Reversal of Neuromuscular Blockade
Conditions
Keywords
arrhythmia, bradycardia, neuromuscular blocking agents, surgery, tachycardia
Brief summary
The purpose of this trial is to evaluate the safety of sugammadex for the reversal of neuromuscular blockade (NMB) induced by neuromuscular blockade agents (NMBA) rocuronium or vecuronium in adult American Society of Anesthesiologists (ASA) Physical Status Class 3 and 4 participants. The primary objectives of the study are to characterize the incidence of treatment emergent sinus bradycardia, treatment emergent sinus tachycardia, or other treatment emergent cardiac arrhythmias after administration of sugammadex and to evaluate the general safety of sugammadex in a population of ASA Class 3 and 4 participants in a surgical setting.
Interventions
Following administration of NMBA (Rocuronium) to achieve deep NMB, participants received a single i.v. bolus of Sugammadex 16 mg/kg for reversal of deep NMB. Deep block is a level of NMB in which peripheral nerve stimulation elicits no muscle twitches and high-frequency muscle stimulation elicits minimal levels of muscle contraction.
Following administration of NMBA (Rocuronium or Vecuronium) to achieve moderate NMB, participants received a single i.v. bolus of Sugammadex 2 mg/kg for reversal of moderate NMB. Moderate block is a level of NMB in which peripheral nerve stimulation elicits one to four muscle twitches.
Following administration of NMBA (Rocuronium or Vecuronium) to achieve deep NMB, participants received a single i.v. bolus of Sugammadex 4 mg/kg for reversal of deep NMB. Deep block is a level of NMB in which peripheral nerve stimulation elicits no muscle twitches and high-frequency muscle stimulation elicits minimal levels of muscle contraction.
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) for reversal of moderate NMB. Moderate block is a level of NMB in which peripheral nerve stimulation elicits one to four muscle twitches.
DRUGRocuronium
To achieve NMB, participants received steroidal NMBA Rocuronium Bromide administered via IV infusion and dosed according to participant body weight. NMBAs were concomitant medications used per label and at Investigator's discretion as an adjunct to general anesthesia.
DRUGVecuronium
To achieve NMB, participants received steroidal NMBA Vecuronium Bromide administered via IV infusion and dosed according to participant body weight. NMBAs were concomitant medications used per label and at Investigator's discretion as an adjunct to general anesthesia.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has a body mass index (BMI) \< 40 kg/m2. * Is categorized as ASA Physical Status Class 3 or 4, as determined by the Investigator. * Has a planned surgical procedure that requires NMB with either rocuronium or vecuronium. * Has a planned surgical procedure (e.g., gastrointestinal, urologic, or laparoscopic) that in the opinion of the investigator does not preclude maintenance of moderate or deep depth of NMB throughout the case. * If female who is not of reproductive potential, is one of the following: (1) postmenopausal; (2) has had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion at least 6 weeks prior to screening; (3) has a congenital or acquired condition that prevents childbearing; or (4) is undergoing surgical sterilization (e.g., hysterectomy or tubal ligation) as the planned surgical procedure associated with participation in this study. * If female who is sexually active and of child-bearing potential, agrees to use a medically accepted method of contraception through seven days after receiving protocol-specified medication. Abstinence (relative to heterosexual activity) can be used as the sole method of contraception if it is consistently employed as the subject's preferred and usual lifestyle and if considered acceptable by local regulatory agencies and Ethics Review Committees/Institutional Review Boards. * Is able to provide (or the participant's legally authorized representative, in accordance with local requirements), written informed consent for the trial. The participant or legally authorized representative may also provide consent for Future Biomedical Research.
