Sugammadex for Intestinal Obstruction

Overseen By Ryan C Ellis, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Clayton Petro

Must not be taking: Antifungals, HIV protease inhibitors

Disqualifiers: Severe hepatic failure, Severe renal failure, Cancer, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: Surgery day

184 Participants Needed

Trial Summary

What is the purpose of this trial?

The aim of the study is to determine if the usage of sugammadex would reduce the time to return of bowel function when compared to standard of care (neostigmine/glycopyrrolate) when used for neuromuscular blockade reversal in patients with open abdominal wall reconstruction (AWR).

Will I have to stop taking my current medications?

The trial requires that you do not take certain medications that affect liver enzymes, like some antifungals and antibiotics. If you're on these, you might need to stop them to participate.

What data supports the effectiveness of the drug Sugammadex for intestinal obstruction?

Research suggests that Sugammadex, when used to reverse neuromuscular blockade, is associated with improved recovery of bowel function after surgery compared to other drugs like neostigmine/glycopyrrolate. This indicates that Sugammadex may help in restoring bowel movements more effectively, which could be beneficial in treating intestinal obstruction. ^{1 2 3 4 5}

Is sugammadex safe for use in humans?

Sugammadex is generally considered safe for humans, but there are some concerns about allergic reactions and effects on the heart. While these risks are low, ongoing monitoring and research are important. ^{4 6 7 8 9}

How does the drug Sugammadex differ from other treatments for intestinal obstruction?

Sugammadex is unique because it reverses neuromuscular blockade without affecting bowel movements, unlike traditional treatments like neostigmine/glycopyrrolate, which can slow down the intestines. This makes Sugammadex potentially beneficial for quicker recovery of bowel function after surgery. ^{1 3 4 8 10}

Research Team

Clayton C Petro, MD

Principal Investigator

The Cleveland Clinic

Eligibility Criteria

This trial is for adults over 18 needing non-emergency open ventral hernia repair with specific conditions. Eligible participants should not have severe kidney or liver failure, be at risk of small bowel obstruction as judged by the surgeon, use certain drugs affecting liver enzymes, have a history of chronic opioid use, or disorders that compromise the gastrointestinal lining. Pregnant or breastfeeding individuals and those unable to consent are excluded.

Inclusion Criteria

Non-emergent cases

I am over 18 years old.

My hernia's gap is less than 20cm wide.

Exclusion Criteria

I have a known small bowel obstruction at the time of my hernia repair.

I have severe kidney problems.

Pregnant or planning to become pregnant during study period

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either sugammadex or neostigmine/glycopyrrolate for neuromuscular blockade reversal during open abdominal wall reconstruction

Surgery day

1 visit (in-person)

Postoperative Monitoring

Participants are monitored for postoperative bowel function, pain, opioid use, and complications

4 days

Daily monitoring (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including length of hospital stay and nasogastric tube placement

Up to 1 month

Treatment Details

Interventions

• Neostigmine / Glycopyrrolate
• Sugammadex

Trial Overview The study compares sugammadex with standard care (neostigmine/glycopyrrolate) in speeding up the return of bowel function after neuromuscular blockade reversal in abdominal wall reconstruction surgery. It aims to see if sugammadex can improve recovery times for patients undergoing this procedure.

Participant Groups

Group I: Sugammadex Experimental Treatment 1 Intervention

Patients randomized to the experimental arm will receive an IV dose of sugammadex according to the package insert of 2 mg/kg for ≥ 2 twitches, 4 mg/kg for 1-2 post-tetanic twitches

Group II: Neostigmine/Glycopyrrolate Experimental Treatment 1 Intervention

Patients assigned to the control arm receive the standardized reversal neostigmine dose with on-label dosing (0.03-0.07mg/kg) and a fixed ratio of glycopyrrolate

Who Is Running the Clinical Trial?

Clayton Petro

Lead Sponsor

Trials

5

Recruited

1,600+

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Findings from Research

In a study involving 10 healthy patients, the combination of glycopyrrolate and neostigmine significantly reduced the barrier pressure of the lower oesophageal sphincter for up to 20 minutes during gynaecological surgery.

This prolonged reduction in barrier pressure contrasts with previous findings using atropine and neostigmine, where the decrease was temporary and returned to baseline within 5 minutes, suggesting that glycopyrrolate may have a more lasting effect on lower oesophageal sphincter function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the combined effects of glycopyrrolate and neostigmine on the lower oesophageal sphincter. Derrington, MC., Hindocha, N., Smith, G.[2019]

Organ diseases can significantly affect how neuromuscular blocking and reversal drugs work, leading to increased risks of complications like prolonged muscle paralysis and side effects from medications.

