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

• ClinicalTrials.gov Identifier: NCT00465894
• Recruitment Status: Completed
• First Posted: April 25, 2007
• Results First Posted: October 23, 2012
• Last Update Posted: November 1, 2018
• Sponsor: University of Alabama at Birmingham
• Collaborator: Pfizer
• Information provided by (Responsible Party): David Rich Ellington, University of Alabama at Birmingham

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Overactive Bladder
• Interventions: Drug: Extended Release Tolterodine LA; Drug: Intra Vaginal Estradiol Cream
• Enrollment: 58

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Group 1: Extended Release Tolterodine	Group 2: Intra Vaginal Estradiol Cream
Arm/Group Description	4 mg Tolterodine po daily for 12 weeks At 12 Weeks, the subjects were offered the addition of the alternative therapy with follow-up at 24 and 52 weeks.	0.5 grams of Intra vaginal estradiol cream nightly for 6 weeks, then twice weekly for 6 weeks. At 12 Weeks, the subjects were offered the addition of the alternative therapy with follow-up at 24 and 52 weeks
Period Title: Treatment For 12 Weeks
Started	30	28
Completed	25	25
Not Completed	5	3
Reason Not Completed
Lost to Follow-up	4	1
Family Issues	1	1
Withdrawal by Subject	0	1
Period Title: Treatment From 12 Weeks To 24 Weeks
Started	14 [1]	14 [1]
Completed	14	14
Not Completed	0	0
[1] We included data only from participants that had complete data sets.
Period Title: Treatment From 24 Weeks to 52 Weeks
Started	11 [1]	14
Completed	11	14
Not Completed	0	0
[1] We included data only from participants that had complete data sets.

Baseline Characteristics

Arm/Group Title		Group 1: Extended Release Tolterodine	Group 2: Intra Vaginal Estradiol Cream	Total
Arm/Group Description		4 mg Tolterodine po daily for 12 weeks	0.5 grams of Intra vaginal estradiol cream nightly for 6 weeks, then twice weekly for 6 weeks	Total of all reporting groups
Overall Number of Baseline Participants		30	28	58
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	30 participants	28 participants	58 participants
		63 (6)	60 (2)	61.5 (4)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants	28 participants	58 participants
	Female	30 100.0%	28 100.0%	58 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Evaluate Subjective Patient Change in Irritative Urinary Symptoms as Measured by the Overactive Bladder Questionnaire (OAB-q) Symptom Bother Score
Description	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.
Time Frame	From baseline through 12 Weeks of Intervention

Outcome Measure Data

Analysis Population Description

A baseline measure was achieved for Group 1 with 30 patients and Group 2 with 28 patients. At the 12 week measurement period, we were unable to analyze 5 patients in Group 1 (leaving 25 patients) and unable to analyze 3 patients in Group 2 (leaving 25 patients). These participants left for reasons identified in the Participant Flow.

Arm/Group Title		Group 1: Extended Release Tolterodine	Group 2: Intravaginal Estradiol Cream
Arm/Group Description:		4 mg Tolterodine po daily for 12 weeks	0.5 grams of Intravaginal estradiol cream nightly for 6 weeks, then twice weekly for 6 weeks
Overall Number of Participants Analyzed		30	28
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	Number Analyzed	30 participants	28 participants
		65.4 (15.3)	61.6 (20.0)
12 Weeks	Number Analyzed	25 participants	25 participants
		46.7 (23.4)	45.4 (21.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: Extended Release Tolterodine, Group 2: Intravaginal Estradiol Cream
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	.45
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

2. Secondary Outcome

Title	Evaluate Subjective Patient Change in Irritative Urinary Symptoms as Measured by the Health Related Quality of Life (HRQL)
Description	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.
Time Frame	From baseline through 12 Weeks of Intervention

Outcome Measure Data

Analysis Population Description

In Group 1, we were unable to analyze 5 patients and in Group 2 we were unable to analyze 3 patients. These participants left for reasons identified in the Participant Flow.

