Neuromuscular BlockadePhase 4NCT03346070
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)
A Phase 4 study testing Sugammadex 2 mg/kg ABW, Sugammadex 2 mg/kg IBW and Sugammadex 4 mg/kg ABW in people with Neuromuscular Blockade, run by Merck Sharp & Dohme LLC at 24 sites in 5 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuromuscular Blockade
- What is being tested?
- Sugammadex 2 mg/kg ABW, Sugammadex 2 mg/kg IBW and Sugammadex 4 mg/kg ABW
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 207 participants
- Where
- 24 sitesin 5 countries
- Study dates
- 1 Jan 2018to 29 Jan 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
24 sites in 5 countries.
24 sites in 5 countries
United States13 sites
Mission Hospital - St. Joseph ( Site 2015)
Asheville, North Carolina, 28801
Cleveland Clinic Foundation ( Site 2031)
Cleveland, Ohio, 44195
University Hospital- Columbia MO ( Site 2060)
Columbia, Missouri, 65212
Hermann Drive Surgical Center ( Site 2020)
Houston, Texas, 77004
Hermann Drive Surgical Center ( Site 2059)
Houston, Texas, 77004
University of Kansas Medical Center ( Site 2049)
Kansas City, Kansas, 66160
Jackson Memorial Hospital/University of Miami ( Site 2007)
Miami, Florida, 33136
Zablocki VA Medical Center ( Site 2011)
Milwaukee, Wisconsin, 53295
Vanderbilt University Medical Center ( Site 2032)
Nashville, Tennessee, 37232
Robert Wood Johnson University Hospital ( Site 2037)
New Brunswick, New Jersey, 08901
Temple University Hospital ( Site 2004)
Philadelphia, Pennsylvania, 19140
William Beaumont Hospital - Royal Oak ( Site 2033)
Royal Oak, Michigan, 48073
University California / Davis ( Site 2001)
Sacramento, California, 95817
Germany7 sites
Johanniter Krankenhaus Bonn ( Site 2353)
Bonn, 53113
Diakovere Annastift gGmbH ( Site 2355)
Hanover, 30625
Universitatsklinikum Giessen und Marburg GmbH ( Site 2356)
Marburg, 35043
Klinikum Rechts der Isar Technische Universitaet Muenchen ( Site 2350)
München, 81675
St. Franziskus-Hospital ( Site 2354)
Münster, 48145
Klinikum am Steinenberg Reutlingen ( Site 2352)
Reutlingen, 72764
Josephs-Hospitals Warendorf ( Site 2351)
Warendorf, 48231
Denmark2 sites
Rigshospitalet ( Site 2253)
Copenhagen, 2100
Bispebjerg og Frederiksberg Hospital ( Site 2250)
Copenhagen NV, 2400
Austria1 site
Sozialmedizinisches Zentrum Ost - Donauspital ( Site 2150)
Vienna, 1220
Belgium1 site
Universitaire Ziekenhuis Antwerpen - UZA ( Site 2200)
Edegem, 2650
About this study
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
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
- Being tested
- Sugammadex 2 mg/kg ABW, Sugammadex 2 mg/kg IBW, Sugammadex 4 mg/kg ABW, Sugammadex 4 mg/kg IBW, Neostigmine + Glycopyrrolate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sugammadex 2 mg/kg ABWDrug
Also called MK-8616
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.
Sugammadex 2 mg/kg IBWDrug
Also called MK-8616
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.
Sugammadex 4 mg/kg ABWDrug
Also called MK-8616
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).
Sugammadex 4 mg/kg IBWDrug
Also called MK-8616
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).
Neostigmine + GlycopyrrolateDrug
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 VecuroniumDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Sugammadex 2 mg/kg ABW | Experimental | 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. Receives: Drug: Sugammadex 2 mg/kg ABW; Drug: Rocuronium or Vecuronium |
| Sugammadex 2 mg/kg IBW | Experimental | 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. Receives: Drug: Sugammadex 2 mg/kg IBW; Drug: Rocuronium or Vecuronium |
| Sugammadex 4 mg/kg ABW | Experimental | 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. Receives: Drug: Sugammadex 4 mg/kg ABW; Drug: Rocuronium or Vecuronium |
| Sugammadex 4 mg/kg IBW | Experimental | 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. Receives: Drug: Sugammadex 4 mg/kg IBW; Drug: Rocuronium or Vecuronium |
| Neostigmine/Glycopyrrolate | Active comparator | 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. Receives: Drug: Neostigmine + Glycopyrrolate; Drug: Rocuronium or Vecuronium |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Up to 76 minutes
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).
Measured: Up to 35 minutes
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).
Measured: Up to 35 minutes
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).