Sugammadex has been highlighted as a safer option for reversing neuromuscular block in patients with various organ diseases, showing promising efficacy and safety in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromuscular blocking drugs and their antagonists in patients with organ disease. Craig, RG., Hunter, JM.[2018]

In a study of 102 patients undergoing laparoscopic cholecystectomy, the use of sugammadex for neuromuscular blockade reversal resulted in a significantly faster recovery of gastrointestinal motility, with the first passage of flatus occurring on average 5.82 hours earlier than with pyridostigmine and glycopyrrolate.

While sugammadex improved the time to gas-out, it did not significantly affect the time to first defecation or stool types, indicating its specific benefit in enhancing early postoperative gastrointestinal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromuscular blockade reversal with sugammadex versus pyridostigmine/glycopyrrolate in laparoscopic cholecystectomy: a randomized trial of effects on postoperative gastrointestinal motility. An, J., Noh, H., Kim, E., et al.[2021]

In a study of 731 patients undergoing craniotomy, those who received sugammadex to reverse neuromuscular blockade experienced earlier recovery of bowel function, with a higher likelihood of having their first bowel movement within 24 and 48 hours compared to those treated with neostigmine/glycopyrrolate.

Statistical analyses indicated that sugammadex was associated with improved bowel function recovery, suggesting it may be a more effective option for reversing neuromuscular blockade in terms of postoperative gastrointestinal recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Reversal Technique for Neuromuscular Paralysis on Time to Recovery of Bowel Function after Craniotomy. Deljou, A., Soleimani, J., Sprung, J., et al.[2023]

Sugammadex is more cost-effective than neostigmine or no reversal agent for reversing rocuronium-induced neuromuscular blockade when considering operating room time valued at $8.60/min or more, making it a preferable choice in many scenarios.

The analysis suggests that sugammadex is particularly beneficial for patients at high risk of unplanned postoperative mechanical ventilation (UPMV), but if OR time costs are not factored in, its routine use may not be justified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sugammadex versus neostigmine for routine reversal of rocuronium block in adult patients: A cost analysis. Hurford, WE., Welge, JA., Eckman, MH.[2021]

Sugammadex is an effective agent for quickly reversing neuromuscular block caused by aminosteroidal drugs, offering a faster and more predictable recovery compared to neostigmine, with fewer cholinergic side effects.

Despite its benefits, there are safety concerns regarding potential hypersensitivity reactions and effects on cardiac health, particularly QT interval and clotting times, which require ongoing monitoring and research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of sugammadex for reversal of neuromuscular block. Honing, G., Martini, CH., Bom, A., et al.[2019]

In a review of 10 cases of adverse events associated with sugammadex in Korea, serious reactions included five cases of anaphylaxis and one case of cardiac arrest, highlighting the potential risks of this neuromuscular blockade reverser.

The study found that adverse events often occurred shortly after administration, emphasizing the need for continuous monitoring and caution, especially when higher doses of sugammadex are used without adequate neuromuscular recovery assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of sugammadex that occurred in a Korean population. Han, W., Lee, JM., Park, DH., et al.[2022]

Sugammadex is an effective agent for reversing neuromuscular blockade by encapsulating rocuronium or vecuronium, allowing for rapid recovery even in severe cases, and it has clinical advantages over traditional agents like neostigmine, including fewer side effects such as nausea and pulmonary complications.

While generally safe, there have been reports of anaphylactoid and allergic reactions to sugammadex, highlighting the need for awareness and management strategies for potential hypersensitivity, especially in pediatric cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allergic Reactions to Sugammadex: A Case Series and Review of the Literature. Banoub, R., Alalade, E., Bryant, J., 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 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]

References

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

Evaluation of the combined effects of glycopyrrolate and neostigmine on the lower oesophageal sphincter. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Neuromuscular blocking drugs and their antagonists in patients with organ disease. [2018]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Neuromuscular blockade reversal with sugammadex versus pyridostigmine/glycopyrrolate in laparoscopic cholecystectomy: a randomized trial of effects on postoperative gastrointestinal motility. [2021]

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

Effects of Reversal Technique for Neuromuscular Paralysis on Time to Recovery of Bowel Function after Craniotomy. [2023]

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

Sugammadex versus neostigmine for routine reversal of rocuronium block in adult patients: A cost analysis. [2021]

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

Safety of sugammadex for reversal of neuromuscular block. [2019]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Adverse events of sugammadex that occurred in a Korean population. [2022]

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

Allergic Reactions to Sugammadex: A Case Series and Review of the Literature. [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

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