Neuromuscular Blockade
Conditions
Brief summary
A multi-center, randomized, parallel group, comparative, active controlled, safety assessor blinded trial in adult subjects comparing rocuronium plus sugammadex versus succinylcholine alone in subjects undergoing short surgical procedures in out-patient surgicenters. The primary objective was to evaluate changes in plasma potassium levels after treatment with rocuronium, sugammadex, or succinylcholine in adult subjects scheduled for short surgical procedures in out-patient surgicenters.
Interventions
DRUGrocuronium
A single bolus intubation dose of 0.6 mg/kg rocuronium will be administered following induction of anesthesia and if required, single bolus dose(s) of 0.15 mg/kg rocuronium will be administered to maintain the neuromuscular block.
DRUGsugammadex
At the end of the surgical procedure at a target depth of neuromuscular blockade of at least 1-2 Post-Tetanic Count (PTC), 4.0 mg/kg of sugammadex will be administered.
DRUGsuccinylcholine
A single bolus intubation dose of 1.0 mg/kg succinylcholine will be administered following induction of anesthesia and the subject is allowed to recover spontaneously from the neuromuscular blockade.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male or female subjects \>=18 years of age; * ASA Class 1-3; * Subjects with a Body Mass Index (BMI) of \< 35 kg/m\^2 ; * Subjects scheduled to undergo an elective short procedure with general anesthesia requiring neuromuscular relaxation and endotracheal intubation in outpatient surgicenters; * Subjects scheduled to undergo an elective surgical procedure expected to last 1.5 hours or less (from end of intubation to end of suturing/stapling of skin); * Subjects who are scheduled to undergo an elective surgical procedures that allows access to the arm for TOF-Watch® SX monitoring; * Subjects who have given written informed consent.
Exclusion criteria
* Subjects known to have ischemic heart disease or a history of myocardial infarction; * Subjects in whom a difficult intubation is expected because of anatomical malformations; * Subjects with medical conditions and/or undergoing surgical procedures that are not compatible with the use of the TOF-Watch SX (e.g., injuries to the thumbs/distal forearms, bilateral ulnar nerve damage or subjects with cardiac pacemakers); * Subjects known or suspected to have neuromuscular disorders impairing neuromuscular blockade (e.g., subjects with myasthenia gravis); * Subjects who would require the use of pneumatic tourniquet during the surgical procedure; * Subjects known or suspected to have significant renal dysfunction (e.g., creatinine clearance \< 30 mL per min); * Subjects known or suspected to have significant hepatic dysfunction; * Subjects known or suspected to have a (family) history of malignant hyperthermia; * Subjects known or suspected to be hypersensitive to sugammadex or other cyclodextrins or rocuronium or any of its excipients; * Subjects known or suspected to have an allergy to opiates/opioids, muscle relaxants, or other medications used during general anesthesia; * Subjects for whom a pre-established need for post operative intensive care admission and/or hospital admission is expected; * Subjects for whom an intra operative IV administration of fluids that contain potassium is expected; * Female subjects who are pregnant; * Female subjects who are breast-feeding; * Subjects who have participated in a previous sugammadex trial; * Subjects who have participated in another investigational drug trial within 30 days before entering into clinical trial (CT) 19.4.319 (P05700) unless pre-approved by the sponsor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plasma Potassium Levels at 5 Minutes After Treatment With Rocuronium or Succinylcholine | Baseline and 5 minutes post dose | Change from baseline = 5 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium or succinylcholine dose. Only data post rocuronium dose are included for rocuronium - sugammadex group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period). |
| Change From Baseline in Plasma Potassium Levels at 5 Minutes After Treatment With Sugammadex | Baseline and 5 minutes post dose | Change from baseline = 5 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium dose. Only data post sugammadex dose are included for rocuronium - sugammadex group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plasma Potassium Levels at 10 Minutes After Treatment With Rocuronium or Succinylcholine | Baseline and 10 minutes post dose | Change from baseline = 10 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium or succinylcholine dose. Only data post rocuronium dose are included for rocuronium - sugammadex group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period). |
| Change From Baseline in Plasma Potassium Levels at 10 Minutes After Treatment With Sugammadex | Baseline and 10 minutes post dose | Change from baseline = 10 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium dose. Only data post sugammadex dose are included for rocuronium - sugammadex group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period). |
| Change From Baseline in Plasma Potassium Levels at 15 Minutes After Treatment With Rocuronium or Succinylcholine | Baseline and 15 minutes post dose | Change from baseline = 15 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium or succinylcholine dose. Only data post rocuronium dose are included for rocuronium - sugammadex group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period). |
