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The investigators propose a randomized trial comparing sugammadex and neostigmine for the reversal of neuromuscular blocks induced by rocuronium or vecuronium in adults having general anesthesia with muscular block for noncardiac surgery.
All patients will be asked to void before they are transferred to the operating room. Patients will be seen shortly before anesthetic induction (baseline, Visit 1). As this is a pragmatic trial, no restrictions to anesthetic management other than the random allocation to sugammadex or neostigmine are planned.
As part of local standards, it is recommended to maintain a moderate block of 1 to 2 twitch responses to train-of-four (TOF) stimulation throughout surgery.
Randomized treatments will be implemented by clinicians in collaboration with research personnel. Patients will be randomized shortly before the reversal of the neuromuscular block. At the time of randomization, the administration of either neostigmine or sugammadex need to be possible. If e.g. the neuromuscular block is too deep to be reversed with neostigmine, patients will not be randomized and excluded from the study.
The anesthesiologist in charge will be informed on the patient's allocation to either the sugammadex or neostigmine group by an unblinded investigator. Patients will be monitored for twitch responses towards the end of surgery to determine the timing and dose for the reversal agent. The twitch response will be measured using a quantitative, acceleromyographic monitoring device. For sugammadex, 4 mg/kg is recommended if spontaneous recovery of the twitch response has reached 1 to 2 post-tetanic counts (PTC) and there are no twitch responses to (TOF) stimulation. Alternatively, 2 mg/kg is recommended if spontaneous recovery has reached the reappearance of the second twitch in response to TOF stimulation. In the neostigmine group, neostigmine 2.5 mg with glycopyrrolate 0.5 mg will be administered as an initial dose. Neostigmine and glycopyrrolate are to be administered in a fixed ratio, and only if the second twitch in response to TOF stimulation has appeared. The initial dose can be repeated up to a ceiling dose of 5 mg neostigmine with 1 mg of glycopyrrolate. However, the final decision of the dose will be up to the attending anesthesiologist. The administered dose will be recorded. All patients are required to have a documented TOF ratio > 0.9 before extubation Visit 2 is one hour after surgery in the post anesthesia care unit (PACU). The third Visit is within 4 to 6 hours after surgery on the regular ward. Visit 4 and 5 will be in the morning and afternoon of the first day after surgery (postoperative day (POD) 1). Visit 5 on the afternoon of POD 1 will be the last follow-up and the end of a patient's participation in the study. Thereafter, data will be recorded from electronical medical records until POD 4 or discharge, whichever comes first.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Neostigmine | Active Comparator | Reversal of Neuromuscular Block by Neostigmine. |
|
| Sugammadex | Active Comparator | Reversal of Neuromuscular Block by Sugammadex. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Neostigmine with glycopyrrolate | Drug | Administration by intravenous infusion |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Urine Residual in PACU | The primary outcome of urinary retention is assessed by post-void bladder volume. | 1 hour after surgery, which started from out of operation room |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Needed a Urinary Catheter | participants who needed a urinary catheter within 24 hours after surgery | within 24 hours after out of operation room |
| Measure | Description | Time Frame |
|---|---|---|
| Participants Having Urinary Tract Infections | patients having urinary tract infections during the hospitalization | during postoperative hospital stay, which from out of operation room to discharge from the hospital, an average of 1 week |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kurt Ruetzler, MD | The Cleveland Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Neostigmine | Reversal of Neuromuscular Block by Neostigmine. Neostigmine with glycopyrrolate: Administration by intravenous infusion |
| FG001 | Sugammadex | Reversal of Neuromuscular Block by Sugammadex. Sugammadex: Administration by intravenous infusion |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Neostigmine | Reversal of Neuromuscular Block by Neostigmine. Neostigmine with glycopyrrolate: Administration by intravenous infusion |
| BG001 | Sugammadex | Reversal of Neuromuscular Block by Sugammadex. Sugammadex: Administration by intravenous infusion |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Urine Residual in PACU | The primary outcome of urinary retention is assessed by post-void bladder volume. | A total of 50 patients were included in data analysis based on the modified intent-to-treat rule | Posted | Median | Inter-Quartile Range | ml | 1 hour after surgery, which started from out of operation room |
|
The time frame for AE is during the entire duration of the study, which from the participant signs the informed consent through participant discharged from the hospital after the surgery, up to 7 days.
A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose: is life-threatening; or requires inpatient hospitalization or prolongation of existing hospitalization; or results in persistent or significant disability/incapacity; or is a congenital anomaly/birth defect; or is a medically important event.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Neostigmine | Reversal of Neuromuscular Block by Neostigmine. Neostigmine with glycopyrrolate: Administration by intravenous infusion |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kurt Ruetzler, MD | Cleveland Clinic Foundation | 216 636-0561 | RUETZLK@ccf.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 1, 2022 | Oct 15, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009388 | Neostigmine |
| D006024 | Glycopyrrolate |
| D000077122 | Sugammadex |
| ID | Term |
|---|---|
| D050338 | Phenylammonium Compounds |
| D000644 | Quaternary Ammonium Compounds |
| D000588 | Amines |
| D009930 | Organic Chemicals |
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| Sugammadex |
| Drug |
Administration by intravenous infusion |
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| ASA score | The ASA score refers to the American Society of Anesthesiologists (ASA) Physical Status Classification System, which is used to assess the preoperative physical health of a patient before surgery. ASA score and measure description: I: A normal, healthy patient. II: A patient with mild systemic disease. III: A patient with severe systemic disease. IV: A patient with severe systemic disease that is a constant threat to life. V: A moribund patient who is not expected to survive without the operation. VI: A declared brain-dead patient whose organs are being removed for donor purposes. | Count of Participants | Participants |
|
| BMI | Median | Inter-Quartile Range | kg/m2 |
|
| pulmonary disease | Count of Participants | Participants |
|
| cardiac disease | Count of Participants | Participants |
|
| kidney disease | Count of Participants | Participants |
|
| neurological disease | Count of Participants | Participants |
|
| previous surgery | Count of Participants | Participants |
|
| Metabolic equivalent | Metabolic Equivalent (MET) is a unit used to estimate the energy cost of physical activities, expressed as multiples of the resting metabolic rate (RMR). It provides a standardized way to measure and compare the intensity of various physical activities.1 MET = The energy expenditure of an individual at rest. MET Categories:
Running, swimming, or aerobic exercise. | Count of Participants | Participants |
|
| Substance abuse-illegal drug use | Count of Participants | Participants |
|
| Substance abuse -alcohol abuse | Count of Participants | Participants |
|
|
|
| Secondary | Number of Participants Who Needed a Urinary Catheter | participants who needed a urinary catheter within 24 hours after surgery | Posted | Count of Participants | Participants | within 24 hours after out of operation room |
|
|
|
| Other Pre-specified | Participants Having Urinary Tract Infections | patients having urinary tract infections during the hospitalization | Posted | Count of Participants | Participants | during postoperative hospital stay, which from out of operation room to discharge from the hospital, an average of 1 week |
|
|
|
| 0 |
| 23 |
| 0 |
| 23 |
| 0 |
| 23 |
| EG001 | Sugammadex | Reversal of Neuromuscular Block by Sugammadex. Sugammadex: Administration by intravenous infusion | 0 | 27 | 0 | 27 | 0 | 27 |
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| D009861 |
| Onium Compounds |
| D011759 | Pyrrolidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D047408 | gamma-Cyclodextrins |
| D003505 | Cyclodextrins |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D003912 | Dextrins |
| D013213 | Starch |
| D005936 | Glucans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |