Reversal Agents for Postoperative Urinary Retention

Overseen By Fabio Rodriguez, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: The Cleveland Clinic

Must not be taking: Anticholinergics, Antihistamines, Antidepressants, Antipsychotics

Disqualifiers: Urinary comorbidities, Neurological conditions, 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: 6

Duration: During surgery

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether sugammadex or neostigmine, both muscle relaxant reversal agents, more effectively reverses muscle relaxation effects used during surgery. The focus is on adults undergoing surgery lasting at least two hours and requiring muscle relaxation drugs like rocuronium or vecuronium. Participants should be adults having non-heart-related surgery and planning to use one of these reversal agents. This study could enhance recovery after surgery by reducing urinary problems linked to anesthesia. As a Phase 4 trial, this research involves treatments already FDA-approved and proven effective, seeking to understand how they benefit more patients.

Do I have to stop taking my current medications for this trial?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are currently using anticholinergic medications like antihistamines, phenothiazines, antidepressants, or antipsychotics.

What is the safety track record for these treatments?

Research shows that both neostigmine and sugammadex safely aid muscle recovery after surgery, but they have different effects. Studies have found that neostigmine might make urination more difficult post-surgery. While effective, this issue may occur more frequently than with other treatments. Sugammadex, on the other hand, usually reduces the risk of urination difficulties. Research suggests it significantly lowers this risk compared to neostigmine. Both treatments are generally well-tolerated, but these findings about urination could be important for those considering participation in a clinical trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for postoperative urinary retention because they offer potentially faster and more effective reversal of neuromuscular block. Sugammadex is unique because it directly encapsulates the muscle relaxant molecules, quickly reversing their effects, which is different from the traditional cholinesterase inhibitors like neostigmine that work by increasing acetylcholine levels to counteract the block. Additionally, when neostigmine is paired with glycopyrrolate, it helps to reduce unwanted side effects like bradycardia, making it a more balanced option. These approaches promise quicker recovery and fewer complications for patients after surgery.

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

This trial will compare the effectiveness of sugammadex and neostigmine in reversing neuromuscular block after surgery. Research has shown that both drugs aid recovery from muscle relaxants. Sugammadex, which participants in this trial may receive, significantly reduces the risk of postoperative urinary retention (POUR). Studies also indicate that sugammadex does not affect other recovery aspects, such as the need to return to the hospital. Neostigmine, another treatment option in this trial, has shown mixed results. It can sometimes increase the risk of POUR, although some studies suggest it might help reduce leftover urine in the bladder. Overall, sugammadex appears more effective at managing urinary issues after surgery. ^{1 2 3 5 6}

Who Is on the Research Team?

Kurt Ruetzler, MD

Principal Investigator

The Cleveland Clinic

Are You a Good Fit for This Trial?

This trial is for adults aged 65 or older who are having noncardiac surgery under general anesthesia with muscle relaxation, and will stay in the hospital overnight. They must be healthy enough (ASA status 1-3) and able to consent. People with urinary issues, severe liver or kidney disease, neurological conditions, or those on certain medications can't join.

Inclusion Criteria

I am 65 years old or older.

Informed Consent as documented by signature

I will be given medication to reverse muscle relaxation after surgery.

Exclusion Criteria

I am scheduled to have a urinary catheter placed during surgery.

I will have a catheter placed before surgery.

Presence of a sacral nerve stimulator

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Randomized administration of either neostigmine or sugammadex for reversal of neuromuscular block during surgery

During surgery

1 visit (in-person)

Immediate Postoperative Monitoring

Monitoring of twitch responses and urinary retention in the post anesthesia care unit (PACU)

1 hour after surgery

1 visit (in-person)

Postoperative Follow-up

Monitoring for urinary retention and other outcomes on the regular ward

24 hours after surgery

3 visits (in-person)

Extended Follow-up

Data collection from electronic medical records until postoperative day 4 or discharge

Up to 4 days

What Are the Treatments Tested in This Trial?

Interventions

• Neostigmine
• Neostigmine with glycopyrrolate
• Sugammadex

Trial Overview The study compares two drugs used to reverse muscle relaxation after surgery: Sugammadex and Neostigmine combined with glycopyrrolate. It's a randomized trial for patients given rocuronium or vecuronium during their procedure.

How Is the Trial Designed?

Group I: Neostigmine Active Control 1 Intervention

Reversal of Neuromuscular Block by Neostigmine.

Group II: Sugammadex Active Control 1 Intervention

Reversal of Neuromuscular Block by Sugammadex.

Neostigmine is already approved in United States, European Union, India for the following indications:

Approved in United States as Prostigmin for:

• Myasthenia Gravis
• Reversal of Neuromuscular Blockade
• Urinary Retention

Approved in European Union as Neostigmine for:

• Myasthenia Gravis
• Reversal of Nondepolarizing Muscle Relaxants

Approved in India as Neostigmine for:

• Myasthenia Gravis
• Reversal of Neuromuscular Blockade

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Published Research Related to This Trial

In a study of 485 patients undergoing laparoscopic or robotic hysterectomy, those who received sugammadex had significantly lower odds of experiencing transient postoperative urinary retention (TPOUR) compared to those treated with a combination of glycopyrrolate and neostigmine (GN).

Patients treated with GN were 1.79 times more likely to be discharged with an indwelling catheter, indicating that sugammadex may be a safer option for neuromuscular reversal in this surgical context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of sugammadex on postoperative urinary retention post-laparoscopic and robotic hysterectomy with and without concomitant procedures. Dueñas-Garcia, OF., Shah, T., Fritts, L., et al.[2023]

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 61,898 matched adult inpatients and 95,500 matched adult outpatients, patients who received neostigmine with glycopyrrolate for neuromuscular block reversal experienced a two-fold higher incidence of post-operative urinary retention compared to those reversed with sugammadex (5.0% vs 2.4% inpatients; 0.9% vs 0.4% outpatients).

Multivariable analysis confirmed that using neostigmine was independently associated with a greater risk of post-operative urinary retention, with odds ratios of 2.20 for inpatients and 2.57 for outpatients, indicating a significant safety concern with this reversal method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-operative urinary retention is impacted by neuromuscular block reversal agent choice: A retrospective cohort study in US hospital setting. Bash, LD., Turzhitsky, V., Mark, RJ., et al.[2023]

In a study of 1,974 patients undergoing hysterectomy, the use of sugammadex for reversing neuromuscular blockade was associated with a significantly lower risk of postoperative urinary retention (POUR) compared to neostigmine-glycopyrrolate, with an odds ratio of 0.53.

The findings suggest that the lower risk of POUR with sugammadex may be due to the absence of glycopyrrolate, which is used with neostigmine and may contribute to urinary retention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sugammadex and urinary retention after hysterectomy: A propensity-matched cohort study. De Lima Laporta Miranda, ML., Ochs Kinney, MA., Bakkum-Gamez, JN., et al.[2023]

In a study of 181 patients undergoing unilateral inguinal herniorrhaphy, reversal of neuromuscular blockade with sugammadex was associated with significantly lower rates of postoperative urinary retention (POUR) compared to neostigmine/glycopyrrolate, with only 3% of patients in the sugammadex group experiencing POUR versus 15% in the neostigmine/glycopyrrolate group.

The findings suggest that using sugammadex may be a safer option for preventing POUR, which can lead to complications such as unplanned admissions or emergency room visits, although further confirmation through randomized studies is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urinary Retention Following Inguinal Herniorrhaphy: Role of Neuromuscular Blockade Reversal. Valencia Morales, DJ., Stewart, BR., Heller, SF., et al.[2023]

Glycopyrrolate, commonly used with neostigmine to reverse non-depolarizing neuromuscular blockade, has been associated with adverse effects on the genitourinary system, particularly increasing the risk of urinary retention.

This review aims to update the understanding of glycopyrrolate's impact on post-operative urinary retention, addressing gaps in previous studies that did not prioritize this outcome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycopyrrolate and Post-Operative Urinary Retention: A Narrative Review. Low, J., Escobar, M., Baquero, S., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8899153/

A systematic review and meta-analysis of neostigmine for ... Our results suggested that the neostigmine group had a higher effective rate for urinary retention than the Chinese traditional and physical therapy group (OR = ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0952818023002945

Post-operative urinary retention is impacted by ... This study suggests that neuromuscular block reversal with neostigmine can increase post-operative urinary retention risk.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05794503

Postoperative Urinary Retention After Reversal of ... The count of participants with Postoperative Urinary Retention (POUR) of Sugammadex and Neostigmine Groups is being reported. POUR will be defined as: Inability ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37665083/

Neostigmine for postoperative surgical urine retention The subgroup analysis showed that neostigmine recipients had reduced residual urine volume (mean difference (MD) = -1.16, 95% CI: -2.05--0.27, overall p < 0.05, ...

5. advances.umw.edu.pl advances.umw.edu.pl/pdf/2024/33/5/435.pdf

Neostigmine for postoperative surgical urine retention A total of 14 studies, comprising 4196 participants, were included in the analysis. The primary indicators considered were the effective urinary retention rate, ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38007845/

Post-operative urinary retention is impacted by ... This study suggests that neuromuscular block reversal with neostigmine can increase post-operative urinary retention risk.