Spine SurgeryPhase 4NCT03112993
Speed of Recovery of Reversal of Neuromuscular Blockade in Geriatric Patients Undergoing Spine Surgery
A Phase 4 study testing sugammadex and Neostigmine in people with Spine Surgery, run by University of Missouri-Columbia at 1 site in United States.
Trial summary
Spine surgery is one of the most common operative procedures in the United States. It is performed in the prone position (a patient laying on belly). Muscle relaxants are given for neuromuscular blockade often referred as paralysis for surgical exposure which is maintained until the patient is returned to the supine… Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Spine Surgery
- What is being tested?
- sugammadex and Neostigmine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 30 May 2017to 14 Aug 2018
- 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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Posterior spinal surgery
- Age ≥ 65 years
- American Society of Anesthesiologists (ASA) grade I-III
Who cannot join
- Inability to obtain written informed consent
- Allergy to rocuronium or anesthetic agents used in the protocol
- Known or suspected neuromuscular disorders
- Significant renal disease with a serum creatinine ≥ 2 mg/dl
- Significant liver disease
- A family history of malignant hyperthermia
Trial locations and contacts
1 site in 1 country.
United States1 site
University on Missouri Hospital
Columbia, Missouri, 65212
About this study
Official title: A Prospective, Randomized, Double-Blind Clinical Trial Evaluating the Speed of Recovery and Safety of Reversal of Neuromuscular Blockade With Sugammadex (Bridion™) Versus Neostigmine in Geriatric Patients Undergoing Spine Surgery
Spine surgery is one of the most common operative procedures in the United States. It is performed in the prone position (a patient laying on belly). Muscle relaxants are given for neuromuscular blockade often referred as paralysis for surgical exposure which is maintained until the patient is returned to the supine position (a patient laying on back) at the end of surgery. At the end of the surgery the paralysis is reversed with a drug (neostigmine). A new drug (sugammadex) has the ability to rapidly reverse the paralysis but it is not well investigated in elderly. This study will investigate speed of recovery and complications of the two reversal drugs in elderly patients (age ≥ 65 years) undergoing posterior spine surgery.
Read the detailed description
The elderly (age ≥ 65 years) population is the fastest growing segment of the American population. Spine surgery is one of the most common operative procedures in the United States and, as the population ages, a larger percentage of geriatric patients will require this procedure. In addition, spinal surgery is often more complex in the elderly population, resulting in longer surgical times. A previous study reported that the rate of complex procedures increased 15-fold in Medicare recipients. Spine surgery is performed in the prone position and neuromuscular blockade (NMB) is maintained until the patient is returned to the supine position at the end of surgery to avoid the risk of patient movement, injury, and inadvertent tracheal extubation while prone. Currently, NMB is reversed with neostigmine immediately after turning the patients back to the supine position at the end of the procedure.
Rocuronium bromide, an intermediate-acting neuromuscular blocking agent (NMBA), is used in approximately 60% of surgical cases in the United States and is commonly used for muscle relaxation during spinal surgery. With aging, the clearance and half-life of rocuronium is prolonged resulting in a wide variability in the duration of action and time to reversal. Until recently, the only medication available for the reversal of neuromuscular blockade was neostigmine and postoperative residual neuromuscular block (PRNB) was common, especially in elderly patients. A recent study reported that PRNB occurred in 58% of elderly patients who were maintained at a moderate level (2 twitches in the TOF) of muscle relaxation with rocuronium during elective surgery. As a result, these older adults experienced an increased incidence of airway obstruction, hypoxemic events, muscle weakness, postoperative pulmonary complications, and increased PACU and hospital lengths of stay.
A new neuromuscular reversal agent sugammadex (Bridion®) has the ability to rapidly reverse both moderate and deep rocuronium-induced NMB. Another study reported that the mean time to complete reversal (TOF ratio ≥ 0.9) of a moderate block (2 twitches in the TOF) with sugammadex in geriatric patients was 2.9 minutes, which was only 1 minute longer than in younger patients. Reversal of NMB with neostigmine is much slower and it is reported to take approximately 19 minutes to achieve complete reversal in middle-aged patients. There is little available data on the NMB reversal time in older adults, but it will likely be even longer because the age-related physiologic changes prolong neuromuscular recovery. Thus, sugammadex has the potential to more rapidly reverse NMB in geriatric patients at the end of surgery. As a result, the use of sugammadex should decrease time in the OR and possibly PACU time and result in cost savings.
Neostigmine has cardiac muscarinic effects and, therefore, has to be administered with an anticholinergic agent such as glycopyrrolate to counteract these effects. A previous study found a 16% incidence of cardiac dysrhythmias in elderly patients who received neostigmine/glycopyrrolate NMB reversal. The ability of sugammadex to completely reverse NMB without the addition of an anticholinesterase agent should result in an improved safety profile in elderly patients.
The goal of this prospective, randomized, double-blinded controlled trial is to test the hypothesis that the reversal of neuromuscular blockage with sugammadex as compared to neostigmine in geriatric patients will provide a shorter time to complete recovery of neuromuscular function, improve the workflow in the operating room and decrease operative costs.
