- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05661409
Sugammadex as Rescue Therapy
The Use of Sugammadex as Rescue Therapy Following Inadequate Reversal With Neostigmine
Neuromuscular blocking agents (NMBAs) are commonly used in the practice of anesthesiology for skeletal muscle relaxation to facilitate tracheal intubation, mechanical ventilation, and to provide optimal surgical conditions. In order to prevent residual NMB, it is vital to adequately reverse any use of a non-depolarizing NMBA. This was historically done using an anticholinesterase such as neostigmine, which would increase the concentration of acetylcholine at the neuromuscular junction leading to the return of neuromuscular transmission. Unfortunately, there are disadvantages to the use of an anticholinesterase. It was in this context that sugammadex was found to be a valuable addition to the anesthesiologist's armamentarium. It is a modified γ-cyclodextrin that encapsulates the aminosteroid NMBAs rocuronium and vecuronium.
This project is a double-blind randomized placebo-controlled dose-response trial that aims to determine the time taken to achieve adequate reversal comparing five doses of sugammadex as rescue therapy following inadequate reversal with neostigmine. The study team will recruit patients aged 18 years and above from the main operating room and outpatient surgery center at Grady Memorial Hospital who are undergoing elective surgery under general anesthesia, who has received NMB, received neostigmine for NMB reversal, and achieved a TOF count ≥ 3 twitches but not a TOF ratio of 0.9 fifteen minutes after neostigmine was given. Those with a TOF count < 3 twitches will drop out of the study as there are already specified doses of sugammadex for that level of NMB
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Neuromuscular blocking (NMB) agents are commonly used in the practice of anesthesiology for skeletal muscle relaxation to facilitate tracheal intubation, and may require reversal in order to prevent residual NMB. This was historically done using an anticholinesterase such as neostigmine, which has many adverse effects and may not effectively reverse a deep NMB. However, the introduction of sugammadex was instrumental in allowing the rapid return of neuromuscular function. The FDA has only approved three doses of sugammadex (2 mg/kg, 4 mg/kg and 16 mg/kg) depending on the train of four (TOF) count, which is a qualitative measure of the depth of NMB and ranges from 0 to 4 twitches. Conversely, the TOF ratio is a quantitative measure, is calculated using the ratio of the amplitude of the fourth twitch to the first twitch, and ranges from 0 to 1. A TOF ratio of 0.9 is generally accepted as the minimum threshold to safely extubate a patient, but this information is not always readily accessible as many anesthesia providers do not have a quantitative NMB monitor.
In 2020, Carvalho et al. conducted a meta-analysis of 53 studies (12,664 adult patients) where the pooled residual NMB incidence ranged from 0.115 when quantitative neuromuscular monitoring was used to 0.331 where no neuromuscular monitoring was used. Ravel et al. conducted a meta-analysis of 20 randomized controlled trials (1,923 adult patients), where residual NMB was found in 2.8% of patients who received sugammadex compared to 39% of those who received neostigmine 15 minutes post administration. Concerningly, 60 minutes after administration, 2.1% of the sugammadex group versus 19% of the neostigmine group still had NMB. When expanded to observational studies (58 studies with 25,277 adult patients), the incidence of residual NMB ranged from 0% to 90.5% (median 30%), which was significantly lower (0% to 16%) in the sugammadex group compared to 3.5% to 90.5% in the neostigmine group and 15% to 89% in the spontaneous recovery group.
This project is a double-blind randomized placebo-controlled dose-response trial that aims to determine the time taken to achieve adequate reversal comparing five doses of sugammadex as rescue therapy following inadequate reversal with neostigmine. The study team will recruit patients aged 18 years and above from the main operating room and outpatient surgery center at Grady Memorial Hospital who are undergoing elective surgery under general anesthesia, who has received NMB, received neostigmine for NMB reversal, and achieved a TOF count ≥ 3 twitches but not a TOF ratio of 0.9 fifteen minutes after neostigmine was given. Those with a TOF count < 3 twitches will drop out of the study as there are already specified doses of sugammadex for that level of NMB.
These patients will then be randomized to six groups: 2 mg/kg (the lowest dose approved by the FDA), 1 mg/kg, 0.5 mg/kg, 0.25 mg/kg, 0.125 mg/kg of sugammadex, and placebo. The time taken to reach a TOF ratio of 0.9 thereafter would be measured and compared for statistically significant differences.
Study Type
Enrollment (Estimated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Rebecca Wong, M.B.B.S.
- Phone Number: 443-683-9968
- Email: rebecca.yuen.shi.wong@emory.edu
Study Locations
-
-
Georgia
-
Atlanta, Georgia, United States, 30303
- Recruiting
- Grady Memorial Hospital
-
Contact:
- Rebecca Wong, M.B.B.S.
- Phone Number: 443-683-9968
- Email: rebecca.yuen.shi.wong@emory.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Patients aged 18 years and above who will
- Undergo an elective surgery in the main operating room or outpatient surgery center at Grady Memorial Hospital,
- Receive general anesthesia (standardized to sevoflurane for maintenance),
- Receive rocuronium for NMB,
- Receive neostigmine for NMB reversal,
- Achieve a TOF count of at least 3 twitches but not a TOF ratio of 0.9 fifteen minutes after neostigmine has been given, and
- Able and willing to provide informed consent.
Exclusion Criteria:
- Pregnancy and/or lactating
- BMI ≥ 40,
- Severe renal impairment, i.e. chronic kidney disease stages IV and V as defined by GFR < 30 ml/min/1.73 m2
- Severe hepatic impairment, i.e. Child-Pugh score C
- Pre-existing neuromuscular disease,
- Anticipated need for postoperative intubation, and/or
- Known hypersensitivity reactions to rocuronium, neostigmine and/or sugammadex.
- Adults unable to consent
- Prisoners
- Cognitively impaired or Individuals with Impaired Decision-Making Capacity
- Individuals who are not able to clearly understand English
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Sugammadex 2 mg/kg
The study team will identify patients who are scheduled to undergo an elective surgery under general anesthesia, received rocuronium for NMB and neostigmine for NMB reversal. Patients will be randomized using the Emory University REDCap (Research Electronic Data Capture) software to six groups: 2 mg/kg (the lowest dose approved by the FDA), 1 mg/kg, 0.5 mg/kg, 0.25 mg/kg, 0.125 mg/kg of sugammadex and placebo. Doses would be based on actual body weight. The time taken to reach a TOF ratio of 0.9 thereafter would be measured. If the patient fails to achieve this goal by 10 minutes, sugammadex would be given in 2 mg/kg increments until the patient reaches this threshold and can be safely extubated. The TOF ratio would be measured again at 30 minutes after arrival at the PACU to exclude delayed residual NMB with the plan to give further 2 mg/kg doses of sugammadex if detected. |
Sugammadex is a FDA-approved drug that is in routine clinical use for NMB reversal. Patients will be randomized to six groups: 2 mg/kg (the lowest dose approved by the FDA), 1 mg/kg, 0.5 mg/kg, 0.25 mg/kg, 0.125 mg/kg of sugammadex and placebo. Doses would be based on actual body weight. The time taken to reach a TOF ratio of 0.9 thereafter would be measured. If the patient fails to achieve this goal by 10 minutes, sugammadex would be given in 2 mg/kg increments until the patient reaches this threshold and can be safely extubated. |
Experimental: Sugammadex 1 mg/kg
The study team will identify patients who are scheduled to undergo an elective surgery under general anesthesia, received rocuronium for NMB and neostigmine for NMB reversal. Patients will be randomized using the Emory University REDCap (Research Electronic Data Capture) software to six groups: 2 mg/kg (the lowest dose approved by the FDA), 1 mg/kg, 0.5 mg/kg, 0.25 mg/kg, 0.125 mg/kg of sugammadex and placebo. Doses would be based on actual body weight. The time taken to reach a TOF ratio of 0.9 thereafter would be measured. If the patient fails to achieve this goal by 10 minutes, sugammadex would be given in 2 mg/kg increments until the patient reaches this threshold and can be safely extubated. The TOF ratio would be measured again at 30 minutes after arrival at the PACU to exclude delayed residual NMB with the plan to give further 2 mg/kg doses of sugammadex if detected. |
