/University of Miami ( Site 2007)

Miami, Florida, United States

University of Kansas Medical Center ( Site 2049)

Kansas City, Kansas, United States

William Beaumont Hospital - Royal Oak ( Site 2033)

Royal Oak, Michigan, United States

University Hospital- Columbia MO ( Site 2060)

Columbia, Missouri, United States

Robert Wood Johnson University Hospital ( Site 2037)

New Brunswick, New Jersey, United States

Mission Hospital - St. Joseph ( Site 2015)

Asheville, North Carolina, United States

Cleveland Clinic Foundation ( Site 2031)

Cleveland, Ohio, United States

Temple University Hospital ( Site 2004)

Philadelphia, Pennsylvania, United States

Vanderbilt University Medical Center ( Site 2032)

Nashville, Tennessee, United States

Hermann Drive Surgical Center ( Site 2020)

Houston, Texas, United States

Hermann Drive Surgical Center ( Site 2059)

Houston, Texas, United States

Zablocki VA Medical Center ( Site 2011)

Milwaukee, Wisconsin, United States

Sozialmedizinisches Zentrum Ost - Donauspital ( Site 2150)

Vienna, , Austria

Universitaire Ziekenhuis Antwerpen - UZA ( Site 2200)

Edegem, , Belgium

Rigshospitalet ( Site 2253)

Copenhagen, , Denmark

Bispebjerg og Frederiksberg Hospital ( Site 2250)

Copenhagen NV, , Denmark

Johanniter Krankenhaus Bonn ( Site 2353)

Bonn, , Germany

Diakovere Annastift gGmbH ( Site 2355)

Hanover, , Germany

Universitatsklinikum Giessen und Marburg GmbH ( Site 2356)

Marburg, , Germany

Klinikum Rechts der Isar Technische Universitaet Muenchen ( Site 2350)

München, , Germany

St. Franziskus-Hospital ( Site 2354)

Münster, , Germany

Klinikum am Steinenberg Reutlingen ( Site 2352)

Reutlingen, , Germany

Josephs-Hospitals Warendorf ( Site 2351)

Warendorf, , Germany

Countries

United States; Austria; Belgium; Denmark; Germany

References

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.

Reference Type: BACKGROUND

PMID: 33278332 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33639839 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-000188-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MK-8616-146

Identifier Type: OTHER

Identifier Source: secondary_id

8616-146

Identifier Type: -

Identifier Source: org_study_id