- Conditions
- Spine Surgery
- Being tested
- sugammadex, Neostigmine
- Keywords
- spine surgery, neuromuscular blockade, sugammadex, elderly, reversal, neostigmine, recovery
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sugammadexDrug
Also called Bridion
once at the end of the surgery
NeostigmineDrug
once at the end of the surgery
| Study group | Role | What they receive |
|---|---|---|
| Sugammadex group | Experimental | 2 mg/kg of sugammadex, IV once at the end of the surgery. Dosing will be based on actual body weight not ideal body weight. Receives: Drug: sugammadex |
| Neostigmine group | Active comparator | 50 micrograms/kg (not to exceed 5 mg) and glycopyrrolate, 10 micrograms/kg (not to exceed 1 mg), IV once at the end of the surgery.
Dosing will be based on actual body weight not ideal body weight. Receives: Drug: Neostigmine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in Time of Neuromuscular Recovery From a Neuromuscular Moderate Blockade
Speed of neuromuscular recovery in minutes measured by recovery of the T4:T1 ratio ≥ 0.9 (measured with a TOF-Watch SX)
Measured: Day 1
Difference in Time From Neuromuscular Reversal to Exit From OR
Difference in time from neuromuscular reversal to exit from OR was measured in minutes.
Measured: Day 1
Secondary outcomes (2)
Difference in Time From Neuromuscular Reversal to Tracheal Extubation
Difference in time from neuromuscular reversal to tracheal extubation was measured in minutes.
Measured: Day 1
Difference in Length of Stay in PACU
Length of PACU stay measured in minutes.
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2017
- Study start30 May 2017
- Primary completion13 Aug 2018
- Study completion14 Aug 2018
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 Spine SurgeryStudies of the same condition, open and under way.
- More trials run by University of Missouri-ColumbiaThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will receive (per a randomization schedule) either sugammadex, or neostigmine/glycopyrrolate to reverse neuromuscular blockade at the end of the surgery. The reversal agent will be prepared in a blinded fashion.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Missouri-Columbia
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Boris Mraovic, University of Missouri-Columbia
- Investigators
- Boris Mraovic, MD, Principal investigator, Univesity of Missouri-Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03112993
- Sponsor's protocol ID
- IRB # 2008066
- Other IDs
- MISP # 56051.
- Status last verified
- Mar 2022
- First submitted
- 29 Mar 2017
- Last updated
- 1 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mraovic B, Timko NJ, Choma TJ. Comparison of recovery after sugammadex or neostigmine reversal of rocuronium in geriatric patients undergoing spine surgery: a randomized controlled trial. Croat Med J. 2021 Dec 31;62(6):606-613. doi: 10.3325/cmj.2021.62.606.
PubMed 34981693
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized, Double-Blind Clinical Trial Evaluating the Speed of Recovery and Safety of Reversal of Neuromuscular Blockade With Sugammadex (Bridion™) Versus Neostigmine in Geriatric Patients Undergoing Spine Surgery
- ClinicalTrials.gov ID
- NCT03112993
- Acronym / sponsor ID
- IRB # 2008066
- Conditions
- Spine Surgery
- Keywords
- spine surgery, neuromuscular blockade, sugammadex, elderly, reversal, neostigmine, recovery
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University of Missouri-ColumbiaUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 30 May 2017 (actual)
- Primary completion
- 13 Aug 2018 (actual)
- Study completion
- 14 Aug 2018 (actual)
- First posted
- 13 Apr 2017 (actual)
- Results
- Posted 10 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Spine surgery is one of the most common operative procedures in the United States. It is performed in the prone position (a patient laying on belly). Muscle relaxants are given for neuromuscular blockade often referred as paralysis for surgical exposure which is maintained until the patient is returned to the supine position (a patient laying on back) at the end of surgery. At the end of the surgery the paralysis is reversed with a drug (neostigmine). A new drug (sugammadex) has the ability to rapidly reverse the paralysis but it is not well investigated in elderly. This study will investigate speed of recovery and complications of the two reversal drugs in elderly patients (age ≥ 65 years) undergoing posterior spine surgery.
Detailed description
The elderly (age ≥ 65 years) population is the fastest growing segment of the American population. Spine surgery is one of the most common operative procedures in the United States and, as the population ages, a larger percentage of geriatric patients will require this procedure. In addition, spinal surgery is often more complex in the elderly population, resulting in longer surgical times. A previous study reported that the rate of complex procedures increased 15-fold in Medicare recipients. Spine surgery is performed in the prone position and neuromuscular blockade (NMB) is maintained until the patient is returned to the supine position at the end of surgery to avoid the risk of patient movement, injury, and inadvertent tracheal extubation while prone. Currently, NMB is reversed with neostigmine immediately after turning the patients back to the supine position at the end of the procedure.