Arm/Group Title		Extended Release Tolterodine	Intravaginal Estradiol Cream
Arm/Group Description:		Tolterodine LA: Tolterodine LA 4 mg once daily for 52 weeks	Estrace Intravaginal Cream: 17-B estradiol cream 0.5 grams nightly for 6 weeks then two times weekly for 46 weeks
Overall Number of Participants Analyzed		30	28
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	Number Analyzed	30 participants	28 participants
		53.1 (22.2)	60.9 (22.5)
12 weeks	Number Analyzed	25 participants	25 participants
		66.0 (26.6)	69.8 (18.2)

3. Secondary Outcome

Title	Evaluate Subjective Patient Change in Irritative Urinary Symptoms
Description	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.
Time Frame	From baseline through 12 Weeks of Intervention

Outcome Measure Data

Analysis Population Description

In Group 1, we were unable to analyze 5 patients and in Group 2 we were unable to analyze 3 patients. These participants left for reasons identified in the Participant Flow.

Arm/Group Title	Group 1: Extended Release Tolterodine	Group 2: Intravaginal Estradiol Cream
Arm/Group Description:	4 mg Tolterodine po daily for 12 weeks	0.5 grams of Intravaginal estradiol cream nightly for 6 weeks, then twice weekly for 6 weeks
Overall Number of Participants Analyzed	25	25
Measure Type: Number; Unit of Measure: participants
Very Much Better	3	0
Much Better	8	7
A Little Better	8	12
No Change	5	5
A Litlle Worse	1	0

4. Secondary Outcome

Title	Subjective Patient Change in Irritative Urinary Symptoms
Description	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.
Time Frame	From baseline through 12 Weeks of Intervention

Outcome Measure Data

Analysis Population Description

In Group 1, we were unable to analyze 5 patients and in Group 2 we were unable to analyze 3 patients. For this outcome ONLY, 1 patient from each Group were not available to obtain the measurements from this questionnaire. Therefore the overall number of participants analyzed for this outcome is less than other outcomes. Please see Participant Flow.

Arm/Group Title	Extended Release Tolterodine LA	Intravaginal Estradiol Cream
Arm/Group Description:	An anti-muscarinic drug that is used for symptomatic treatment of urinary incontinence. Extended Release Tolterodine LA: Tolterodine LA 4 mg once daily for 52 weeks	For topical application to the vaginal area to treat symptoms of urgency or irritation with urination. Intravaginal Estradiol Cream: 17-B estradiol cream 0.5 grams nightly for 6 weeks then two times weekly for 46 weeks
Overall Number of Participants Analyzed	24	24
Measure Type: Number; Unit of Measure: participants
Completely Satisfied	5	3
Somewhat Satisfied	13	13
Not Satisfied	6	8

5. Secondary Outcome

Title	Subjective Patient Change in Irritative Urinary Symptoms As Measured By the 3-Day Voiding Diary
Description	Number of voids and accidents/leakage per 3 day diary. A void is a voluntary and intentional event. An accident is involuntary and unintentional.
Time Frame	From baseline through 12 weeks of Intervention

Outcome Measure Data

Analysis Population Description

25 patients in each group completed voiding diary at baseline. 21 patients completed the voiding diary at 12 weeks in the Tolterodine group (complete diary). 25 patients in the estradiol group completed diary at 12 weeks. Incomplete diaries were not included in our analysis.

