Sugammadex vs Neostigmine for Neuromuscular Blockade

Overseen By Aline Reuter Pimenta

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The Cleveland Clinic

Disqualifiers: Neuromuscular disorders, End stage renal disease, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 1 day

80 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigators propose a single-center,assessor-Blinded, parallel group randomized trial to compare the efficacy of reversal of rocuronium induced neuromuscular blockade by sugammadex versus neostigmine in patients undergoing Endoscopic retrograde cholangiopancreatography at Cleveland Clinic Main Campus.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators.

What data supports the effectiveness of the drug Sugammadex compared to Neostigmine for reversing neuromuscular blockade?

Research shows that Sugammadex can reverse neuromuscular blockade more quickly and reliably than Neostigmine, especially in patients undergoing surgery. This means it may help patients recover from anesthesia more effectively, reducing the risk of breathing problems after surgery. ^{1 2 3 4 5}

What safety data exists for Sugammadex and Neostigmine in humans?

Both Sugammadex and Neostigmine can cause side effects like slow heart rate, severe allergic reactions, breathing difficulties, and even heart problems. Sugammadex generally has fewer drug-related side effects compared to Neostigmine, but there are still concerns about breathing and heart-related issues. ^{1 6 7 8 9}

How does the drug sugammadex differ from neostigmine for reversing neuromuscular blockade?

Sugammadex works faster and more reliably than neostigmine in reversing neuromuscular blockade, especially in morbidly obese patients undergoing bariatric surgery. Unlike neostigmine, sugammadex is a selective antagonist that can effectively reverse the block even when inhalational anesthetics are used, potentially reducing postoperative pulmonary complications. ^{1 2 5 10 11}

Research Team

Ryu Komatsu, MD

Principal Investigator

The Cleveland Clinic

Eligibility Criteria

This trial is for adults over 18 who are in moderate to severe physical condition (ASA status 3-4) and scheduled for an outpatient procedure called endoscopic retrograde cholangiopancreatography at Cleveland Clinic Main Campus.

Inclusion Criteria

I have a serious but not life-threatening illness.

I am scheduled for an ERCP procedure.

Exclusion Criteria

Difficult Airway

Pregnancy or breast-feeding

Allergy to Fentanyl

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo outpatient ERCP with general anesthesia and rocuronium-induced muscle relaxation, followed by reversal with either sugammadex or neostigmine

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of discharge readiness and incidence of postoperative nausea and vomiting

24 hours

1 visit (in-person)

Treatment Details

Interventions

• Neostigmine
• Sugammadex

Trial Overview The study compares two drugs, sugammadex and neostigmine, to see which one is better at reversing muscle relaxation caused by rocuronium during the specified medical procedure. Participants will be randomly assigned to receive either drug without knowing which one they get.

Participant Groups

Group I: 2 mg/kg sugammadex Experimental Treatment 1 Intervention

All participants will be given rocuromium for neuromuscular blocks during the procedure. Per randomization, patients in this group will be reversed with 2 mg/kg sugammadex.

Group II: 0.07 mg/kg neostigmine Active Control 1 Intervention

All participants will be given rocuromium for neuromuscular blocks during the procedure. Per randomization, patients in this group will be reversed with 0.07 mg/kg neostigmine (to a maximum of 5 mg).

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

Using sugammadex instead of neostigmine for reversing neuromuscular block in the operating room can significantly reduce the risk of residual neuromuscular blockade (RNMB) from 60% to just 4%, preventing complications like hypoxemia and airway obstruction.

In scenarios where full neuromuscular recovery is verified before extubation, sugammadex can improve operating room efficiency by saving an average of 62 minutes per day and reducing staff overtime by 33.5 hours, while also avoiding procedural cancellations due to time overruns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A discrete event simulation model of clinical and operating room efficiency outcomes of sugammadex versus neostigmine for neuromuscular block reversal in Canada. Insinga, RP., Joyal, C., Goyette, A., et al.[2018]

In a study of 68 morbidly obese patients undergoing bariatric surgery, sugammadex (SM) was found to significantly reduce the time to extubation and recovery compared to neostigmine (NT), indicating its efficacy in reversing neuromuscular block more effectively.

Both SM and NT showed similar safety profiles, with no significant differences in adverse effects such as respiratory difficulties or hemodynamic changes, suggesting that SM may be a safer option for this high-risk patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neostigmine versus sugammadex on post-operative recovery following bariatric surgery. Ekinci, O., Gulmez, DD., Subasi, FD., et al.[2022]

Sugammadex provides rapid and predictable reversal of neuromuscular blockade induced by rocuronium and vecuronium, with recovery times significantly shorter than those achieved with neostigmine, as shown in a pooled analysis of 26 studies involving 1855 adults.

The efficacy of sugammadex was consistent across different patient populations, demonstrating effective reversal even in cases of mild-to-moderate renal impairment and varying geographic locations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sugammadex efficacy for reversal of rocuronium- and vecuronium-induced neuromuscular blockade: A pooled analysis of 26 studies. Herring, WJ., Woo, T., Assaid, CA., et al.[2018]

Sugammadex appears to have more tolerable effects on kidney function compared to neostigmine in patients undergoing elective surgery, as indicated by differences in postoperative kidney markers like cystatin C.

