Efficacy of Combined Pharmacotherapy Versus Solifenacin With Vaginal Estrogen Cream for Women With Detrusor Overactivity

Efficacy and Safety of Solifenacin Combined With Mirabegron Versus Solifenacin With Vaginal Estrogen Cream for the Treatment of Detrusor Overactivity

To investigates the effects of combined pharmacotherapy with solifenacin and mirabegron versus solifenacin with vaginal estrogen cream in women with detrusor overactivity.

Study Overview

• Status: Recruiting
• Conditions: Urinary Bladder, Overactive; Effect of Drug
• Intervention / Treatment: Drug: Solifenacin with vaginal estrogen cream; Drug: Combination pharmacotherapy

Detailed Description

Women with detrusor overactivity who were refractory to anti-muscarinics were enrolled for prospective study. Patients were divided into two groups: one receive combined pharmacotherapy with solifenacin and mirabegron, and the other received solifenacin and vaginal estrogen cream. Incontinence-related symptoms distress and impact on quality of life were evaluated by short form of Urinary Distress Inventory, (UDI-6), Incontinence Impact Questionnaire (IIQ-7) and Overactive Bladder Symptom Score (OABSS). Objective outcomes include changes from baseline in episodes of daily micturition, urgency, urinary incontinence and nocturia.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Hui-Hsuan Lau, MD; Phone Number: +886-2-25433535; Email: huihsuan1220@gmail.com

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Recruiting
    • Mackay Memorial Hospital
    • Contact: Jiun Chyi Hwang, MD; Phone Number: +886-2-2543-3535; Email: jiun1989@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with detrusor overactivity which defined as a urodynamic observation characterized by involuntary detrusor contractions during the filling phase. Those who were refractory to monotherapy with anti-muscarinics were enrolled for prospective study.

Exclusion Criteria:

• Postvoid urine retention before treatment
• Women who had medical illness and contraindication for using solifenacin and mirabegron, such as narrow-angle glaucoma and hypertension
• Concerns for using estrogen include: Women with history of cerebrovascular disease; thromboembolic disorders; gallbladder disease; known or suspected breast carcinoma; estrogen-dependent neoplasm or undiagnosed abnormal genital bleeding.
• Women who were on hormone replacement therapy within 3 months were also excluded from the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Solifenacin with vaginal estrogen cream; Solifenacin 5mg once per day with vaginal conjugated equine estrogen (CEE) 0.625 mg twice a week.	Drug: Solifenacin with vaginal estrogen cream; Solifenacin 5mg with vaginal conjugated equine estrogen (CEE) 0.625 mg; Other Names: Premarin
Active Comparator: Combination pharmacotherapy; Combined solifenacin 5mg and mirabegron 25mg once per day.	Drug: Combination pharmacotherapy; Solifenacin 5mg and Mirabegron 25mg; Other Names: Vesicare and Betmiga

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Short form of Urinary Distress Inventory (UDI-6)	UDI-6 is a valid questionnaire, used particularly to investigate symptoms associated with lower urinary tract dysfunction and inquire on irritative, stress, and obstructive or discomfort complaints. UDI-6 consists of six items: frequent urination; leakage related to feeling of urgency; leakage related to activity, coughing, or sneezing; small amounts of leakage (drops); difficulty emptying the bladder; and pain or discomfort in the lower abdominal or genital area. The total score ranges from 0 to 18 , with a higher score indicating more severe of incontinence.	Assess before treatment and 1 month, 3 months, 6 months and 1 year after treatment
Short form of Incontinence Impact Questionnaire (IIQ-7)	The IIQ-7 assess the impact of urinary incontinence on QoL. 7 items assess influence of urinary incontinence on physical activity, travel, social/relationships & emotional health. Each item is scored between 0 (activities not affected at all) to 3 (activities greatly affected). The total score ranges from 0 to 21, with a higher score indicating more severe of incontinence.	Assess before treatment and 1 month, 3 months, 6 months and 1 year after treatment
Overactive Bladder Symptom Score (OABSS)	The total OABSS is the sum of four symptom scores: daytime frequency (score 0-2), nighttime frequency (score 0-3), urgency (score 0-5), and urgency incontinence (score 0-5). The total score ranges from 0 to 15, with a higher score indicating more severe of OAB symptoms.	Assess before treatment and 1 month, 3 months, 6 months and 1 year after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Episodes of daily micturition	Patients report daily lower urinary tract symptoms episodes	Assess before treatment and 1 month, 3 months, 6 months and 1 year after treatment
Episodes of daily urgency	Patients report daily lower urinary tract symptoms episodes	Assess before treatment and 1 month, 3 months, 6 months and 1 year after treatment
Episodes of daily incontinence	Patients report daily lower urinary tract symptoms episodes	Assess before treatment and 1 month, 3 months, 6 months and 1 year after treatment
Episodes of daily nocturia	Patients report daily lower urinary tract symptoms episodes	Assess before treatment and 1 month, 3 months, 6 months and 1 year after treatment

Collaborators and Investigators

• Sponsor: Mackay Memorial Hospital
• Investigators: Principal Investigator: Hui-Hsuan Lau, MD, Mackay Memorial Hospital

Publications and helpful links

General Publications

• Lightner DJ, Gomelsky A, Souter L, Vasavada SP. Diagnosis and Treatment of Overactive Bladder (Non-Neurogenic) in Adults: AUA/SUFU Guideline Amendment 2019. J Urol. 2019 Sep;202(3):558-563. doi: 10.1097/JU.0000000000000309. Epub 2019 Aug 8.
• Mueller ER, van Maanen R, Chapple C, Abrams P, Herschorn S, Robinson D, Stoelzel M, Yoon SJ, Al-Shukri S, Rechberger T, Gratzke C. Long-term treatment of older patients with overactive bladder using a combination of mirabegron and solifenacin: a prespecified analysis from the randomized, phase III SYNERGY II study. Neurourol Urodyn. 2019 Feb;38(2):779-792. doi: 10.1002/nau.23919. Epub 2019 Jan 15.
• Cardozo L, Lose G, McClish D, Versi E. A systematic review of the effects of estrogens for symptoms suggestive of overactive bladder. Acta Obstet Gynecol Scand. 2004 Oct;83(10):892-7. doi: 10.1111/j.0001-6349.2004.00581.x.

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2022
• Primary Completion (Estimated): June 15, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: December 26, 2023
• First Submitted That Met QC Criteria: December 26, 2023
• First Posted (Actual): January 9, 2024

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 27, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Effectiveness; Estrogens; Detrusor overactivity; Combined pharmacotherapy
• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder, Overactive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Solifenacin Succinate
• Other Study ID Numbers: 22MMHIS039e-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes