Residual Paralysis, Post AnesthesiaPhase 4NCT03958201
Best Management of Muscle Relaxation- Objective Monitoring
A Phase 4 study testing Protocol for Management of Muscle Relaxation With Rocuronium Using Objective Monitoring and Reversal With Neostigmine or Sugammadex in people with Residual Paralysis, Post Anesthesia, run by University of Washington at 1 site in United States.
Trial summary
The purpose of this study is to demonstrate that the investigators can reduce residual paralysis to a very low incidence, and that the investigators can do this while preserving a role for the older and less expensive reversal agent neostigmine. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Residual Paralysis, Post Anesthesia
- What is being tested?
- Protocol for Management of Muscle Relaxation With Rocuronium Using Objective Monitoring and Reversal With Neostigmine or Sugammadex
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 28 May 2019to 31 Mar 2020
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Are 18 years or older
- Undergoing surgery expected to last less than 6 hours at HMC or UWMC
- Have ASA physical status I-III
- Scheduled to have general anesthesia with at least 1 dose of nondepolarizing NMBD for endotracheal intubation or intraoperative neuromuscular block (NMB)
Who cannot join
- Allergy to NMBDs, neostigmine, or sugammadex
- Patients with neuromuscular disease (myasthenia gravis or muscular dystrophy)
- Pregnant or lactating women
- Non English speaking
- Unable to provide informed consent
- Severe renal failure with eGFR less than 20 ml/min
Trial locations and contacts
1 site in 1 country.
United States1 site
Harborview Medical Center
Seattle, Washington, 98104
About this study
Official title: Best Management of Muscle Relaxation With Rocuronium Using Objective Monitoring and Reversal With Neostigmine or Sugammadex
The purpose of this study is to demonstrate that the investigators can reduce residual paralysis to a very low incidence, and that the investigators can do this while preserving a role for the older and less expensive reversal agent neostigmine. The investigators consider this an evidence-based approach because previous reports clearly indicate that neostigmine is effective for reversal of the most shallow neuromuscular blocks, a level of block now referred to as minimal block. The Investigators also know from previous data that a substantial proportion of patients have minimal block. Sugammadex will be used when the block to be reversed is deeper than minimal, specifically when the objectively measured TOF-ratio is <40%.
The investigators hypothesize that this protocol will be associated with an incidence of residual paralysis of less than 3%. The investigators plan is to study 200 patients.
Read the detailed description
This study implements a standardized protocol for NMBD (neuromuscular blocking drug) management that is currently used by some providers at UWMC and HMC to help prevent residual paralysis in surgical patients. While this protocol is within the scope of routine care that an anesthesiologist could follow in his/her clinical practice, it is not consistently used throughout HMC and UWMC. This protocol follows clinical best practices for NMBD management in a surgical population and adheres to the recommendations from the P\&T committee on reversal drug choice and recommendations from the Department of Anesthesiology and Pain Medicine on neostigmine dosing. While this protocol is in line with best practices, the investigators are continuing to systematically evaluate it in the setting of prospective research. All drugs will be administered for clinical care only. This research does not add additional medications. The study will take place at UWMC and HMC and will follow a standardized research protocol for the timing, dosing, and monitoring surrounding muscle relaxants and reversal, and makes use of objective TOF monitors. If a patient agrees to participate in this study, the following research protocol will occur:
Before Surgery:
- TOF measurements before surgery: A study investigator will perform the routine clinical train-of-four measurements with an objective monitor at baseline after the clinical induction of general anesthesia but before the administration of the NMBD. Information will be recorded for research purposes. Research staff will leave the operating room after obtaining the baseline measurement and will return to the operating room at the end of the surgical procedure, to be available for TOF ratio measurements at the time that reversal of paralysis is planned as well as for the primary outcome measurement, i.e. at time of extubation.
- Dose calculation of initial NMBD: A study investigator will assist the anesthesia provider with calculation of the recommended intubating dose of rocuronium (an NMBD). The dose will be calculated per this research protocol based on Ideal Body Weight (IBW).
- For women 45.5 kg plus 2.3 kg/inch over 5 feet of height
- For men 50 kg plus 2.3 kg/inch over 5 feet of height.
- For routine intubations, the recommended dose for intubation will be a maximum of Rocuronium 0.6 mg/kg.