Arm/Group Title	Group 1: Extended Release Tolterodine	Group 2: Intravaginal Estradiol Cream
Arm/Group Description:	4 mg Tolterodine po daily for 12 weeks At 12 Weeks, the subjects were offered the addition of the alternative therapy with follow-up at 24 and 52 weeks.	0.5 grams of Intravaginal estradiol cream nightly for 6 weeks, then twice weekly for 6 weeks. At 12 Weeks, the subjects were offered the addition of the alternative therapy with follow-up at 24 and 52 weeks
Overall Number of Participants Analyzed	21	25
Mean (Standard Deviation); Unit of Measure: events
Number of voids	30.4 (11.6)	26.4 (10.5)
Number of voids 12 week follow-up	26.3 (9.7)	24.6 (10.2)
Number of accidents/leakage	10.8 (11.4)	11.9 (10.5)
Number of accidents/leakage at 12 weeks	7.2 (10.6)	7.7 (8.1)

6. Secondary Outcome

Title	Subjective Patient Change in Irritative Urinary Symptoms
Description	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.
Time Frame	Baseline to 24 weeks

Outcome Measure Data

Analysis Population Description

At 24 weeks, only 14 patients from Group 1 & 2 had complete data sets. Those without complete data sets were not included in the analysis.

Arm/Group Title	Group 1: Extended Release Tolterodine + Intravaginal Estradiol	Group 2: Intravaginal Estradiol Cream + Tolterodine
Arm/Group Description:	After 12 weeks of therapy, participants were offered the alternative therapy in addition to their current therapy. They continued with the 4 mg Tolterodine po daily for 12 weeks and added the 0.5 grams intravaginal estradiol twice per week for 24 weeks.	0.5 grams of Intravaginal estradiol cream nightly for 6 weeks, then twice weekly for 6 weeks + 4 mg Tolterodine daily (At 12 Weeks, the subjects were offered the addition of the alternative therapy with follow-up at 24 and 52 weeks.)
Overall Number of Participants Analyzed	14	14
Mean (Standard Deviation); Unit of Measure: units on a scale
	-25.4 (11.6)	-28.7 (20.5)

7. Secondary Outcome

Title	Subjective Patient Change in Irritative Urinary Symptoms
Description	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.
Time Frame	Baseline to 24 weeks

Outcome Measure Data

Analysis Population Description

At 24 weeks, only 14 patients from Group 1 & 2 had complete data sets. Those without complete data sets were not included in the analysis.

Arm/Group Title	Group 1: Extended Release Tolterodine + Intravaginal Estradiol	Group 2: Intravaginal Estradiol Cream + Tolterodine
Arm/Group Description:	After 12 weeks of therapy, participants were offered the alternative therapy in addition to their current therapy . They continued with the 4 mg Tolterodine po daily for 12 weeks and added the 0.5 grams intravaginal estradiol twice per week for 24 weeks.	0.5 grams of Intravaginal estradiol cream nightly for 6 weeks, then twice weekly for 6 weeks + 4 mg Tolterodine daily (At 12 Weeks, the subjects were offered the addition of the alternative therapy with follow-up at 24 and 52 weeks.)
Overall Number of Participants Analyzed	14	14
Mean (Standard Deviation); Unit of Measure: units on a scale
	19.3 (16.8)	20.9 (15.8)

8. Secondary Outcome

Title	Subjective Patient Change in Irritative Urinary Symptoms as Indicated by the Patient Global Impression of Improvement (PGI-I)
Description	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.
Time Frame	Baseline through 24 weeks

Outcome Measure Data

Analysis Population Description

At 24 weeks, only 14 patients from Group 1 & 2 had complete data sets. Those without complete data sets were not included in the analysis.

Arm/Group Title	Group 1: Extended Release Tolterodine + Intravaginal Estradiol	Group 2: Intravaginal Estradiol Cream + Tolterodine
Arm/Group Description:	After 12 weeks of therapy, participants were offered the alternative therapy in addition to their current therapy. They continued with the 4 mg Tolterodine po daily for 12 weeks and added the 0.5 grams intravaginal estradiol twice per week for 24 weeks.	0.5 grams of Intravaginal estradiol cream nightly for 6 weeks, then twice weekly for 6 weeks + 4 mg Tolterodine daily (After 12 weeks of therapy, participants were offered the alternative therapy in addition to their current therapy.)
Overall Number of Participants Analyzed	14	14
Measure Type: Number; Unit of Measure: percentage of participants
	77	77

9. Secondary Outcome

Title	Subjective Patient Change in Irritative Urinary Symptoms as Indicated by the Patient Satisfaction Questionnaire (PSQ)
Description	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.
Time Frame	Baseline through 24 weeks

Outcome Measure Data

Analysis Population Description

At 24 weeks, only 14 patients from Group 1 & 2 had complete data sets. Those without complete data sets were not included in the analysis.