Exclusion criteria
* Has a pacemaker or automatic implantable cardioverter-defibrillator that precludes the assessment of bradycardia or arrhythmias. * Has a medical condition or surgical procedure that precludes reversal of neuromuscular block at the end of surgery. * Has a neuromuscular disorder(s) that may affect neuromuscular block and/or trial assessments. * Is dialysis-dependent or has severe renal insufficiency, defined as estimated creatinine clearance of \<30 mL/min. * Has or is suspected of having a personal history or family history (parents, grandparents, or siblings) of malignant hyperthermia. * Has or is suspected of having an allergy (e.g., hypersensitivity and/or anaphylactic reaction) to study treatments or its/their excipients, to opioids/opiates, muscle relaxants or their excipients, or other medication(s) used during general anesthesia. * Has received or is planned to receive toremifene within 24 hours before or within 24 hours after study medication administration. * Has any condition that would contraindicate the administration of study medication. * Is pregnant, is attempting to become pregnant, or is lactating. * Is currently participating in or has participated in an interventional clinical trial (including any other current or ongoing trial with a sugammadex treatment arm) with an investigational compound or device within 30 days of signing the informed consent form of this current trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-Emergent Sinus Bradycardia Events | Up to approximately 35 minutes post-administration | The percentage of participants experiencing treatment-emergent sinus bradycardia events was identified with continuous electrocardiogram (ECG) monitoring. Treatment-emergent sinus bradycardia were 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 have been considered an adverse event (AE), as determined by investigator judgment. |
| Percentage of Participants With Treatment-Emergent Sinus Tachycardia Events | Up to approximately 35 minutes post-administration | The percentage of participants experiencing treatment-emergent sinus tachycardia events was 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 have been considered an AE, as determined by investigator judgment. |
| Percentage of Participants With Other Treatment-Emergent Cardiac Arrhythmia Events | Up to approximately 35 minutes post-administration | The percentage of participants experiencing other treatment-emergent cardiac arrhythmia events was identified with continuous ECG monitoring. Other treatment-emergent cardiac arrhythmias were defined as new or worsening arrhythmias (e.g., atrial fibrillation, atrial tachycardia, ventricular fibrillation, or ventricular tachyarrhythmia), sustained for at least 1 minute after administration of study intervention. Worsening arrhythmia events may or may not have been considered an AE, as determined by investigator judgment. |
| Percentage of Participants Experiencing an Adverse Event (AE) Up To 7 Days After Administration of Study Intervention | Up to 7 days | As per the protocol primary analysis, the percentage of participants experiencing an AE up to 7 days after administration of study intervention was reported. An AE was defined as any untoward medical occurrence in a participant which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. |
| Percentage of Participants Experiencing a Serious Adverse Event (SAE) Up To 7 Days After Administration of Study Intervention | Up to 7 days | As per the protocol primary analysis, the percentage of participants experiencing an SAE up to 7 days after administration of study intervention was reported. An SAE was an adverse event that: resulted in death; was life threatening; resulted in persistent or significant disability or incapacity; resulted in or prolonged an existing inpatient hospitalization; was a congenital anomaly or birth defect; was an other important medical event, was a cancer; or was associated with an overdose. |
| Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Up to 7 days | As per the protocol primary analysis, the percentage of participants experiencing an ECI up to 7 days after administration of study intervention was reported. ECIs were 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. A participant could have experienced more than one type of ECI. |
Countries
Austria, Denmark, Germany, United States
Participant flow
Pre-assignment details
Of 344 participants randomized to the study, 331 received at least one dose of study treatment (All Treated Population) and were evaluable for all safety analysis.
Participants by arm
| Arm | Count |
|---|---|
| Sugammadex 2 mg/kg Sugammadex 2 mg/kg administered as a single intravenous (IV) dose | 111 |
| Sugammadex 4 mg/kg Sugammadex 4 mg/kg administered as a single IV dose | 112 |
| Sugammadex 16 mg/kg Sugammadex 16 mg/kg administered as a single IV dose | 68 |
| Neostigmine + Glycopyrrolate Neostigmine 50 μg/kg (up to 5 mg maximum dose) plus glycopyrrolate 10 μg/kg (up to 1 mg maximum dose) administered as a single IV dose | 53 |
| Total | 344 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 1 | 2 | 0 | 0 |
| Overall Study | Ineligible For Study - Not Treated | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 2 | 1 | 0 |
| Overall Study | Physician Decision | 3 | 2 | 0 | 2 |
| Overall Study | Randomization Mistake - Not Treated | 1 | 1 | 0 | 0 |
| Overall Study | Renal Insufficiency - Not Treated | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Sugammadex 2 mg/kg | Sugammadex 4 mg/kg | Sugammadex 16 mg/kg | Neostigmine + Glycopyrrolate | Total |
|---|---|---|---|---|---|
| Age, Continuous | 69.5 Years STANDARD_DEVIATION 10.7 | 67.8 Years STANDARD_DEVIATION 12.1 | 69.4 Years STANDARD_DEVIATION 10 | 66.6 Years STANDARD_DEVIATION 10.9 | 68.5 Years STANDARD_DEVIATION 11.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 6 Participants | 0 Participants | 2 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 109 Participants | 105 Participants | 67 Participants | 51 Participants | 332 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Participant Stratifications Missing | 6 Participants | 3 Participants | 0 Participants | 1 Participants | 10 Participants |
| Participant Stratifications Rocuronium, ASA Class 3 | 50 Participants | 49 Participants | 51 Participants | 25 Participants | 175 Participants |
| Participant Stratifications Rocuronium, ASA Class 4 | 15 Participants | 18 Participants | 17 Participants | 8 Participants | 58 Participants |
| Participant Stratifications Vecuronium, ASA Class 3 | 29 Participants | 31 Participants | 0 Participants | 14 Participants | 74 Participants |
| Participant Stratifications Vecuronium, ASA Class 4 | 11 Participants | 11 Participants | 0 Participants | 5 Participants | 27 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 9 Participants | 2 Participants | 3 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 106 Participants | 103 Participants | 66 Participants | 50 Participants | 325 Participants |
| Sex: Female, Male Female | 50 Participants | 41 Participants | 29 Participants | 15 Participants | 135 Participants |
| Sex: Female, Male Male | 61 Participants | 71 Participants | 39 Participants | 38 Participants | 209 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 111 | 2 / 112 | 0 / 68 | 0 / 53 |
| other Total, other adverse events | 89 / 105 | 89 / 107 | 60 / 68 | 41 / 51 |
| serious Total, serious adverse events | 16 / 105 | 12 / 107 | 9 / 68 | 4 / 51 |
Outcome results
Primary
Percentage of Participants Experiencing an Adverse Event (AE) Up To 7 Days After Administration of Study Intervention
As per the protocol primary analysis, the percentage of participants experiencing an AE up to 7 days after administration of study intervention was reported. An AE was defined as any untoward medical occurrence in a participant which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE.
Time frame: Up to 7 days
Population: All randomized participants who received at least one dose of study intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sugammadex 2 mg/kg | Percentage of Participants Experiencing an Adverse Event (AE) Up To 7 Days After Administration of Study Intervention | 94.3 Percentage of participants |
| Sugammadex 4 mg/kg | Percentage of Participants Experiencing an Adverse Event (AE) Up To 7 Days After Administration of Study Intervention | 88.8 Percentage of participants |
| Sugammadex 16 mg/kg | Percentage of Participants Experiencing an Adverse Event (AE) Up To 7 Days After Administration of Study Intervention | 92.6 Percentage of participants |
| Neostigmine + Glycopyrrolate | Percentage of Participants Experiencing an Adverse Event (AE) Up To 7 Days After Administration of Study Intervention | 88.2 Percentage of participants |
Comparison: Miettinen \& Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval95% CI: [-2.6, 18.5]
Comparison: Miettinen \& Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval95% CI: [-9.3, 13.1]
Comparison: Miettinen \& Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval95% CI: [-8.4, 17.7]
Primary
Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention
As per the protocol primary analysis, the percentage of participants experiencing an ECI up to 7 days after administration of study intervention was reported. ECIs were 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. A participant could have experienced more than one type of ECI.
Time frame: Up to 7 days
Population: All randomized participants who received at least one dose of study intervention
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sugammadex 2 mg/kg | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | With one or more ECIs | 1.9 Percentage of Participants |
| Sugammadex 2 mg/kg | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Other Clinically Relevant Cardiac Arrhythmia | 0.0 Percentage of Participants |
| Sugammadex 2 mg/kg | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Clinically Relevant Tachycardia | 1.9 Percentage of Participants |
| Sugammadex 2 mg/kg | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Adjudicated Hypersensitivity | 0.0 Percentage of Participants |
| Sugammadex 2 mg/kg | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Drug Induced Liver Injury | 0.0 Percentage of Participants |
| Sugammadex 2 mg/kg | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Adjudicated Anaphylaxis | 0.0 Percentage of Participants |
| Sugammadex 2 mg/kg | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Clinically Relevant Bradycardia | 0.0 Percentage of Participants |
| Sugammadex 4 mg/kg | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Other Clinically Relevant Cardiac Arrhythmia | 0.9 Percentage of Participants |
| Sugammadex 4 mg/kg | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Clinically Relevant Bradycardia | 2.8 Percentage of Participants |
| Sugammadex 4 mg/kg | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Adjudicated Anaphylaxis | 0.0 Percentage of Participants |
| Sugammadex 4 mg/kg | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Clinically Relevant Tachycardia | 1.9 Percentage of Participants |
| Sugammadex 4 mg/kg | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Drug Induced Liver Injury | 0.0 Percentage of Participants |
| Sugammadex 4 mg/kg | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Adjudicated Hypersensitivity | 0.0 Percentage of Participants |
| Sugammadex 4 mg/kg | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | With one or more ECIs | 5.6 Percentage of Participants |
| Sugammadex 16 mg/kg | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Clinically Relevant Bradycardia | 0.0 Percentage of Participants |
| Sugammadex 16 mg/kg | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | With one or more ECIs | 7.4 Percentage of Participants |
| Sugammadex 16 mg/kg | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Adjudicated Hypersensitivity | 0.0 Percentage of Participants |
| Sugammadex 16 mg/kg | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Adjudicated Anaphylaxis | 0.0 Percentage of Participants |
| Sugammadex 16 mg/kg | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Clinically Relevant Tachycardia | 5.9 Percentage of Participants |
| Sugammadex 16 mg/kg | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Other Clinically Relevant Cardiac Arrhythmia | 1.5 Percentage of Participants |
| Sugammadex 16 mg/kg | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Drug Induced Liver Injury | 0.0 Percentage of Participants |
| Neostigmine + Glycopyrrolate | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Adjudicated Anaphylaxis | 0.0 Percentage of Participants |
| Neostigmine + Glycopyrrolate | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Drug Induced Liver Injury | 0.0 Percentage of Participants |
| Neostigmine + Glycopyrrolate | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Other Clinically Relevant Cardiac Arrhythmia | 2.0 Percentage of Participants |
| Neostigmine + Glycopyrrolate | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Adjudicated Hypersensitivity | 0.0 Percentage of Participants |
| Neostigmine + Glycopyrrolate | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | With one or more ECIs | 3.9 Percentage of Participants |
| Neostigmine + Glycopyrrolate | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Clinically Relevant Tachycardia | 0.0 Percentage of Participants |
| Neostigmine + Glycopyrrolate | Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention | Clinically Relevant Bradycardia | 2.0 Percentage of Participants |
Comparison: The percentage of participants experiencing one or more ECIs was compared between the Sugammadex 2 mg/kg arm and the Neostigmine plus Glycopyrrolate arm. Miettinen \& Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval95% CI: [-11.8, 3.8]
Comparison: The percentage of participants experiencing one or more ECIs was compared between the Sugammadex 4 mg/kg arm and the Neostigmine plus Glycopyrrolate arm. Miettinen \& Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval95% CI: [-8.1, 8.4]
Comparison: The percentage of participants experiencing one or more ECIs was compared between the Sugammadex 16 mg/kg arm and the Neostigmine plus Glycopyrrolate arm. Miettinen \& Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval95% CI: [-13.5, 11.1]
Primary
Percentage of Participants Experiencing a Serious Adverse Event (SAE) Up To 7 Days After Administration of Study Intervention
As per the protocol primary analysis, the percentage of participants experiencing an SAE up to 7 days after administration of study intervention was reported. An SAE was an adverse event that: resulted in death; was life threatening; resulted in persistent or significant disability or incapacity; resulted in or prolonged an existing inpatient hospitalization; was a congenital anomaly or birth defect; was an other important medical event, was a cancer; or was associated with an overdose.
Time frame: Up to 7 days
Population: All randomized participants who received at least one dose of study intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sugammadex 2 mg/kg | Percentage of Participants Experiencing a Serious Adverse Event (SAE) Up To 7 Days After Administration of Study Intervention | 11.4 Percentage of Participants |
| Sugammadex 4 mg/kg | Percentage of Participants Experiencing a Serious Adverse Event (SAE) Up To 7 Days After Administration of Study Intervention | 7.5 Percentage of Participants |
| Sugammadex 16 mg/kg | Percentage of Participants Experiencing a Serious Adverse Event (SAE) Up To 7 Days After Administration of Study Intervention | 10.3 Percentage of Participants |
| Neostigmine + Glycopyrrolate | Percentage of Participants Experiencing a Serious Adverse Event (SAE) Up To 7 Days After Administration of Study Intervention | 5.9 Percentage of Participants |
Comparison: Miettinen \& Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval95% CI: [-5.5, 14.3]
Comparison: Miettinen \& Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval95% CI: [-9.2, 9.3]
Comparison: Miettinen \& Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval95% CI: [-15.1, 12.7]
Primary
Percentage of Participants With Other Treatment-Emergent Cardiac Arrhythmia Events
The percentage of participants experiencing other treatment-emergent cardiac arrhythmia events was identified with continuous ECG monitoring. Other treatment-emergent cardiac arrhythmias were defined as new or worsening arrhythmias (e.g., atrial fibrillation, atrial tachycardia, ventricular fibrillation, or ventricular tachyarrhythmia), sustained for at least 1 minute after administration of study intervention. Worsening arrhythmia events may or may not have been considered an AE, as determined by investigator judgment.