Sugammadex is a FDA-approved drug that is in routine clinical use for NMB reversal. Patients will be randomized to six groups: 2 mg/kg (the lowest dose approved by the FDA), 1 mg/kg, 0.5 mg/kg, 0.25 mg/kg, 0.125 mg/kg of sugammadex and placebo. Doses would be based on actual body weight. The time taken to reach a TOF ratio of 0.9 thereafter would be measured. If the patient fails to achieve this goal by 10 minutes, sugammadex would be given in 2 mg/kg increments until the patient reaches this threshold and can be safely extubated. |
Experimental: Sugammadex 0.5 mg/kg
The study team will identify patients who are scheduled to undergo an elective surgery under general anesthesia, received rocuronium for NMB and neostigmine for NMB reversal. Patients will be randomized using the Emory University REDCap (Research Electronic Data Capture) software to six groups: 2 mg/kg (the lowest dose approved by the FDA), 1 mg/kg, 0.5 mg/kg, 0.25 mg/kg, 0.125 mg/kg of sugammadex and placebo. Doses would be based on actual body weight. The time taken to reach a TOF ratio of 0.9 thereafter would be measured. If the patient fails to achieve this goal by 10 minutes, sugammadex would be given in 2 mg/kg increments until the patient reaches this threshold and can be safely extubated. The TOF ratio would be measured again at 30 minutes after arrival at the PACU to exclude delayed residual NMB with the plan to give further 2 mg/kg doses of sugammadex if detected. |
Sugammadex is a FDA-approved drug that is in routine clinical use for NMB reversal. Patients will be randomized to six groups: 2 mg/kg (the lowest dose approved by the FDA), 1 mg/kg, 0.5 mg/kg, 0.25 mg/kg, 0.125 mg/kg of sugammadex and placebo. Doses would be based on actual body weight. The time taken to reach a TOF ratio of 0.9 thereafter would be measured. If the patient fails to achieve this goal by 10 minutes, sugammadex would be given in 2 mg/kg increments until the patient reaches this threshold and can be safely extubated. |
Experimental: Sugammadex 0.25 mg/kg
The study team will identify patients who are scheduled to undergo an elective surgery under general anesthesia, received rocuronium for NMB and neostigmine for NMB reversal. Patients will be randomized using the Emory University REDCap (Research Electronic Data Capture) software to six groups: 2 mg/kg (the lowest dose approved by the FDA), 1 mg/kg, 0.5 mg/kg, 0.25 mg/kg, 0.125 mg/kg of sugammadex and placebo. Doses would be based on actual body weight. The time taken to reach a TOF ratio of 0.9 thereafter would be measured. If the patient fails to achieve this goal by 10 minutes, sugammadex would be given in 2 mg/kg increments until the patient reaches this threshold and can be safely extubated. The TOF ratio would be measured again at 30 minutes after arrival at the PACU to exclude delayed residual NMB with the plan to give further 2 mg/kg doses of sugammadex if detected. |
Sugammadex is a FDA-approved drug that is in routine clinical use for NMB reversal. Patients will be randomized to six groups: 2 mg/kg (the lowest dose approved by the FDA), 1 mg/kg, 0.5 mg/kg, 0.25 mg/kg, 0.125 mg/kg of sugammadex and placebo. Doses would be based on actual body weight. The time taken to reach a TOF ratio of 0.9 thereafter would be measured. If the patient fails to achieve this goal by 10 minutes, sugammadex would be given in 2 mg/kg increments until the patient reaches this threshold and can be safely extubated. |
Experimental: Sugammadex 0.125 mg/kg