- The intubating dose will be reduced by 15% for females.
- Higher intubating dose may be used at the discretion of the anesthesia provider
During Surgery:
- Additional dose calculation of NMBD: Each additional dose of rocuronium will be 25% of the recommended intubating dose and will be administered when the TOF count has returned to at least 2, the aim is to maintain an intraoperative TOF count of 1-2 unless the anesthesia provider has deemed deep paralysis to be necessary in which case a TOF count of 0 will be maintained. An attempt will be made to avoid administration of rocuronium during the last 30 minutes of the procedure.
After Surgery:
- Patients will receive reversal drugs for their routine care that will help reverse the effects of their muscle relaxant. In this study, the decision of reversal drug use will follow institutional guidelines. The timing and dose calculation of the reversal drug will follow the research protocol as follows:
- Timing of neostigmine or sugammadex: Based on the results of the clinical pre-reversal TOF assessment, reversal with neostigmine will be administered if the objective TOF-ratio is between 40%-90%. If the block is deeper than this, then sugammadex will be used for reversal (This is per institutional guidance on choice of reversal drug).
- Dose calculation of neostigmine and sugammadex: For this study, the dose of neostigmine will be calculated based on the IBW. The dose of sugammadex will be calculated based on patients' actual body weight. For all subjects enrolled in this study, the investigators will follow a dose schedule which is based on clinical TOF monitoring and is in accordance with institutional recommendations for dosing of neostigmine.
- Timing of extubation: The patient's trachea will not be extubated before routine objective monitoring confirms recovery to a TOF-ratio 90%. However, in the case that objective monitoring cannot be obtained by the provider then the following will happen:
- For subjects who receive neostigmine for their routine care, it is recommended that the patient's trachea will not be extubated earlier than 10 minutes after the administration of this drug.
- For subjects who receive sugammadex for routine care, it is recommended that the patient's trachea will not be extubated earlier than 3 minutes after drug administration.
- TOF measurements after surgery (extubation): The TOF-ratio will be measured by a study investigator or provider at the time of extubation. Information will be recorded for research purposes. If the investigators miss obtaining research measurements at the time of extubation, they will obtain TOF measurements on the patient's arrival to the PACU.
- Collection of data from EMR: the investigators will collect information from the patient's medical record including the intraoperative TOF counts, ASA class, surgical procedure, times of the surgical procedure, time and dose of administered medications, and the patient's temperature in the operating room and PACU.
- Conditions
- Residual Paralysis, Post Anesthesia
- Being tested
- Protocol for Management of Muscle Relaxation With Rocuronium Using Objective Monitoring and Reversal With Neostigmine or Sugammadex
- Medical subject headings
- Delayed Emergence from Anesthesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Protocol for Management of Muscle Relaxation With Rocuronium Using Objective Monitoring and Reversal With Neostigmine or SugammadexCombination product
The protocol includes specified appropriate rocuronium dosing and a valid pre-reversal assessment of the adductor pollicis response guides optimal neostigmine vs. sugammadex reversal.
| Study group | Role | What they receive |
|---|---|---|
| Protocol | Other | Patients will have perioperative neuromuscular block managed by protocol. The protocol includes specified appropriate rocuronium dosing and reversal with either neostigmine or sugammadex depending on depth of block as assessed objectively at adductor pollicis with quantitative neuromuscular monitoring. Receives: Combination Product: Protocol for Management of Muscle Relaxation With Rocuronium Using Objective Monitoring and Reversal With Neostigmine or Sugammadex |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Postoperative Residual Neuromuscular Blockade at Time of Extubation
Train-of-four ratio <0.9 as measured by electromyography or <1.0 measured by acceleromyography
Measured: Within two minutes of extubation
Secondary outcomes (1)
Incidence of Severe Postoperative Residual Neuromuscular Blockade at Time of Extubation
Train-of-four ratio <0.7 as measured by electromyography
Measured: Within two minutes of extubation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2019
- Study start28 May 2019
- Primary completion31 Jan 2020
- Study completion31 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Residual Paralysis, Post AnesthesiaStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Stephan Thilen, University of Washington
- Investigators
- Stephan R Thilen, MD, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03958201
- Sponsor's protocol ID
- STUDY00007084
- Status last verified
- Oct 2022
- First submitted
- 17 May 2019
- Last updated
- 2 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Thilen SR, Sherpa JR, James AM, Cain KC, Treggiari MM, Bhananker SM. Management of Muscle Relaxation With Rocuronium and Reversal With Neostigmine or Sugammadex Guided by Quantitative Neuromuscular Monitoring. Anesth Analg. 2024 Sep 1;139(3):536-544. doi: 10.1213/ANE.0000000000006511. Epub 2023 May 12.
