Clinical trial NCT03346070: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Neuromuscular Blockade
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2017-11-17
Enrollment: 207
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 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.


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.

Primary outcomes:
measure: Time to Recovery (TTR) of Participant Train Of Four (TOF) Ratio to ≥0.9: Primary Kaplan-Meier Analysis
timeFrame: Up to 76 minutes
measure: Percentage of Participants With Treatment-Emergent Sinus Bradycardia Events
timeFrame: Up to 35 minutes
measure: Percentage of Participants With Treatment-Emergent Sinus Tachycardia Events
timeFrame: Up to 35 minutes
measure: Percentage of Participants With Other Treatment-Emergent Cardiac Arrhythmia Events
timeFrame: Up to 35 minutes
measure: Percentage of Participants Experiencing an Adverse Event (AE) After Administration of Study Intervention
timeFrame: Up to 7 days
measure: Percentage of Participants Experiencing a Serious Adverse Event (SAE) After Administration of Study Intervention
timeFrame: Up to 7 days
measure: Percentage of Participants Experiencing an Event of Clinical Interest (ECI) After Administration of Study Intervention
timeFrame: Up to 7 days
Secondary outcomes:
measure: Percentage of Participants With Prolonged (>10 Minutes) Time to Recovery (TTR) of the Train Of Four (TOF) Ratio to ≥0.9
timeFrame: Up to 76 minutes
measure: Time to Recovery (TTR) of Participant Train of Four (TOF) Ratio to ≥0.9: Secondary Geometric Mean Analysis
timeFrame: Up to 76 minutes
measure: Time to Recovery (TTR) of Participant Train of Four (TOF) Ratio to ≥0.8: Geometric Mean Analysis
timeFrame: Up to 69 minutes
measure: Time to Recovery (TTR) of Participant Train of Four (TOF) Ratio to ≥0.7: Geometric Mean Analysis
timeFrame: Up to 61 minutes
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University California / Davis ( Site 2001)
state: California
city: Miami
country: United States
facility: Jackson Memorial Hospital/University of Miami ( Site 2007)
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Medical Center ( Site 2049)
state: Kansas
city: Royal Oak
country: United States
facility: William Beaumont Hospital - Royal Oak ( Site 2033)
state: Michigan
city: Columbia
country: United States
facility: University Hospital- Columbia MO ( Site 2060)
state: Missouri
city: New Brunswick
country: United States
facility: Robert Wood Johnson University Hospital ( Site 2037)
state: New Jersey
city: Asheville
country: United States
facility: Mission Hospital - St. Joseph ( Site 2015)
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation ( Site 2031)
state: Ohio
city: Philadelphia
country: United States
facility: Temple University Hospital ( Site 2004)
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center ( Site 2032)
state: Tennessee
city: Houston
country: United States
facility: Hermann Drive Surgical Center ( Site 2020)
state: Texas
city: Houston
country: United States
facility: Hermann Drive Surgical Center ( Site 2059)
state: Texas
city: Milwaukee
country: United States
facility: Zablocki VA Medical Center ( Site 2011)
state: Wisconsin
city: Wien
country: Austria
facility: Sozialmedizinisches Zentrum Ost - Donauspital ( Site 2150)
city: Edegem
country: Belgium
facility: Universitaire Ziekenhuis Antwerpen - UZA ( Site 2200)
city: Copenhagen NV
country: Denmark
facility: Bispebjerg og Frederiksberg Hospital ( Site 2250)
city: Copenhagen
country: Denmark
facility: Rigshospitalet ( Site 2253)
city: Bonn
country: Germany
facility: Johanniter Krankenhaus Bonn ( Site 2353)
city: Hannover
country: Germany
facility: Diakovere Annastift gGmbH ( Site 2355)
city: Marburg
country: Germany
facility: Universitatsklinikum Giessen und Marburg GmbH ( Site 2356)
city: Muenchen
country: Germany
facility: Klinikum Rechts der Isar Technische Universitaet Muenchen ( Site 2350)
city: Muenster
country: Germany
facility: St. Franziskus-Hospital ( Site 2354)
city: Reutlingen
country: Germany
facility: Klinikum am Steinenberg Reutlingen ( Site 2352)
city: Warendorf
country: Germany
facility: Josephs-Hospitals Warendorf ( Site 2351)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
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.
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.