Both sugammadex and neostigmine do not cause renal failure, but they can negatively affect kidney function, highlighting the importance of monitoring kidney health during and after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Sugammadex and Neostigmine on Renal Biomarkers. Isik, Y., Palabiyik, O., Cegin, BM., et al.[2019]

Sugammadex significantly reduces the recovery time from neuromuscular blockade in morbidly obese patients undergoing bariatric surgery, taking an average of 2.5 minutes compared to 18.2 minutes with neostigmine.

Patients receiving sugammadex experienced fewer adverse events (21.2%) compared to those treated with neostigmine (52.5%), indicating a safer profile for sugammadex in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Sugammadex versus Neostigmine in Reversing Neuromuscular Blockade in Morbidly Obese Adult Patients: A Systematic Review and Meta-Analysis. Subramani, Y., Querney, J., He, S., et al.[2022]

Sugammadex is significantly more effective than neostigmine in reversing neuromuscular blockade, reducing signs of residual paralysis and minor respiratory events in a review of 17 trials with 1553 participants.

Sugammadex also leads to fewer drug-related side effects compared to neostigmine, although it does not significantly affect rates of postoperative nausea or vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of sugammadex vs neostigmine for reversal of neuromuscular blockade. Abad-Gurumeta, A., Ripollés-Melchor, J., Casans-Francés, R., et al.[2022]

Sugammadex is associated with fewer cases of bradycardia compared to neostigmine in pediatric patients, indicating a potentially safer profile for reversing neuromuscular blockade.

The use of sugammadex resulted in significantly shorter recovery times from anesthesia, especially in neonates, suggesting it is more effective than neostigmine for this purpose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Analysis of the Safety and Efficacy of Sugammadex Versus Neostigmine for the Reversal of Neuromuscular Blockade in Children. Gaver, RS., Brenn, BR., Gartley, A., et al.[2020]

In a study of 89,753 surgeries involving 70,690 patients, sugammadex was found to have a slightly higher incidence of clinically meaningful side effects (3.4%) compared to neostigmine (3.0%), but the difference was minimal (0.4%).

Neostigmine was statistically superior to sugammadex in terms of safety, with an odds ratio of 0.83 for the composite of side effects, indicating that while neostigmine may be safer, the clinical significance of the difference is small, requiring 250 patients to be treated with neostigmine to prevent one minor complication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sugammadex Versus Neostigmine for Reversal of Residual Neuromuscular Blocks After Surgery: A Retrospective Cohort Analysis of Postoperative Side Effects. Ruetzler, K., Li, K., Chhabada, S., et al.[2023]

A retrospective analysis of the FDA's Adverse Event Reporting System revealed a significant association between sugammadex and bronchospasm, with a reporting odds ratio indicating a strong link (PRR = 71.95).

There is also a notable association between sugammadex and coronary arteriospasm, with a significant disproportionality signal (PRR = 43.82), suggesting that healthcare providers should be cautious and monitor for these adverse events when administering sugammadex.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of bronchospasm and coronary arteriospasm with sugammadex use: a post marketing analysis. Aggarwal, P.[2022]

Sugammadex significantly accelerates the discharge process for patients after general anesthesia compared to neostigmine, with a mean difference of 22.14 minutes from the operating room to the postanesthesia care unit (PACU) and 16.95 minutes from the PACU to the surgical ward.

The study analyzed data from 518 patients across six randomized controlled trials, indicating that while sugammadex improves discharge times, the readiness for discharge from the PACU to the surgical ward was similar for both sugammadex and neostigmine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of sugammadex in accelerating postoperative discharge: A meta-analysis. Carron, M., Zarantonello, F., Lazzarotto, N., et al.[2018]

In a study of 1,672 patients undergoing elective surgery, those who received sugammadex after neostigmine had a higher rate of postoperative pulmonary complications (6.8%) compared to those who received sugammadex alone (3.1%).

The findings suggest that using sugammadex as a rescue agent after neostigmine may increase the risk of complications, indicating a need for further investigation into the safety and efficacy of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emergency use of sugammadex after failure of standard reversal drugs and postoperative pulmonary complications: A retrospective cohort study. Bruceta, M., Singh, PM., Bonavia, A., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

A discrete event simulation model of clinical and operating room efficiency outcomes of sugammadex versus neostigmine for neuromuscular block reversal in Canada. [2018]

2. Turkey pubmed.ncbi.nlm.nih.gov

Neostigmine versus sugammadex on post-operative recovery following bariatric surgery. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Sugammadex efficacy for reversal of rocuronium- and vecuronium-induced neuromuscular blockade: A pooled analysis of 26 studies. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Effects of Sugammadex and Neostigmine on Renal Biomarkers. [2019]

5. India pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Sugammadex versus Neostigmine in Reversing Neuromuscular Blockade in Morbidly Obese Adult Patients: A Systematic Review and Meta-Analysis. [2022]

6. England pubmed.ncbi.nlm.nih.gov

A systematic review of sugammadex vs neostigmine for reversal of neuromuscular blockade. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Retrospective Analysis of the Safety and Efficacy of Sugammadex Versus Neostigmine for the Reversal of Neuromuscular Blockade in Children. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Sugammadex Versus Neostigmine for Reversal of Residual Neuromuscular Blocks After Surgery: A Retrospective Cohort Analysis of Postoperative Side Effects. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Risk of bronchospasm and coronary arteriospasm with sugammadex use: a post marketing analysis. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Role of sugammadex in accelerating postoperative discharge: A meta-analysis. [2018]

11. India pubmed.ncbi.nlm.nih.gov

Emergency use of sugammadex after failure of standard reversal drugs and postoperative pulmonary complications: A retrospective cohort study. [2023]