The study team will identify patients who are scheduled to undergo an elective surgery under general anesthesia, received rocuronium for NMB and neostigmine for NMB reversal. Patients will be randomized using the Emory University REDCap (Research Electronic Data Capture) software to six groups: 2 mg/kg (the lowest dose approved by the FDA), 1 mg/kg, 0.5 mg/kg, 0.25 mg/kg, 0.125 mg/kg of sugammadex and placebo. Doses would be based on actual body weight. The time taken to reach a TOF ratio of 0.9 thereafter would be measured. If the patient fails to achieve this goal by 10 minutes, sugammadex would be given in 2 mg/kg increments until the patient reaches this threshold and can be safely extubated. The TOF ratio would be measured again at 30 minutes after arrival at the PACU to exclude delayed residual NMB with the plan to give further 2 mg/kg doses of sugammadex if detected. |
Sugammadex is a FDA-approved drug that is in routine clinical use for NMB reversal. Patients will be randomized to six groups: 2 mg/kg (the lowest dose approved by the FDA), 1 mg/kg, 0.5 mg/kg, 0.25 mg/kg, 0.125 mg/kg of sugammadex and placebo. Doses would be based on actual body weight. The time taken to reach a TOF ratio of 0.9 thereafter would be measured. If the patient fails to achieve this goal by 10 minutes, sugammadex would be given in 2 mg/kg increments until the patient reaches this threshold and can be safely extubated. |
Placebo Comparator: Placebo
The inclusion of a placebo group would allow the study team to examine if patients may recover spontaneously over that time without needing any sugammadex at all, and what parameters may predict that subset of patients.
It will also improve the dose response modelling, in that randomization has been weighted so that patients who are least likely to need sugammadex (i.e. if they achieved a TOF count of 4 twitches without fade) are more likely to be in the placebo group or at the lowest dose of sugammadex that is being tested.
|
Normal saline will be used as placebo.
The inclusion of a placebo group would allow us to examine if patients may recover spontaneously over that time without needing any sugammadex at all, and what parameters may predict that subset of patients.
It will also improve the dose response modelling, in that randomization has been weighted so that patients who are least likely to need sugammadex (i.e. if they achieved a TOF count of 4 twitches without fade) are more likely to be in the placebo group or at the lowest dose of sugammadex that is being tested.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The time taken to achieve a TOF ratio of 0.9 after administration sugammadex
Time Frame: 10 minutes post administration of study drug
|
The time taken to achieve a time of train (TOF) ratio of 0.9 after the use of the intervention drug versus placebo in a patient population that has already received neostigmine for NMB reversal. Quantitative neuromuscular monitoring will be carried out using electromyography, which measures the TOF ratio every 20 seconds. The TOF count (between 0 to 4) and the TOF ratio (0 to 1) would be measured and recorded at baseline and after administration of the study drug. If the TOF ratio remains < 0.9 after this, or if the patient exhibits any symptoms or signs of residual NMB blockade, a further 2 mg/kg dose of sugammadex would be given until the patient achieves a TOF ratio of 0.9. |
10 minutes post administration of study drug
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The percentage of patients who achieve a TOF ratio of 0.9
Time Frame: 1 minute, 2 minutes and 10 minutes post administration of study drug
|
The percentage of patients who achieve a TOF ratio of 0.9 will be measured within 1 minute, 2 minutes, 5 minutes, and 10 minutes after the administration of the study drug, sugammadex.
|
1 minute, 2 minutes and 10 minutes post administration of study drug
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Rebecca Wong, M.B.B.S, Assistant Professor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- STUDY00004369
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
Researchers who provide a methodologically sound proposal, to achieve aims in the approved proposal.
Proposals should be directed to Dr. Rebecca Y S Wong at rywong@emory.edu. To gain access, data requestors will need to sign a data access agreement.
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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