Arm/Group Title	Group 1: Extended Release Tolterodine + Intravaginal Estradiol	Group 2: Intravaginal Estradiol Cream + Tolterodine
Arm/Group Description:	After 12 weeks of therapy, participants were offered the alternative therapy in addition to their current therapy. They continued with the 4 mg Tolterodine po daily for 12 weeks and added the 0.5 grams intravaginal estradiol twice per week for 24 weeks	0.5 grams of Intravaginal estradiol cream nightly for 6 weeks, then twice weekly for 6 weeks+ 4 mg Tolterodine daily (After 12 weeks of therapy, participants were offered the alternative therapy in addition to their current therapy.)
Overall Number of Participants Analyzed	14	14
Measure Type: Number; Unit of Measure: percentage of participants
	88	88

10. Secondary Outcome

Title	Subjective Patient Change in Irritative Urinary Symptoms
Description	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.
Time Frame	Baseline through 52 weeks

Outcome Measure Data

Analysis Population Description

At 52 weeks, only 11 patients in Group 1 and 14 patients from Group 2 had complete data sets. Those without complete data sets were not included in the analysis.

Arm/Group Title	Group 1: Extended Release Tolterodine + Intravaginal Estradiol	Intravaginal Estradiol Cream + Tolterodine
Arm/Group Description:	After 12 weeks of therapy, participants were offered the alternative therapy in addition to their current therapy. They continued with the 4 mg Tolterodine po daily for 12 weeks and added the 0.5 grams intravaginal estradiol twice per week for 52 weeks	Intravaginal estradiol Cream: 17-B estradiol cream 0.5 grams nightly for 6 weeks then two times weekly for 46 weeks+ 4 mg Tolterodine daily At 12 Weeks, the subjects were offered the addition of the alternative therapy with follow-up at 24 and 52 weeks.
Overall Number of Participants Analyzed	11	14
Mean (Standard Deviation); Unit of Measure: units on a scale
	-23.4 (15.6)	-31.3 (24.3)

11. Secondary Outcome

Title	Subjective Patient Change in Irritative Urinary Symptoms
Description	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.
Time Frame	Baseline through 52 weeks

Outcome Measure Data

Analysis Population Description

At 52 weeks, only 11 patients in Group 1 and 14 patients from Group 2 had complete data sets. Those without complete data sets were not included in the analysis.

Arm/Group Title	Group 1: Extended Release Tolterodine + Intravaginal Estradiol	Group 2: Intravaginal Estradiol Cream
Arm/Group Description:	After 12 weeks of therapy, participants were offered the alternative therapy in addition to their current therapy. They continued with the 4 mg Tolterodine po daily for 12 weeks and added the 0.5 grams intravaginal estradiol twice per week for 52 weeks.	0.5 grams of Intravaginal estradiol cream nightly for 6 weeks, then twice weekly for 6 weeks. At 12 Weeks, the subjects were offered the addition of the alternative therapy with follow-up at 24 and 52 weeks
Overall Number of Participants Analyzed	11	14
Mean (Standard Deviation); Unit of Measure: units on a scale
	26.8 (20.5)	19.7 (25.1)

12. Secondary Outcome

Title	Subjective Patient Change in Irritative Symptoms as Indicated by the Patient Global Impression of Improvement (PGI-I)
Description	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.
Time Frame	Baseline through 52 weeks

Outcome Measure Data

Analysis Population Description

At 52 weeks, only 11 patients in Group 1 and 14 patients from Group 2 had complete data sets. Those without complete data sets were not included in the analysis.

