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| ID | Type | Description | Link |
|---|---|---|---|
| MISP #60224 | Other Grant/Funding Number | Merck & Co., INC. |
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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Colon and rectal surgery is associated with high cost, long length of stay, high postoperative surgical site infection rate, high incidence of postoperative nausea and vomiting, and a high rate of hospital readmission. Return of bowel function is of utmost importance in avoiding patient discomfort, morbidity, and mortality after colorectal surgery. All patient having colorectal surgery receive neuromuscular paralysis, which is reversed at the end of surgery with either glycopyrrolate and neostigmine, or sugammadex. Glycopyrrolate and neostigmine both affect bowel function. Sugammadex has no effect on bowel function. The purpose of this study is to determine if a strategy of neuromuscular reversal with sugammadex, instead of glycopyrrolate and neostigmine, may increase gastric emptying after surgery and lead to less postoperative complications.
Colon and rectal surgery is associated with high cost, long length of stay, high postoperative surgical site infection rate, high incidence of postoperative nausea and vomiting, and a high rate of hospital readmission. The 30-day mortality rate after open or laparoscopic surgery for colorectal cancer is high-between 3 and 8%. Return of bowel function is of utmost importance in avoiding patient discomfort, morbidity, and mortality after colorectal surgery. The incidence of postoperative ileus after colorectal surgery has been reported to be 10-25%. Postoperative ileus is defined as intolerance of oral intake due to a lack of coordinated bowel motility. Significant attention has been paid to the development of guidelines and programs to reduce the incidence of postoperative ileus and accelerate return of bowel function after colorectal surgery.
The American Society of Colon and Rectal Surgeons (ASCRS) and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) created an enhanced recovery after surgery (ERAS) protocol to promote the following outcomes in patients undergoing colorectal surgery: "freedom from nausea, freedom from pain at rest, early return of bowel function, improved wound healing, and early hospital discharge". An intervention that facilitates faster postoperative gastric emptying may impact many of these outcomes; in particular, nausea may be reduced, constipation-associated pain at rest may decline, return of bowel function would be accelerated, and time to hospital discharge may be shortened. While administration of medications such as Alvimopan and adjustments in anesthetic technique (providing epidural analgesia, minimizing crystalloid administration, using multimodal analgesia) are recommended, sugammadex is not currently considered in the ERAS protocol.
Neuromuscular paralysis is required for the duration of open and laparoscopic colorectal surgery to decrease patient movement, improve operating conditions, and at times facilitate ventilation. Neostigmine and glycopyrrolate are commonly used to reverse rocuronium neuromuscular blockade at the end of surgery. Both neostigmine and glycopyrrolate impact bowel function. Neostigmine promotes and glycopyrrolate slows gastrointestinal motility. Co-administration of neostigmine and glycopyrrolate can have variable effects on return of bowel function after surgery. In general, administering a higher proportion of neostigmine than glycopyrrolate is associated with faster return of bowel function. Unopposed cholinergic activity from neostigmine administration can cause morbidity including bradycardia, bronchoconstriction, hypotension, urinary incontinence, and increased salivary secretions. Thus, the ratio of neostigmine to glycopyrrolate is relatively fixed and cannot be adjusted to promote desired gastrointestinal outcomes. Sugammadex does not bind to acetylcholine receptors on bowel and is presumed not to affect bowel function.
Some investigations into the contribution of sugammadex versus acetylcholinesterase inhibitors to recovery of bowel function have been completed. In retrospective studies, sugammadex administration has been associated with faster time to first bowel movement and less ileus-related delays in hospital discharge. Conversely, two randomized, controlled clinical trials found no difference in outcomes related to gastrointestinal motility including time to first flatus, time to first bowel movement, and incidence of postoperative ileus. One randomized, controlled trial found a shorter time to first flatus, but no difference in time to first bowel movement. Lastly, one study found a trend towards faster gastric emptying with sugammadex. A limitation of the aforementioned prospective studies is they include patients having surgery on their thyroid gland, gallbladder, and other intraabdominal organs. These surgeries lack bowel handling and anastomosis, which translates to less effect on postoperative bowel function. It is hypothesized that a randomized, controlled trial involving patients having colorectal surgery will find faster gastric emptying, less nausea, and less gastrointestinal complications (including ileus) when sugammadex is administered to reverse rocuronium neuromuscular blockade, compared to neostigmine.
