Sugammadex vs Neostigmine for Neuromuscular Blockade

Overseen By Sandra Durbin

Age: 18+

Sex: Any

Trial Phase: Phase 3

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)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 1 day

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines two drugs, sugammadex and neostigmine, to determine which better aids recovery from muscle relaxation during endoscopic retrograde cholangiopancreatography (a test for the liver, gallbladder, bile ducts, and pancreas). The main goal is to identify which drug restores muscle function faster after relaxation with rocuronium. Suitable participants are those scheduled for this procedure and classified with specific health statuses by their doctors. As a Phase 3 trial, this study represents the final step before FDA approval, allowing participants to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that sugammadex is generally safe for reversing muscle relaxation after surgery. Studies have found it causes fewer side effects, such as a slow heart rate and less nausea, compared to other treatments. Patients often recover quickly, typically within a few minutes.

Neostigmine, another long-used treatment, works well but can cause side effects like a slow heart rate and increased saliva, which may be uncomfortable.

Both treatments have been tested in patients and are considered safe. However, sugammadex may offer a smoother recovery with fewer side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about sugammadex because it offers a new way to reverse neuromuscular blockade. Unlike the traditional treatment, neostigmine, which works indirectly by increasing the levels of acetylcholine to outcompete the blocking agents, sugammadex directly encapsulates and inactivates the neuromuscular blocking agents like rocuronium. This unique mechanism allows for a faster and more predictable recovery from muscle paralysis. Additionally, sugammadex tends to have fewer side effects related to the cardiovascular and gastrointestinal systems, making it a potentially safer option for patients.

What evidence suggests that this trial's treatments could be effective for neuromuscular blockade?

This trial will compare the effectiveness of sugammadex and neostigmine in reversing neuromuscular blockade. Research has shown that sugammadex, administered to participants in one arm of this trial, effectively reverses the muscle relaxation caused by rocuronium during surgeries. Studies have found that sugammadex works faster and has fewer side effects than neostigmine. Specifically, sugammadex significantly reduces the risk of residual muscle weakness and issues like nausea and heart problems. Meanwhile, participants in another arm of this trial will receive neostigmine, which also works but usually takes longer and can cause more side effects. Overall, sugammadex is often chosen for its safety and quick action in reversing muscle relaxation. ^{2 6 7 8 9}

Who Is on the Research Team?

Ryu Komatsu, MD

Principal Investigator

The Cleveland Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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 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 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]

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]

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]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK368317/

SUMMARY OF EVIDENCE - Sugammadex for the Reversal of ... The authors of one SR statistically combined results from 15 RCTs and found that sugammadex significantly reduced drug-related side effects when compared with ...

2. mdpi.com mdpi.com/2077-0383/14/12/4128

Sugammadex for Neuromuscular Blockade Reversal Meta-analyses confirm reduced residual paralysis, nausea/vomiting, and cardiovascular complications with sugammadex versus neostigmine [28,30]. Current evidence ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0007091223005779

Phase III clinical trial comparing the efficacy and safety of ... In summary, adamgammadex (4 mg kg−1) was non-inferior to sugammadex (2 mg kg−1) with respect to the primary and secondary outcomes of the reversal of rocuronium ...

4. nature.com nature.com/articles/s41598-023-48031-6

The arousal effect of sugammadex reversal ... After sugammadex administration, twelve patients with a BIS of 45 − 55 showed clinical signs of awakening but none with a BIS of 25 − 35 (36.4% ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03579589

Study Details | NCT03579589 | The Effect of Sugammadex ... Efficacy and safety of sugammadex compared to neostigmine for reversal of neuromuscular blockade: a meta-analysis of randomized controlled trials. J Clin ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7084040/

Neuromuscular Blockade Agents Reversal with ... The results showed that after sugammadex injection, average time of TOF achieved ≥ 0.7 was 107.57 ± 54.87 seconds; and TOF ≥ 0.9 was 155.29 ± 62.51 seconds. The ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35590273/

an updated meta-analysis of randomized controlled trials ... Analysis of secondary outcomes indicated that administration of sugammadex was associated with less incidence of postoperative nausea and ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2405844025001379

Safety and efficacy of sugammadex in management ... Sugammadex demonstrated rapid and effective reversal of neuromuscular blockades, with ToF recovery times ranging from 79.7 s to 10 min, and short extubation ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT03346057

Safety of Sugammadex for the Reversal of Neuromuscular ... The purpose of this trial is to evaluate the safety of sugammadex for the reversal of neuromuscular blockade (NMB) induced by neuromuscular blockade agents ...