| Change From Baseline in Plasma Potassium Levels at 2 Minutes After Treatment With Rocuronium or Succinylcholine | Baseline and 2 minutes post dose | Change from baseline = 2 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium or succinylcholine dose. Only data post rocuronium dose are included for rocuronium - sugammadex group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period). |
| Number of Participants With at Least One Adverse Event (AE) in Rocuronium - Sugammadex and Succinylcholine Treatment Groups | Up to 7 days post dose | Only AEs which occurred following administration of sugammadex or succinylcholine are included. AEs in the rocuronium - sugammadex group occurring after rocuronium but before sugammadex administration are considered pretreatment events and are not included. The AE reporting interval included the entire intubation/surgical period for the succinylcholine group (since succinylcholine was administered just prior to intubation/commencement of surgery) but not for the rocuronium - sugammadex group (since sugammadex was administered at the end of the surgical procedure). |
| Time to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9 Following Administration of 4.0 mg/kg of Sugammadex After Neuromuscular Blockade Induced by Rocuronium | Start of administration of sugammadex to recovery from neuromuscular blockade (Up to approximately 6 minutes) | Neuromuscular functioning was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade, with a value of 1.0 representing full recovery. |
| Time to Recovery of T1 to 90% of Baseline Following Neuromuscular Blockade Induced by Succinylcholine | Start of administration of succinylcholine to recovery from neuromuscular blockade (Up to approximately 18 minutes) | Neuromuscular functioning was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. Nerve stimulation continued until recovery of T1 of 90% of baseline and full recovery of neuromuscular function occurred as determined by the anesthesiologist as per routine clinical practice. |
| Change From Baseline in Plasma Potassium Levels at 15 Minutes After Treatment With Sugammadex | Baseline and 15 minutes post dose | Change from baseline = 15 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium dose. Only data post sugammadex dose are included for rocuronium - sugammadex group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period). |
| Change From Baseline in Plasma Potassium Levels at 2 Minutes After Treatment With Sugammadex | Baseline and 2 minutes post dose | Change from baseline = 2 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium dose. Only data post sugammadex dose are included for rocuronium - sugammadex group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period). |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rocuronium - Sugammadex An intubation dose of rocuronium was administered following induction of anesthesia and, if required, maintenance doses were administered to maintain the neuromuscular block. At the end of the surgical procedure sugammadex was administered for reversal of neuromuscular blockade. | 66 |
| Succinylcholine An intubation dose of succinylcholine was administered following induction of anesthesia and the subject was allowed to recover spontaneously from the neuromuscular blockade. | 80 |
| Total | 146 |
Baseline characteristics
| Characteristic | Rocuronium - Sugammadex | Succinylcholine | Total |
|---|---|---|---|
| Age, Continuous | 40 years STANDARD_DEVIATION 13 | 45 years STANDARD_DEVIATION 14 | 43 years STANDARD_DEVIATION 14 |
| Sex: Female, Male Female | 48 Participants | 53 Participants | 101 Participants |
| Sex: Female, Male Male | 18 Participants | 27 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 57 / 66 | 67 / 80 |
| serious Total, serious adverse events | 1 / 66 | 3 / 80 |
Outcome results
Primary
Change From Baseline in Plasma Potassium Levels at 5 Minutes After Treatment With Rocuronium or Succinylcholine
Change from baseline = 5 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium or succinylcholine dose. Only data post rocuronium dose are included for rocuronium - sugammadex group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period).
Time frame: Baseline and 5 minutes post dose
Population: Participants who received rocuronium or succinylcholine with evaluable (i.e., not missing or hemolyzed) blood samples for potassium measurement at baseline and at the 5 minute post-dose time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rocuronium - Sugammadex | Change From Baseline in Plasma Potassium Levels at 5 Minutes After Treatment With Rocuronium or Succinylcholine | -0.06 mmol/L | Standard Deviation 0.32 |
| Succinylcholine | Change From Baseline in Plasma Potassium Levels at 5 Minutes After Treatment With Rocuronium or Succinylcholine | 0.30 mmol/L | Standard Deviation 0.34 |
Comparison: Treatment comparison was between the change from baseline in potassium level post-rocuronium dose versus post-succinylcholine dose, using a one way ANOVA model, with treatment as the term in the model.p-value: <0.0001ANOVA
Primary
Change From Baseline in Plasma Potassium Levels at 5 Minutes After Treatment With Sugammadex
Change from baseline = 5 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium dose. Only data post sugammadex dose are included for rocuronium - sugammadex group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period).