The purpose of this study is to determine if administering sugammadex for reversal of neuromuscular blockade instead of neostigmine and glycopyrrolate, a strategy that avoids cholinergic effects on the bowel, is associated with faster gastric emptying, faster time to achieve a TOFr > 0.9, less post-surgical gastrointestinal complications, shorter time to first bowel movement, shorter PACU phase 1 recovery, and shorter hospital length of stay. If sugammadex is shown to improve the aforementioned outcomes, an argument can be made that sugammadex should be considered for inclusion in the ERAS protocol for Colorectal surgery.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sugammadex | Experimental | Sugammadex 2 mg/kg IV once at the end of surgery |
|
| Neostigmine | Active Comparator | Neostigmine 0.07 mg/kg to a maximum of 5 mg (+Glycopyrrolate 0.2 mg per 1 mg of neostigmine administered) IV once at the end of surgery |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sugammadex | Drug | At the end of the surgical procedure at a depth of neuromuscular blockade after the reappearance of T2 on the train-of-four, Sugammadex will be dosed once at 2 mg/kg actual body weight through an intravenous line with brisk flow |
| Measure | Description | Time Frame |
|---|---|---|
| Gastric Emptying | Gastric emptying as assessed by the area under the paracetamol concentration-time curve by trapezoidal approximation (AUC) | 150 minutes after neuromuscular reversal |
| Measure | Description | Time Frame |
|---|---|---|
| Time in Minutes to Reach Train of Four (TOF) Ratio ≥ 0.9 After the Administration of Reversal Drug. | The TOF ratio will be measured in continuous manner every 15 seconds after the administration of reversal drug. The TOF ratio will be measured by the TwitchView electromyograph. The TOF ratio was measured in this study by stimulating the ulnar nerve with four equal stimuli at a frequency of 2 hertz. The TOF ratio is calculated by dividing the amplitude of the muscle response from the fourth stimuli by the amplitude of the muscle response from the first stimuli. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Brandon M Togioka, MD | Oregon Health and Science University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Oregon Health & Science University | Portland | Oregon | 97239 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40327558 | Derived | Togioka BM, Rakshe SK, Ye S, Tekkali P, Tsikitis VL, Fang SH, Herzig DO, Lu KC, Aziz MF. A Randomized Controlled Trial of Sugammadex versus Neostigmine for Reversal of Rocuronium on Gastric Emptying in Adults Undergoing Elective Colorectal Surgery. Anesth Analg. 2025 Aug 1;141(2):373-383. doi: 10.1213/ANE.0000000000007518. Epub 2025 May 6. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Sugammadex | Sugammadex 2 mg/kg IV once at the end of surgery Sugammadex: At the end of the surgical procedure at a depth of neuromuscular blockade after the reappearance of T2 on the train-of-four, Sugammadex will be dosed once at 2 mg/kg actual body weight through an intravenous line with brisk flow |
| FG001 | Neostigmine | Neostigmine 0.07 mg/kg to a maximum of 5 mg (+Glycopyrrolate 0.2 mg per 1 mg of neostigmine administered) IV once at the end of surgery Neostigmine: At the end of surgical procedure at a depth of neuromuscular blockade after the reappearance of T2 on the train-of-four, Neostigmine will be dosed once at 0.07 mg/kg actual body weight to a maximum of 5 mg through an intravenous line with brisk flow. Glycopyrrolate will be coadministered with Neostigmine at a dose of 0.2 mg of Glycopyrrolate per 1.0 mg of Neostigmine administered |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Sugammadex | Sugammadex 2 mg/kg IV once at the end of surgery Sugammadex: At the end of the surgical procedure at a depth of neuromuscular blockade after the reappearance of T2 on the train-of-four, Sugammadex will be dosed once at 2 mg/kg actual body weight through an intravenous line with brisk flow |
| BG001 |
| 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 | Gastric Emptying | Gastric emptying as assessed by the area under the paracetamol concentration-time curve by trapezoidal approximation (AUC) | Posted | Mean | Standard Deviation | log(ng*ml-1)*min | 150 minutes after neuromuscular reversal |
|
30 days
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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 | Sugammadex | Sugammadex 2 mg/kg IV once at the end of surgery Sugammadex: At the end of the surgical procedure at a depth of neuromuscular blockade after the reappearance of T2 on the train-of-four, Sugammadex will be dosed once at 2 mg/kg actual body weight through an intravenous line with brisk flow |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypersensitivity Reaction | Immune system disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| nausea or vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Brandon Togioka | Oregon Health & Science University | 503-494-4572 | togioka@ohsu.edu |
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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 | Jul 23, 2020 | Jun 18, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D007410 | Intestinal Diseases |
| D011183 | Postoperative Complications |
| ID | Term |
|---|---|
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000077122 | Sugammadex |
| D009388 | Neostigmine |
| ID | Term |
|---|---|
| D047408 | gamma-Cyclodextrins |
| D003505 | Cyclodextrins |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