Time frame: Up to approximately 35 minutes post-administration
Population: All randomized participants who received at least one dose of study intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sugammadex 2 mg/kg | Percentage of Participants With Other Treatment-Emergent Cardiac Arrhythmia Events | 1.0 Percentage of participants |
| Sugammadex 4 mg/kg | Percentage of Participants With Other Treatment-Emergent Cardiac Arrhythmia Events | 0.0 Percentage of participants |
| Sugammadex 16 mg/kg | Percentage of Participants With Other Treatment-Emergent Cardiac Arrhythmia Events | 1.5 Percentage of participants |
| Neostigmine + Glycopyrrolate | Percentage of Participants With Other Treatment-Emergent Cardiac Arrhythmia Events | 2.0 Percentage of participants |
Comparison: Miettinen \& Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-valuep-value: 0.63795% CI: [-9.4, 4]Stratified Miettinen & Nurminen method
Comparison: Miettinen \& Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-valuep-value: 0.13495% CI: [-10.6, 1.5]Stratified Miettinen & Nurminen method
Comparison: Miettinen \& Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-valuep-value: 0.57795% CI: [-14.7, 5.8]Stratified Miettinen & Nurminen method
Primary
Percentage of Participants With Treatment-Emergent Sinus Bradycardia Events
The percentage of participants experiencing treatment-emergent sinus bradycardia events was identified with continuous electrocardiogram (ECG) monitoring. Treatment-emergent sinus bradycardia were 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 have been considered an adverse event (AE), as determined by investigator judgment.
Time frame: Up to approximately 35 minutes post-administration
Population: All randomized participants who received at least one dose of study intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sugammadex 2 mg/kg | Percentage of Participants With Treatment-Emergent Sinus Bradycardia Events | 1.0 Percentage of participants |
| Sugammadex 4 mg/kg | Percentage of Participants With Treatment-Emergent Sinus Bradycardia Events | 1.9 Percentage of participants |
| Sugammadex 16 mg/kg | Percentage of Participants With Treatment-Emergent Sinus Bradycardia Events | 7.4 Percentage of participants |
| Neostigmine + Glycopyrrolate | Percentage of Participants With Treatment-Emergent Sinus Bradycardia Events | 7.8 Percentage of participants |
Comparison: Miettinen \& Nurminen method stratified by neuromuscular blocking agent (NMBA) and American Society of Anesthesiologists (ASA) class was used to provide estimated between-treatment difference, 95% confidence interval, and p-valuep-value: 0.02695% CI: [-17.5, -0.8]Stratified Miettinen & Nurminen method
Comparison: Miettinen \& Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-valuep-value: 0.05895% CI: [-17.3, 0.2]Stratified Miettinen & Nurminen method
Comparison: Miettinen \& Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-valuep-value: 0.7395% CI: [-17.8, 8.6]Stratified Miettinen & Nurminen method
Primary
Percentage of Participants With Treatment-Emergent Sinus Tachycardia Events
The percentage of participants experiencing treatment-emergent sinus tachycardia events was 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 have been considered an AE, as determined by investigator judgment.
Time frame: Up to approximately 35 minutes post-administration
Population: All randomized participants who received at least one dose of study intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sugammadex 2 mg/kg | Percentage of Participants With Treatment-Emergent Sinus Tachycardia Events | 6.7 Percentage of participants |
| Sugammadex 4 mg/kg | Percentage of Participants With Treatment-Emergent Sinus Tachycardia Events | 9.3 Percentage of participants |
| Sugammadex 16 mg/kg | Percentage of Participants With Treatment-Emergent Sinus Tachycardia Events | 8.8 Percentage of participants |
| Neostigmine + Glycopyrrolate | Percentage of Participants With Treatment-Emergent Sinus Tachycardia Events | 21.6 Percentage of participants |
Comparison: Miettinen \& Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-valuep-value: 0.00795% CI: [-28.8, -4]Stratified Miettinen & Nurminen method
Comparison: Miettinen \& Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-valuep-value: 0.03695% CI: [-26.1, -0.8]Stratified Miettinen & Nurminen method
Comparison: Miettinen \& Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-valuep-value: 0.15895% CI: [-27.6, 3.6]Stratified Miettinen & Nurminen method