Tizanidine for Urinary Retention

Overseen By Jungeun Lee, MS

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: NorthShore University HealthSystem

Disqualifiers: Age <18, Colorectal surgery, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Postoperative urinary retention has been defined as the inability to void despite having fluid in the bladder during the postoperative period. Urinary retention after pelvic reconstructive surgery requiring indwelling catheter or self-catheterization usage occurs in approximately 30-60% of patients postoperatively. Our prior retrospective chart review reviewing postoperative urinary retention rates after pelvic reconstructive surgery demonstrated postoperative urinary retention after a sacrospinous vaginal vault suspension to be approximately 78.9%. Many women consider being discharged home with a Foley catheter to be a surgical complication and describe catheter use as the worst aspect of their surgery. Indwelling catheters are the leading cause of hospital-acquired urinary tract infections (UTIs), are often a source of embarrassment and inconvenience for patients, and often require additional office visits and healthcare utilization. Tizanidine is a muscle relaxant which can work to alleviate this spasm and, theoretically, prevent postoperative urinary retention. Tizanidine also works as an alpha-adrenergic receptor blocker which can increase smooth muscle relaxation around the urethra specifically and, theoretically, improve urine flow. Postoperative urinary retention is extremely common after pelvic reconstructive surgery involving a sacrospinous vaginal vault suspension and is extremely bothersome to patients. Tizanidine is a low-risk, well tolerated, cost-effective medication. No study to date has evaluated preoperative administration of tizanidine for postoperative urinary retention.

Will I have to stop taking my current medications?

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

Is Tizanidine safe for humans?

A study on children with urinary issues found that Tizanidine was generally well-tolerated, meaning it didn't cause many side effects. This suggests it is generally safe for humans, but always consult with a healthcare provider for personal medical advice. ^{1 2 3 4 5}

How does the drug Tizanidine differ from other treatments for urinary retention?

Tizanidine is unique because it is primarily a muscle relaxant used for conditions like muscle spasticity, and its use for urinary retention is novel, as there are no standard treatments specifically targeting this condition. This drug may work differently by potentially relaxing the bladder muscles, which is not the typical approach for treating urinary retention. ^{6 7 8 9 10}

Research Team

Angela L Leffelman, MD

Principal Investigator

Endeavor Health

Eligibility Criteria

This trial is for women who have had a specific pelvic reconstructive surgery called sacrospinous ligament suspension. It's not open to those who haven't had this procedure.

Inclusion Criteria

I have had a procedure to support my pelvic organs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative

Tizanidine 2mg is administered preoperatively prior to scheduled sacrospinous ligament suspension

1 day

1 visit (in-person)

Immediate Postoperative

Immediate postoperative evaluation for urinary retention and pain management

1 day

1 visit (in-person)

Follow-up

Participants are monitored for unplanned admissions, office visits, or encounters within 30 days after surgery

30 days

Treatment Details

Interventions

• Tizanidine

Trial Overview The study tests if Tizanidine, a muscle relaxant and alpha-adrenergic blocker, can prevent urinary retention—a common issue where patients can't pee after the surgery mentioned above.

Participant Groups

Group I: Tizanidine Experimental Treatment 1 Intervention

Tizanidine 2mg will be given preoperatively prior to scheduled sacrospinous ligament suspension

Tizanidine is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Zanaflex for:

• Muscle spasticity

Approved in European Union as Zanaflex for:

• Muscle spasticity

Approved in Canada as Zanaflex for:

• Muscle spasticity

Approved in Japan as Zanaflex for:

• Muscle spasticity

Who Is Running the Clinical Trial?

NorthShore University HealthSystem

Lead Sponsor

Trials

134

Recruited

740,000+

Endeavor Health

Lead Sponsor

Trials

135

Recruited

742,000+

Findings from Research

Tolterodine, a muscarinic receptor antagonist, is the gold standard for treating storage lower urinary tract symptoms (LUTS) in men, offering a better efficacy and adverse event profile compared to earlier antimuscarinics, which often caused issues like dry mouth and cognitive dysfunction.

The extended release (ER) formulation of tolterodine (4 mg once daily) is as effective as the intermediate release (IR) formulation (2 mg twice daily) but has fewer side effects, and combining tolterodine with an alpha-blocker significantly improves treatment efficacy without increasing the risk of acute urinary retention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolterodine in the Treatment of Male LUTS. Gacci, M., Sebastianelli, A., Salvi, M., et al.[2018]

Long-term use of terazosin, an alpha-blocker, in two children with Hinman's syndrome showed no significant side effects, indicating its safety for treating non-neurogenic bladder dysfunction.

Both children experienced improvement in urgency symptoms and resolution of secondary enuresis, suggesting that terazosin, combined with other therapies, can effectively manage bladder dysfunction and may have lasting benefits even after treatment is stopped.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use and rationale of selective alpha blockade in children with non-neurogenic neurogenic bladder dysfunction. Bogaert, G., Beckers, G., Lombaerts, R.[2019]

In a study of 100 women aged 20 to 70 with lower urinary tract symptoms, terazosin was found to be significantly more effective than placebo, with 80% of terazosin users achieving a quality of life score of 2 or less compared to 55% of placebo users.