Arm/Group Title	Group 1: Extended Release Tolterodine + Intravaginal Estradiol	Group 2: Intravaginal Estradiol Cream
Arm/Group Description:	After 12 weeks of therapy, participants were offered the alternative therapy in addition to their current therapy. They continued with the 4 mg Tolterodine po daily for 12 weeks and added the 0.5 grams intravaginal estradiol twice per week for 52 weeks	0.5 grams of Intra vaginal estradiol cream nightly for 6 weeks, then twice weekly for 6 weeks. At 12 Weeks, the subjects were offered the addition of the alternative therapy with follow-up at 24 and 52 weeks
Overall Number of Participants Analyzed	11	14
Measure Type: Number; Unit of Measure: percentage of participants
	85	85

13. Secondary Outcome

Title	Subjective Patient Change in Irritative Urinary Symptoms as Indicated by the Patient Satisfaction Questionnaire (PSQ)
Description	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.
Time Frame	Baseline through 52 Weeks

Outcome Measure Data

Analysis Population Description

At 52 weeks, only 11 patients in Group 1 and 14 patients from Group 2 had complete data sets. Those without complete data sets were not included in the analysis.

Arm/Group Title	Group 1: Extended Release Tolterodine + Intravaginal Estradiol	Group 2: Intravaginal Estradiol Cream
Arm/Group Description:	After 12 weeks of therapy, participants were offered the alternative therapy in addition to their current therapy. They continued with the 4 mg Tolterodine po daily for 12 weeks and added the 0.5 grams intravaginal estradiol twice per week for 52 weeks.	0.5 grams of Intravaginal estradiol cream nightly for 6 weeks, then twice weekly for 6 weeks. At 12 Weeks, the subjects were offered the addition of the alternative therapy with follow-up at 24 and 52 weeks
Overall Number of Participants Analyzed	11	14
Measure Type: Number; Unit of Measure: percentage of participants
	84	84

Adverse Events

Time Frame	From Baseline through 52 weeks of Intervention
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Group 1: Extended Release Tolterodine		Group 2: Intra Vaginal Estradiol Cream
Arm/Group Description	4 mg Tolterodine po daily for 12-weeks At 12 Weeks, the subjects were offered the addition of the alternative therapy with follow-up at 24 and 52 weeks.		0.5 grams of Intra vaginal estradiol cream nightly for 6 weeks, then twice weekly for 6 weeks At 12 Weeks, the subjects were offered the addition of the alternative therapy with follow-up at 24 and 52 weeks.
All-Cause Mortality
	Group 1: Extended Release Tolterodine		Group 2: Intra Vaginal Estradiol Cream
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/30 (0.00%)		0/28 (0.00%)
Serious Adverse Events
	Group 1: Extended Release Tolterodine		Group 2: Intra Vaginal Estradiol Cream
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0.00%)		0/28 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	1%
	Group 1: Extended Release Tolterodine		Group 2: Intra Vaginal Estradiol Cream
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/30 (56.67%)		6/28 (21.43%)
Gastrointestinal disorders
Constipation †	10/30 (33.33%)	10	0/28 (0.00%)	0
General disorders
xerostomia † [1]	17/30 (56.67%)	17	6/28 (21.43%)	6
† Indicates events were collected by systematic assessment; [1] Xerostomia (also termed dry mouth as a symptom or dry mouth syndrome) is dryness in the mouth (xero- + stom- + -ia), which may be associated with a change in the composition of saliva, or reduced salivary flow, or have no identifiable cause.

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dr. Holly E. Richter
• Organization: University of Alabama at Birmingham
• Phone: 205-934-1704
• EMail: hrichter@uabmc.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: David Rich Ellington, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT00465894
• Other Study ID Numbers: F061208008; IIR - DRIVE
• First Submitted: April 23, 2007
• First Posted: April 25, 2007
• Results First Submitted: June 1, 2012
• Results First Posted: October 23, 2012
• Last Update Posted: November 1, 2018