Time frame: Baseline and 5 minutes post dose
Population: Participants who received sugammadex with evaluable (i.e., not missing or hemolyzed) blood samples for potassium measurement at baseline and at the 5 minute post-dose time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rocuronium - Sugammadex | Change From Baseline in Plasma Potassium Levels at 5 Minutes After Treatment With Sugammadex | 0.02 mmol/L | Standard Deviation 0.42 |
Secondary
Change From Baseline in Plasma Potassium Levels at 10 Minutes After Treatment With Rocuronium or Succinylcholine
Change from baseline = 10 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium or succinylcholine dose. Only data post rocuronium dose are included for rocuronium - sugammadex group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period).
Time frame: Baseline and 10 minutes post dose
Population: Participants who received rocuronium or succinylcholine with evaluable (i.e., not missing or hemolyzed) blood samples for potassium measurement at baseline and at the 10 minute post-dose time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rocuronium - Sugammadex | Change From Baseline in Plasma Potassium Levels at 10 Minutes After Treatment With Rocuronium or Succinylcholine | -0.01 mmol/L | Standard Deviation 0.27 |
| Succinylcholine | Change From Baseline in Plasma Potassium Levels at 10 Minutes After Treatment With Rocuronium or Succinylcholine | 0.32 mmol/L | Standard Deviation 0.41 |
Comparison: Treatment comparison was between the change from baseline in potassium level post-rocuronium dose versus post-succinylcholine dose, using a one way ANOVA model, with treatment as the term in the model.p-value: <0.0001ANOVA
Secondary
Change From Baseline in Plasma Potassium Levels at 10 Minutes After Treatment With Sugammadex
Change from baseline = 10 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium dose. Only data post sugammadex dose are included for rocuronium - sugammadex group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period).
Time frame: Baseline and 10 minutes post dose
Population: Participants who received sugammadex with evaluable (i.e., not missing or hemolyzed) blood samples for potassium measurement at baseline and at the 10 minute post-dose time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rocuronium - Sugammadex | Change From Baseline in Plasma Potassium Levels at 10 Minutes After Treatment With Sugammadex | 0.07 mmol/L | Standard Deviation 0.38 |
Secondary
Change From Baseline in Plasma Potassium Levels at 15 Minutes After Treatment With Rocuronium or Succinylcholine
Change from baseline = 15 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium or succinylcholine dose. Only data post rocuronium dose are included for rocuronium - sugammadex group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period).
Time frame: Baseline and 15 minutes post dose
Population: Participants who received rocuronium or succinylcholine with evaluable (i.e., not missing or hemolyzed) blood samples for potassium measurement at baseline and at the 15 minute post-dose time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rocuronium - Sugammadex | Change From Baseline in Plasma Potassium Levels at 15 Minutes After Treatment With Rocuronium or Succinylcholine | 0.02 mmol/L | Standard Deviation 0.26 |
| Succinylcholine | Change From Baseline in Plasma Potassium Levels at 15 Minutes After Treatment With Rocuronium or Succinylcholine | 0.33 mmol/L | Standard Deviation 0.42 |
Comparison: Treatment comparison was between the change from baseline in potassium level post-rocuronium dose versus post-succinylcholine dose, using a one way ANOVA model, with treatment as the term in the model.p-value: <0.0001ANOVA
Secondary
Change From Baseline in Plasma Potassium Levels at 15 Minutes After Treatment With Sugammadex
Change from baseline = 15 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium dose. Only data post sugammadex dose are included for rocuronium - sugammadex group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period).
