Detrol Long Acting (LA) vs Estrace Vaginal Cream for the Treatment of Overactive Bladder Symptoms

Study Overview
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Brief Summary
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The purpose of this study is to determine if long acting tolterodine confers more benefit than intravaginal low dose estrogen in the treatment of Overactive Bladder Syndrome at 12 weeks post-treatment initiation. The hypothesis is that low dose intra-vaginal estrogen confers greater benefit than tolterodine in the treatment of Overactive Bladder symptoms. Secondary outcomes were to assess if the addition of the other therapy to the treatment regimen conferred benefit at 24 weeks and 52 weeks.

Detailed Description
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Lower urinary tract bladder storage symptoms include urinary frequency, urinary urgency, nocturia and urge incontinence. Overactive Bladder (OAB)Syndrome is a condition in which urgency is the predominant symptom with or without urge incontinence and is usually accompanied by frequency and nocturia. The mainstay of treatment of women with OAB syndrome is treatment with anticholinergic medication as well as behavioral therapy. This method of treatment has demonstrated a 60% response rate as reported in the Cochrane Database of Systemic Reviews. In addition to anticholinergic therapy, vaginal atrophy is often corrected as part of a pharmacologic treatment plan. Vaginal atrophy is a condition this is vastly prevalent in post-menopausal women. It is thought to affect up to 48% of post-menopausal women. Many women with this condition experience vaginal dryness, irritation, painful intercourse, as well as urinary symptoms including dysuria, urgency, frequency, nocturia, incontinence and recurrent urinary tract infections. Comparison: Tolterodine LA compared to low dose intra-vaginal estrogen cream for the treatment of OAB symptoms

Official Title
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Randomized Controlled Trial of Tolterodine in Combination With or Without Low-Dose Intravaginal Estradiol Cream for the Treatment of Overactive Bladder in Post-Menopausal Women

Conditions
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Overactive Bladder

Intervention / Treatment
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* Drug: Extended Release Tolterodine LA
* Drug: Intra Vaginal Estradiol Cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Irritative voiding symptoms to include sensory urgency, frequency, urge incontinence, nocturia Postmenopausal women with a prior oophorectomy or 1 year from last menstrual period Women age 40-90 Women with hysterectomy with preserved ovaries must be age 55 or greater or have a documented follicle-stimulating hormone (FSH)>40 to ensure post-menopausal status Community dwelling Ambulatory Ability to participate in a 12 month study Exclusion Criteria: Post-void residual volume>150ml Glaucoma without ophthalmologist clearance Hormone replacement therapy in the past 6 months Current anticholinergic treatment Breast cancer Impaired mental status Undiagnosed vaginal bleeding in the past 12 months Endometrial thickness on pelvic ultrasound >5mm History of thromboembolic event Gynecologic cancer Untreated urinary tract infection (would be eligible after treatment) Stage III pelvic organ prolapse or greater Recent diuretic medication changes (one month from change) Neurologic condition affecting bladder function (Multiple Sclerosis, Parkinsons, spinal cord injury, spina bifida) Congestive heart failure Prior pelvic irradiation Interstitial cystitis