Measured: Up to 35 minutes
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).
Measured: Up to 7 days
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).
Measured: Up to 7 days
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).
Measured: Up to 7 days
Secondary outcomes (4)
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).
Measured: Up to 76 minutes
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).
Measured: Up to 76 minutes
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).
Measured: Up to 69 minutes
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).
Measured: Up to 61 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2017
- Study start1 Jan 2018
- Primary completion29 Jan 2019
- Study completion29 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Neuromuscular BlockadeStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 207 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03346070
- Sponsor's protocol ID
- 8616-146
- Other IDs
- 2017-000188-33, MK-8616-146, 2017
- Status last verified
- Jan 2021
- First submitted
- 15 Nov 2017
- Last updated
- 28 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
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.
PubMed 33278332Horrow 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.
PubMed 33639839
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03346070
- Acronym / sponsor ID
- 8616-146
- Conditions
- Neuromuscular Blockade
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 207 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 29 Jan 2019 (actual)
- Study completion
- 29 Jan 2019 (actual)
- First posted
- 17 Nov 2017 (actual)
- Results
- Posted 23 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Sugammadex 2 mg/kg ABW | Experimental | Drug: Sugammadex 2 mg/kg ABW, Drug: Rocuronium or VecuroniumFollowing 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. |
| Sugammadex 2 mg/kg IBW | Experimental | Drug: Sugammadex 2 mg/kg IBW, Drug: Rocuronium or VecuroniumFollowing 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. |
| Sugammadex 4 mg/kg ABW | Experimental | Drug: Sugammadex 4 mg/kg ABW, Drug: Rocuronium or VecuroniumFollowing 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. |
| Sugammadex 4 mg/kg IBW | Experimental | Drug: Sugammadex 4 mg/kg IBW, Drug: Rocuronium or VecuroniumFollowing 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. |
| Neostigmine/Glycopyrrolate | Active comparator | Drug: Neostigmine + Glycopyrrolate, Drug: Rocuronium or VecuroniumFollowing 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sugammadex 2 mg/kg ABWAlso: MK-8616Following 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. | Drug | Sugammadex 2 mg/kg ABW |
| Sugammadex 2 mg/kg IBWAlso: MK-8616Following 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. | Drug | Sugammadex 2 mg/kg IBW |
| Sugammadex 4 mg/kg ABWAlso: MK-8616Following 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). | Drug | Sugammadex 4 mg/kg ABW |
| Sugammadex 4 mg/kg IBWAlso: MK-8616Following 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). | Drug | Sugammadex 4 mg/kg IBW |
| Neostigmine + GlycopyrrolateFollowing 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. | Drug | Neostigmine/Glycopyrrolate |
| Rocuronium or VecuroniumTo 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. | Drug | Neostigmine/Glycopyrrolate, Sugammadex 2 mg/kg ABW, Sugammadex 2 mg/kg IBW, Sugammadex 4 mg/kg ABW, Sugammadex 4 mg/kg IBW |
Primary outcome
Time to Recovery (TTR) of Participant Train Of Four (TOF) Ratio to ≥0.9: Primary Kaplan-Meier Analysis
Time frame: Up to 76 minutes
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
Time frame: Up to 35 minutes
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
Time frame: Up to 35 minutes
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
Time frame: Up to 35 minutes
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
Time frame: Up to 7 days
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
Time frame: Up to 7 days
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
Time frame: Up to 7 days
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).
4 secondary outcomes
Percentage of Participants With Prolonged (>10 Minutes) Time to Recovery (TTR) of the Train Of Four (TOF) Ratio to ≥0.9
Time frame: Up to 76 minutes
Time to Recovery (TTR) of Participant Train of Four (TOF) Ratio to ≥0.9: Secondary Geometric Mean Analysis
Time frame: Up to 76 minutes
Time to Recovery (TTR) of Participant Train of Four (TOF) Ratio to ≥0.8: Geometric Mean Analysis
Time frame: Up to 69 minutes
Time to Recovery (TTR) of Participant Train of Four (TOF) Ratio to ≥0.7: Geometric Mean Analysis
Time frame: Up to 61 minutes
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 33278332Mostoller 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.
- Derived from this study: PubMed 33639839Horrow 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.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
24 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sugammadex 2 mg/kg ABW, Sugammadex 2 mg/kg IBW and Sugammadex 4 mg/kg ABW in people with Neuromuscular Blockade, run by Merck Sharp & Dohme LLC at 24 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States, Germany, Denmark, Austria, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Recovery (TTR) of Participant Train Of Four (TOF) Ratio to ≥0.9: Primary Kaplan-Meier Analysis (time frame: Up to 76 minutes). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03346070, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2021.