PubMed 37171989
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Best Management of Muscle Relaxation With Rocuronium Using Objective Monitoring and Reversal With Neostigmine or Sugammadex
- ClinicalTrials.gov ID
- NCT03958201
- Acronym / sponsor ID
- STUDY00007084
- Conditions
- Residual Paralysis, Post Anesthesia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Study start
- 28 May 2019 (actual)
- Primary completion
- 31 Jan 2020 (actual)
- Study completion
- 31 Mar 2020 (actual)
- First posted
- 21 May 2019 (actual)
- Results
- Posted 2 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to demonstrate that the investigators can reduce residual paralysis to a very low incidence, and that the investigators can do this while preserving a role for the older and less expensive reversal agent neostigmine. The investigators consider this an evidence-based approach because previous reports clearly indicate that neostigmine is effective for reversal of the most shallow neuromuscular blocks, a level of block now referred to as minimal block. The Investigators also know from previous data that a substantial proportion of patients have minimal block. Sugammadex will be used when the block to be reversed is deeper than minimal, specifically when the objectively measured TOF-ratio is <40%.
The investigators hypothesize that this protocol will be associated with an incidence of residual paralysis of less than 3%. The investigators plan is to study 200 patients.
Detailed description
This study implements a standardized protocol for NMBD (neuromuscular blocking drug) management that is currently used by some providers at UWMC and HMC to help prevent residual paralysis in surgical patients. While this protocol is within the scope of routine care that an anesthesiologist could follow in his/her clinical practice, it is not consistently used throughout HMC and UWMC. This protocol follows clinical best practices for NMBD management in a surgical population and adheres to the recommendations from the P\&T committee on reversal drug choice and recommendations from the Department of Anesthesiology and Pain Medicine on neostigmine dosing. While this protocol is in line with best practices, the investigators are continuing to systematically evaluate it in the setting of prospective research. All drugs will be administered for clinical care only. This research does not add additional medications. The study will take place at UWMC and HMC and will follow a standardized research protocol for the timing, dosing, and monitoring surrounding muscle relaxants and reversal, and makes use of objective TOF monitors. If a patient agrees to participate in this study, the following research protocol will occur:
Before Surgery:
- TOF measurements before surgery: A study investigator will perform the routine clinical train-of-four measurements with an objective monitor at baseline after the clinical induction of general anesthesia but before the administration of the NMBD. Information will be recorded for research purposes. Research staff will leave the operating room after obtaining the baseline measurement and will return to the operating room at the end of the surgical procedure, to be available for TOF ratio measurements at the time that reversal of paralysis is planned as well as for the primary outcome measurement, i.e. at time of extubation.
- Dose calculation of initial NMBD: A study investigator will assist the anesthesia provider with calculation of the recommended intubating dose of rocuronium (an NMBD). The dose will be calculated per this research protocol based on Ideal Body Weight (IBW).
- For women 45.5 kg plus 2.3 kg/inch over 5 feet of height
- For men 50 kg plus 2.3 kg/inch over 5 feet of height.
- For routine intubations, the recommended dose for intubation will be a maximum of Rocuronium 0.6 mg/kg.
- The intubating dose will be reduced by 15% for females.
- Higher intubating dose may be used at the discretion of the anesthesia provider
During Surgery:
- Additional dose calculation of NMBD: Each additional dose of rocuronium will be 25% of the recommended intubating dose and will be administered when the TOF count has returned to at least 2, the aim is to maintain an intraoperative TOF count of 1-2 unless the anesthesia provider has deemed deep paralysis to be necessary in which case a TOF count of 0 will be maintained. An attempt will be made to avoid administration of rocuronium during the last 30 minutes of the procedure.