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Extended Release Tolterodine LA<br>An anti-muscarinic drug that is used for symptomatic treatment of urinary incontinence. | Drug: Extended Release Tolterodine LA<br>* Tolterodine LA 4 mg once daily for 52 weeks. At 12 Weeks, the subjects were offered the addition of the alternative therapy with follow-up at 24 and 52 weeks<br>* Other names: Detrol;|
| Active Comparator: Intra Vaginal Estradiol Cream<br>For topical application to the vaginal area to treat symptoms of urgency or irritation with urination. | Drug: Intra Vaginal Estradiol Cream<br>* 17-B estradiol cream 0.5 grams nightly for 6 weeks then two times weekly for 46 weeks. At 12 Weeks, the subjects were offered the addition of the alternative therapy with follow-up at 24 and 52 weeks.<br>* Other names: Premarin vaginal cream;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate Subjective Patient Change in Irritative Urinary Symptoms as Measured by the Overactive Bladder Questionnaire (OAB-q) Symptom Bother Score | The first part of the OAB-q consists of eight questions assessing symptom bother with a possible score from 0 to 100 with a higher score indicating greater symptom bother. | From baseline through 12 Weeks of Intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate Subjective Patient Change in Irritative Urinary Symptoms as Measured by the Health Related Quality of Life (HRQL) | Assessment made using the Health Related Quality of Life (HRQL) portion of the OAB-q. The second part of the OAB-q, the HRQL consists of 25 questions that assesses HRQL which addresses coping, concern, sleep and social interaction where the scoring scale is from 0 to 100 with a higher score indicating a better quality of life. | From baseline through 12 Weeks of Intervention | 
| Evaluate Subjective Patient Change in Irritative Urinary Symptoms | Assessment measured using the Patient Global Impression of Improvement (PGI-I), patient perception of improvement. The PGI-I is a transition scale that is a single question asking the patient to rate their urinary tract condition now, as compared with how it was prior to before beginning treatment on a scale from 1 being very much better to 7 being very much worse. Frequencies of each response was reported. Each level achieved (movement towards 1), is considered an improvement. | From baseline through 12 Weeks of Intervention | 
| Subjective Patient Change in Irritative Urinary Symptoms | This was measured using the Patient Satisfaction Questionnaire (PSQ). The PSQ consists of a single question, How satisfied are you with your progress since your treatment in which the 3 possible responses are completely satisfied, somewhat satisfied, and not satisfied. The goal of treatment was to move all participants to completely satisfied. | From baseline through 12 Weeks of Intervention | 
| Subjective Patient Change in Irritative Urinary Symptoms As Measured By the 3-Day Voiding Diary | Number of voids and accidents/leakage per 3 day diary. A void is a voluntary and intentional event. An accident is involuntary and unintentional. | From baseline through 12 weeks of Intervention | 
| Subjective Patient Change in Irritative Urinary Symptoms | The first part of the OAB-q consists of eight questions assessing symptom bother with a possible score from 0 to 100 with a higher score indicating greater symptom bother. | Baseline to 24 weeks | 
| Subjective Patient Change in Irritative Urinary Symptoms | Assessment made using the Health Related Quality of Life (HRQL) portion of the OAB-q. The second part of the OAB-q, the HRQL consists of 25 questions that assesses HRQL which addresses coping, concern, sleep and social interaction where the scoring scale is from 0 to 100 with a higher score indicating a better quality of life. | Baseline to 24 weeks | 
| Subjective Patient Change in Irritative Urinary Symptoms as Indicated by the Patient Global Impression of Improvement (PGI-I) | Assessment measured using the Patient Global Impression of Improvement (PGI-I), patient perception of improvement. The PGI-I is a transition scale that is a single question asking the patient to rate their urinary tract condition now, as compared with how it was prior to before beginning treatment on a scale from 1 being very much better to 7 being very much worse. Each level achieved(movement towards 1), is considered an improvement. | Baseline through 24 weeks | 
| Subjective Patient Change in Irritative Urinary Symptoms as Indicated by the Patient Satisfaction Questionnaire (PSQ) | As measured by the Patient Satisfaction Questionnaire (PSQ). The PSQ consists of a single question, How satisfied are you with your progress since your treatment in which the 3 possible responses are completely satisfied, somewhat satisfied, and not satisfied. The goal of treatment was to move all participants to completely satisfied. | Baseline through 24 weeks | 
| Subjective Patient Change in Irritative Urinary Symptoms | The first part of the OAB-q consists of eight questions assessing symptom bother with a possible score from 0 to 100 with a higher score indicating greater symptom bother. | Baseline through 52 weeks | 
| Subjective Patient Change in Irritative Urinary Symptoms | Assessment made using the Health Related Quality of Life (HRQL) portion of the OAB-q. The second part of the OAB-q, the HRQL consists of 25 questions that assesses HRQL which addresses coping, concern, sleep and social interaction where the scoring scale is from 0 to 100 with a higher score indicating a better quality of life. | Baseline through 52 weeks | 
| Subjective Patient Change in Irritative Symptoms as Indicated by the Patient Global Impression of Improvement (PGI-I) | Assessment measured using the Patient Global Impression of Improvement (PGI-I), patient perception of improvement. The PGI-I is a transition scale that is a single question asking the patient to rate their urinary tract condition now, as compared with how it was prior to before beginning treatment on a scale from 1 being very much better to 7 being very much worse. Each level achieved(movement towards 1), is considered an improvement. | Baseline through 52 weeks | 
| Subjective Patient Change in Irritative Urinary Symptoms as Indicated by the Patient Satisfaction Questionnaire (PSQ) | As measured by the Patient Satisfaction Questionnaire (PSQ).The PSQ consists of a single question, How satisfied are you with your progress since your treatment in which the 3 possible responses are completely satisfied, somewhat satisfied, and not satisfied. The goal of treatment was to move all participants to completely satisfied. | Baseline through 52 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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overactive bladder, urge leakage, nightime urination, incontinence, urinary frequency