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

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

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.

Study Overview

• Status: Completed
• Conditions: Overactive Bladder
• Intervention / Treatment: Drug: Extended Release Tolterodine LA; Drug: Intra Vaginal Estradiol Cream

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Extended Release Tolterodine LA; An anti-muscarinic drug that is used for symptomatic treatment of urinary incontinence.	Drug: Extended Release Tolterodine LA; 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; Other Names: Detrol
Active Comparator: Intra Vaginal Estradiol Cream; For topical application to the vaginal area to treat symptoms of urgency or irritation with urination.	Drug: Intra Vaginal Estradiol Cream; 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.; Other Names: Estrace; Premarin vaginal cream

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: Pfizer
• Investigators: Principal Investigator: Kimberly Gerten, M.D., Park Nicollette, St. Louis, Minnesota; Principal Investigator: Holly E. Richter, Ph.D., M.D., University of Alabama at Birmingham

Publications and helpful links

General Publications

• Ellington DR, Szychowski JM, Malek JM, Gerten KA, Burgio KL, Richter HE. Combined Tolterodine and Vaginal Estradiol Cream for Overactive Bladder Symptoms After Randomized Single-Therapy Treatment. Female Pelvic Med Reconstr Surg. 2016 Jul-Aug;22(4):254-60. doi: 10.1097/SPV.0000000000000256.

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: April 23, 2007
• First Submitted That Met QC Criteria: April 24, 2007
• First Posted (Estimate): April 25, 2007

Study Record Updates

• Last Update Posted (Actual): November 1, 2018
• Last Update Submitted That Met QC Criteria: October 1, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: overactive bladder; incontinence; urinary frequency; urge leakage; nightime urination
• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; 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; Estradiol; Tolterodine Tartrate
• Other Study ID Numbers: F061208008; IIR - DRIVE