Rocuronium bromide, an intermediate-acting neuromuscular blocking agent (NMBA), is used in approximately 60% of surgical cases in the United States and is commonly used for muscle relaxation during spinal surgery. With aging, the clearance and half-life of rocuronium is prolonged resulting in a wide variability in the duration of action and time to reversal. Until recently, the only medication available for the reversal of neuromuscular blockade was neostigmine and postoperative residual neuromuscular block (PRNB) was common, especially in elderly patients. A recent study reported that PRNB occurred in 58% of elderly patients who were maintained at a moderate level (2 twitches in the TOF) of muscle relaxation with rocuronium during elective surgery. As a result, these older adults experienced an increased incidence of airway obstruction, hypoxemic events, muscle weakness, postoperative pulmonary complications, and increased PACU and hospital lengths of stay.
A new neuromuscular reversal agent sugammadex (Bridion®) has the ability to rapidly reverse both moderate and deep rocuronium-induced NMB. Another study reported that the mean time to complete reversal (TOF ratio ≥ 0.9) of a moderate block (2 twitches in the TOF) with sugammadex in geriatric patients was 2.9 minutes, which was only 1 minute longer than in younger patients. Reversal of NMB with neostigmine is much slower and it is reported to take approximately 19 minutes to achieve complete reversal in middle-aged patients. There is little available data on the NMB reversal time in older adults, but it will likely be even longer because the age-related physiologic changes prolong neuromuscular recovery. Thus, sugammadex has the potential to more rapidly reverse NMB in geriatric patients at the end of surgery. As a result, the use of sugammadex should decrease time in the OR and possibly PACU time and result in cost savings.
Neostigmine has cardiac muscarinic effects and, therefore, has to be administered with an anticholinergic agent such as glycopyrrolate to counteract these effects. A previous study found a 16% incidence of cardiac dysrhythmias in elderly patients who received neostigmine/glycopyrrolate NMB reversal. The ability of sugammadex to completely reverse NMB without the addition of an anticholinesterase agent should result in an improved safety profile in elderly patients.
The goal of this prospective, randomized, double-blinded controlled trial is to test the hypothesis that the reversal of neuromuscular blockage with sugammadex as compared to neostigmine in geriatric patients will provide a shorter time to complete recovery of neuromuscular function, improve the workflow in the operating room and decrease operative costs.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will receive (per a randomization schedule) either sugammadex, or neostigmine/glycopyrrolate to reverse neuromuscular blockade at the end of the surgery. The reversal agent will be prepared in a blinded fashion.
| Arm | Type | Receives |
|---|---|---|
| Sugammadex group | Experimental | Drug: sugammadex2 mg/kg of sugammadex, IV once at the end of the surgery. Dosing will be based on actual body weight not ideal body weight. |
| Neostigmine group | Active comparator | Drug: Neostigmine50 micrograms/kg (not to exceed 5 mg) and glycopyrrolate, 10 micrograms/kg (not to exceed 1 mg), IV once at the end of the surgery. Dosing will be based on actual body weight not ideal body weight. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (3 listed)
- Posterior spinal surgery
- Age ≥ 65 years
- American Society of Anesthesiologists (ASA) grade I-III
Key exclusion criteria (6 listed)
- Inability to obtain written informed consent
- Allergy to rocuronium or anesthetic agents used in the protocol
- Known or suspected neuromuscular disorders
- Significant renal disease with a serum creatinine ≥ 2 mg/dl
- Significant liver disease
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 |
|---|---|---|
| sugammadexAlso: Bridiononce at the end of the surgery | Drug | Sugammadex group |
| Neostigmineonce at the end of the surgery | Drug | Neostigmine group |
Primary outcome
Difference in Time of Neuromuscular Recovery From a Neuromuscular Moderate Blockade
Time frame: Day 1
Speed of neuromuscular recovery in minutes measured by recovery of the T4:T1 ratio ≥ 0.9 (measured with a TOF-Watch SX)
Difference in Time From Neuromuscular Reversal to Exit From OR
Time frame: Day 1
Difference in time from neuromuscular reversal to exit from OR was measured in minutes.
2 secondary outcomes
Difference in Time From Neuromuscular Reversal to Tracheal Extubation
Time frame: Day 1
Difference in Length of Stay in PACU
Time frame: Day 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 34981693Mraovic B, Timko NJ, Choma TJ. Comparison of recovery after sugammadex or neostigmine reversal of rocuronium in geriatric patients undergoing spine surgery: a randomized controlled trial. Croat Med J. 2021 Dec 31;62(6):606-613. doi: 10.3325/cmj.2021.62.606.
- Individual participant dataSharing planned: No
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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.
Boris Mraovic, MD principal investigator
Univesity of Missouri-Columbia
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 sugammadex and Neostigmine in people with Spine Surgery, run by University of Missouri-Columbia 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 3 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 1 Apr 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 10 Feb 2020). 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?
Difference in Time of Neuromuscular Recovery From a Neuromuscular Moderate Blockade (time frame: Day 1). The study lists 2 primary outcomes in all. 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 NCT03112993, 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 1 Apr 2022; AzTrials last refreshed its copy on 8 Nov 2026.