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Assessor-blinded, randomized, controlled, single center, parallel design trial with patient masking
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|
| Neostigmine | Drug | At the end of surgical procedure at a depth of neuromuscular blockade after the reappearance of T2 on the train-of-four, Neostigmine will be dosed once at 0.07 mg/kg actual body weight to a maximum of 5 mg through an intravenous line with brisk flow. Glycopyrrolate will be coadministered with Neostigmine at a dose of 0.2 mg of Glycopyrrolate per 1.0 mg of Neostigmine administered |
|
|
| 30 minutes after the administration of reversal drug. |
| Number of Participants With Gastrointestinal Complications | Gastrointestinal complications will include all of the following: anastomotic leak, postoperative ileus, reoperation, and organ space infection. National Surgical Quality Improvement Project definitions will be used. Active monitoring for these outcomes will occur on an ongoing daily basis until hospital discharge. In addition, chart review and patient phone call will occur 30 days after discharge to assess for complications after discharge. | 30 days after surgery |
| PACU Recovery Time | The time to attain pain control and stable respiratory, hemodynamic, and neurologic status after surgery. | 1 day |
| Reversal Time to First Bowel Movement | The time from reversal of neuromuscular blockade to first bowel movement | length hospitalization, an average of 1 week |
| Reversal Time to Discharge Order | The number of days between reversal of neuromuscular blockade and time of discharge order | length of hospitalization, an average of 1 week |
| Neostigmine |
Neostigmine 0.07 mg/kg to a maximum of 5 mg (+Glycopyrrolate 0.2 mg per 1 mg of neostigmine administered) IV once at the end of surgery Neostigmine: At the end of surgical procedure at a depth of neuromuscular blockade after the reappearance of T2 on the train-of-four, Neostigmine will be dosed once at 0.07 mg/kg actual body weight to a maximum of 5 mg through an intravenous line with brisk flow. Glycopyrrolate will be coadministered with Neostigmine at a dose of 0.2 mg of Glycopyrrolate per 1.0 mg of Neostigmine administered |
| 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 |
|
| Region of Enrollment | Number | participants |
|
| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
|
| ASA Physical Status | Count of Participants | Participants |
|
|
|
|
| Secondary | Time in Minutes to Reach Train of Four (TOF) Ratio ≥ 0.9 After the Administration of Reversal Drug. | The TOF ratio will be measured in continuous manner every 15 seconds after the administration of reversal drug. The TOF ratio will be measured by the TwitchView electromyograph. The TOF ratio was measured in this study by stimulating the ulnar nerve with four equal stimuli at a frequency of 2 hertz. The TOF ratio is calculated by dividing the amplitude of the muscle response from the fourth stimuli by the amplitude of the muscle response from the first stimuli. | Posted | Mean | Standard Deviation | minutes | 30 minutes after the administration of reversal drug. |
|
|
|
|
| Secondary | Number of Participants With Gastrointestinal Complications | Gastrointestinal complications will include all of the following: anastomotic leak, postoperative ileus, reoperation, and organ space infection. National Surgical Quality Improvement Project definitions will be used. Active monitoring for these outcomes will occur on an ongoing daily basis until hospital discharge. In addition, chart review and patient phone call will occur 30 days after discharge to assess for complications after discharge. | Posted | Count of Participants | Participants | 30 days after surgery |
|
|
|
|
| Secondary | PACU Recovery Time | The time to attain pain control and stable respiratory, hemodynamic, and neurologic status after surgery. | Posted | Mean | Standard Deviation | minutes | 1 day |
|
|
|
|
| Secondary | Reversal Time to First Bowel Movement | The time from reversal of neuromuscular blockade to first bowel movement | Posted | Mean | Standard Deviation | hours | length hospitalization, an average of 1 week |
|
|
|
|
| Secondary | Reversal Time to Discharge Order | The number of days between reversal of neuromuscular blockade and time of discharge order | Posted | Mean | Standard Deviation | days | length of hospitalization, an average of 1 week |
|
|
|
|
| 0 |
| 60 |
| 2 |
| 60 |
| 10 |
| 60 |
| EG001 | Neostigmine | Neostigmine 0.07 mg/kg to a maximum of 5 mg (+Glycopyrrolate 0.2 mg per 1 mg of neostigmine administered) IV once at the end of surgery Neostigmine: At the end of surgical procedure at a depth of neuromuscular blockade after the reappearance of T2 on the train-of-four, Neostigmine will be dosed once at 0.07 mg/kg actual body weight to a maximum of 5 mg through an intravenous line with brisk flow. Glycopyrrolate will be coadministered with Neostigmine at a dose of 0.2 mg of Glycopyrrolate per 1.0 mg of Neostigmine administered | 0 | 60 | 5 | 60 | 13 | 60 |
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Upper Airway Obstruction | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Foul, salty, or metallic taste | Nervous system disorders | Systematic Assessment |
|
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| D003912 |
| Dextrins |
| D013213 | Starch |
| D005936 | Glucans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
| D050338 | Phenylammonium Compounds |
| D000644 | Quaternary Ammonium Compounds |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D009861 | Onium Compounds |