Terazosin also led to significant improvements in specific symptoms like frequency and straining, and while there were some adverse events, they were not significantly different from those experienced by the placebo group, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Terazosin therapy for patients with female lower urinary tract symptoms: a randomized, double-blind, placebo controlled trial. Low, BY., Liong, ML., Yuen, KH., et al.[2013]

In a study of 40 children with dysfunctional voiding, tizanidine demonstrated significant improvements in nocturnal enuresis, urgency attacks, and daytime incontinence compared to baseline, indicating its efficacy as a treatment option.

Both tizanidine and doxazosin showed similar overall improvements in symptoms, but tizanidine had a better profile for reducing specific voiding issues, with a low incidence of adverse effects (15% overall), suggesting it is a safe treatment for children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doxazosin versus tizanidine for treatment of dysfunctional voiding in children: a prospective randomized open-labeled trial. El-Hefnawy, AS., Helmy, T., El-Assmy, MM., et al.[2014]

In a study of 60 men over 50 years old with acute urinary retention (AUR) due to benign prostatic hyperplasia (BPH), silodosin significantly improved the success rate of trial without catheter (TWOC) to 76.7%, compared to 36.7% in the placebo group.

Silodosin was found to be safe, with no reported adverse effects, and it reduced the odds of TWOC failure, indicating its efficacy in managing AUR related to BPH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective randomized placebo-controlled study to assess the safety and efficacy of silodosin in the management of acute urinary retention. Kumar, S., Tiwari, DP., Ganesamoni, R., et al.[2022]

A 57-year-old immunosuppressed male developed urinary retention after a shingles outbreak, highlighting a rare complication of herpes zoster linked to viral infection in the sacral area.

After receiving antiviral and corticosteroid treatment, the patient fully recovered bladder function within 6 weeks, indicating that timely medical intervention can effectively address this complication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Herpes-zoster associated urinary retention in a 57-year-old immunocompromised male. Au, VH., Kazi, A., Bruha, M., et al.[2020]

A case of complete urinary retention was linked to a herpes zoster virus (HZV) neurogenic bladder, highlighting a rare but significant complication of HZV infection.

The study discusses various aspects of the disease, including urodynamics and the underlying physiological mechanisms, which are important for understanding how HZV can affect bladder function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Complete urinary retention secondary to lumbosacral zona]. Punga, A., Zemrag, J., Galas, JM., et al.[2006]

Two cases of acute urinary retention in Chinese patients were linked to reactivation of sacral herpes zoster, highlighting a rare complication of this viral infection.

Treatment involved indwelling urinary catheterization, antiviral medication (ganciclovir), and physiotherapy with infrared light, which successfully restored the micturition reflex in both patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Herpes zoster-induced acute urinary retention: Two cases and literature review. He, H., Tang, C., Yi, X., et al.[2018]

Atropa belladonna L. and its active compound atropine were found to induce urinary retention in rats, indicating a significant pharmacological effect.

The study suggests that Atropa belladonna is more effective in causing urinary retention than previously anticipated based on its alkaloid content, highlighting the need for further investigation into its mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative study of Atropa belladonna and atropine on an animal model of urinary retention. Tita, B., Bolle, P., Martinoli, L., et al.[2019]

A case report of a 26-year-old man revealed that acute urinary retention can occur after brief methamphetamine use, highlighting the need for awareness of drug-related causes in younger patients presenting with urinary issues.

The patient experienced significant improvement after catheterization and discontinuation of methamphetamine, suggesting that addressing drug use is crucial in managing urinary retention effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urinary retention concomitant with methamphetamine use: a case report. Ojo, AO., Ajasa, AL., Oladipupo, RB., et al.[2021]

References

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

Tolterodine in the Treatment of Male LUTS. [2018]

2. Brazil pubmed.ncbi.nlm.nih.gov

The use and rationale of selective alpha blockade in children with non-neurogenic neurogenic bladder dysfunction. [2019]

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

Terazosin therapy for patients with female lower urinary tract symptoms: a randomized, double-blind, placebo controlled trial. [2013]

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

Doxazosin versus tizanidine for treatment of dysfunctional voiding in children: a prospective randomized open-labeled trial. [2014]

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

Prospective randomized placebo-controlled study to assess the safety and efficacy of silodosin in the management of acute urinary retention. [2022]

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

Herpes-zoster associated urinary retention in a 57-year-old immunocompromised male. [2020]

7. France pubmed.ncbi.nlm.nih.gov

[Complete urinary retention secondary to lumbosacral zona]. [2006]

8. India pubmed.ncbi.nlm.nih.gov

Herpes zoster-induced acute urinary retention: Two cases and literature review. [2018]

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

A comparative study of Atropa belladonna and atropine on an animal model of urinary retention. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Urinary retention concomitant with methamphetamine use: a case report. [2021]