Time frame: Baseline and 15 minutes post dose
Population: Participants who received sugammadex with evaluable (i.e., not missing or hemolyzed) blood samples for potassium measurement at baseline and at the 15 minute post-dose time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rocuronium - Sugammadex | Change From Baseline in Plasma Potassium Levels at 15 Minutes After Treatment With Sugammadex | 0.07 mmol/L | Standard Deviation 0.39 |
Secondary
Change From Baseline in Plasma Potassium Levels at 2 Minutes After Treatment With Rocuronium or Succinylcholine
Change from baseline = 2 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium or succinylcholine dose. Only data post rocuronium dose are included for rocuronium - sugammadex group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period).
Time frame: Baseline and 2 minutes post dose
Population: Participants who received rocuronium or succinylcholine with evaluable (i.e., not missing or hemolyzed) blood samples for potassium measurement at baseline and at the 2 minute post-dose time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rocuronium - Sugammadex | Change From Baseline in Plasma Potassium Levels at 2 Minutes After Treatment With Rocuronium or Succinylcholine | -0.09 mmol/L | Standard Deviation 0.3 |
| Succinylcholine | Change From Baseline in Plasma Potassium Levels at 2 Minutes After Treatment With Rocuronium or Succinylcholine | 0.19 mmol/L | Standard Deviation 0.36 |
Comparison: Treatment comparison was between the change from baseline in potassium level post-rocuronium dose versus post-succinylcholine dose, using a one way ANOVA model, with treatment as the term in the model.p-value: <0.0001ANOVA
Secondary
Change From Baseline in Plasma Potassium Levels at 2 Minutes After Treatment With Sugammadex
Change from baseline = 2 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium dose. Only data post sugammadex dose are included for rocuronium - sugammadex group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period).
Time frame: Baseline and 2 minutes post dose
Population: Participants who received sugammadex with evaluable (i.e., not missing or hemolyzed) blood samples for potassium measurement at baseline and at the 2 minute post-dose time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rocuronium - Sugammadex | Change From Baseline in Plasma Potassium Levels at 2 Minutes After Treatment With Sugammadex | -0.02 mmol/L | Standard Deviation 0.39 |
Secondary
Number of Participants With at Least One Adverse Event (AE) in Rocuronium - Sugammadex and Succinylcholine Treatment Groups
Only AEs which occurred following administration of sugammadex or succinylcholine are included. AEs in the rocuronium - sugammadex group occurring after rocuronium but before sugammadex administration are considered pretreatment events and are not included. The AE reporting interval included the entire intubation/surgical period for the succinylcholine group (since succinylcholine was administered just prior to intubation/commencement of surgery) but not for the rocuronium - sugammadex group (since sugammadex was administered at the end of the surgical procedure).
Time frame: Up to 7 days post dose
Population: Participants who received sugammadex or succinylcholine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rocuronium - Sugammadex | Number of Participants With at Least One Adverse Event (AE) in Rocuronium - Sugammadex and Succinylcholine Treatment Groups | 60 participants |
| Succinylcholine | Number of Participants With at Least One Adverse Event (AE) in Rocuronium - Sugammadex and Succinylcholine Treatment Groups | 75 participants |
Secondary
Time to Recovery of T1 to 90% of Baseline Following Neuromuscular Blockade Induced by Succinylcholine
Neuromuscular functioning was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. Nerve stimulation continued until recovery of T1 of 90% of baseline and full recovery of neuromuscular function occurred as determined by the anesthesiologist as per routine clinical practice.
Time frame: Start of administration of succinylcholine to recovery from neuromuscular blockade (Up to approximately 18 minutes)
Population: Participants who received succinylcholine and had evaluable neuromuscular function data determined to be reliable by a central independent adjudication committee.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Rocuronium - Sugammadex | Time to Recovery of T1 to 90% of Baseline Following Neuromuscular Blockade Induced by Succinylcholine | 10.76 Minutes |
Secondary
Time to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9 Following Administration of 4.0 mg/kg of Sugammadex After Neuromuscular Blockade Induced by Rocuronium
Neuromuscular functioning was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade, with a value of 1.0 representing full recovery.
Time frame: Start of administration of sugammadex to recovery from neuromuscular blockade (Up to approximately 6 minutes)
Population: Participants who received both rocuronium and sugammadex and had evaluable neuromuscular function data determined to be reliable by a central independent adjudication committee.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Rocuronium - Sugammadex | Time to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9 Following Administration of 4.0 mg/kg of Sugammadex After Neuromuscular Blockade Induced by Rocuronium | 1.79 Minutes |