After Surgery:
- Patients will receive reversal drugs for their routine care that will help reverse the effects of their muscle relaxant. In this study, the decision of reversal drug use will follow institutional guidelines. The timing and dose calculation of the reversal drug will follow the research protocol as follows:
- Timing of neostigmine or sugammadex: Based on the results of the clinical pre-reversal TOF assessment, reversal with neostigmine will be administered if the objective TOF-ratio is between 40%-90%. If the block is deeper than this, then sugammadex will be used for reversal (This is per institutional guidance on choice of reversal drug).
- Dose calculation of neostigmine and sugammadex: For this study, the dose of neostigmine will be calculated based on the IBW. The dose of sugammadex will be calculated based on patients' actual body weight. For all subjects enrolled in this study, the investigators will follow a dose schedule which is based on clinical TOF monitoring and is in accordance with institutional recommendations for dosing of neostigmine.
- Timing of extubation: The patient's trachea will not be extubated before routine objective monitoring confirms recovery to a TOF-ratio 90%. However, in the case that objective monitoring cannot be obtained by the provider then the following will happen:
- For subjects who receive neostigmine for their routine care, it is recommended that the patient's trachea will not be extubated earlier than 10 minutes after the administration of this drug.
- For subjects who receive sugammadex for routine care, it is recommended that the patient's trachea will not be extubated earlier than 3 minutes after drug administration.
- TOF measurements after surgery (extubation): The TOF-ratio will be measured by a study investigator or provider at the time of extubation. Information will be recorded for research purposes. If the investigators miss obtaining research measurements at the time of extubation, they will obtain TOF measurements on the patient's arrival to the PACU.
- Collection of data from EMR: the investigators will collect information from the patient's medical record including the intraoperative TOF counts, ASA class, surgical procedure, times of the surgical procedure, time and dose of administered medications, and the patient's temperature in the operating room and PACU.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Protocol | Other | Combination Product: Protocol for Management of Muscle Relaxation With Rocuronium Using Objective Monitoring and Reversal With Neostigmine or SugammadexPatients will have perioperative neuromuscular block managed by protocol. The protocol includes specified appropriate rocuronium dosing and reversal with either neostigmine or sugammadex depending on depth of block as assessed objectively at adductor pollicis with quantitative neuromuscular monitoring. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Are 18 years or older
- Undergoing surgery expected to last less than 6 hours at HMC or UWMC
- Have ASA physical status I-III
- Scheduled to have general anesthesia with at least 1 dose of nondepolarizing NMBD for endotracheal intubation or intraoperative neuromuscular block (NMB)
Key exclusion criteria (6 listed)
- Allergy to NMBDs, neostigmine, or sugammadex
- Patients with neuromuscular disease (myasthenia gravis or muscular dystrophy)
- Pregnant or lactating women
- Non English speaking
- Unable to provide informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Protocol for Management of Muscle Relaxation With Rocuronium Using Objective Monitoring and Reversal With Neostigmine or SugammadexThe protocol includes specified appropriate rocuronium dosing and a valid pre-reversal assessment of the adductor pollicis response guides optimal neostigmine vs. sugammadex reversal. | Combination product | Protocol |
Primary outcome
Incidence of Postoperative Residual Neuromuscular Blockade at Time of Extubation
Time frame: Within two minutes of extubation
Train-of-four ratio <0.9 as measured by electromyography or <1.0 measured by acceleromyography
1 secondary outcome
Incidence of Severe Postoperative Residual Neuromuscular Blockade at Time of Extubation
Time frame: Within two minutes of extubation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37171989Thilen SR, Sherpa JR, James AM, Cain KC, Treggiari MM, Bhananker SM. Management of Muscle Relaxation With Rocuronium and Reversal With Neostigmine or Sugammadex Guided by Quantitative Neuromuscular Monitoring. Anesth Analg. 2024 Sep 1;139(3):536-544. doi: 10.1213/ANE.0000000000006511. Epub 2023 May 12.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephan R Thilen, MD principal investigator
University of Washington
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Protocol for Management of Muscle Relaxation With Rocuronium Using Objective Monitoring and Reversal With Neostigmine or Sugammadex in people with Residual Paralysis, Post Anesthesia, run by University of Washington at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Postoperative Residual Neuromuscular Blockade at Time of Extubation (time frame: Within two minutes of extubation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03958201, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2022.