Behavior Enhances Drug Reduction of Incontinence (BE-DRI)

• Sponsor: HealthCore-NERI (Other)
• Overall Status: Completed
• CT.gov ID: NCT00090584
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 307
• Locations: 9
• Arms: 2
• Duration (Months): 24
• Patients Per Site: 34.1
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The primary aim of this study is to test if the addition of behavioral treatment to drug therapy for the treatment of urge incontinence will increase the number of patients who can discontinue drug therapy and sustain a significant reduction of incontinence.

Condition or Disease	Intervention/Treatment	Phase
Urinary Incontinence (UI)	Drug: Tolterodine; Behavioral: Behavioral training	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 307 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Behavior Enhances Drug Reduction of Incontinence
• Study Start Date: Aug 1, 2004
• Actual Primary Completion Date: Dec 1, 2005
• Actual Study Completion Date: Aug 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Combination therapy Women randomly assigned to this condition receive 10 weeks of anti-cholinergic medication (tolterodine) and behavioral training.	Drug: Tolterodine; 4mg/d for 10 weeks. Could be reduced to 2mg/d for managing side effects.; Behavioral: Behavioral training; Training in pelvic floor muscle control and exercises; behavioral strategies to diminish urgency, suppress bladder contractions and prevent incontinence; delayed voiding; and individualized fluid management.
Active Comparator: Drug therapy alone Women assigned to this arm received 10 weeks of anti-cholinergic medication (tolterodine), only.	Drug: Tolterodine; 4mg/d for 10 weeks. Could be reduced to 2mg/d for managing side effects.

Outcome Measures

Primary Outcome Measures

1. Proportion of Women Who Meet Definition of Success [8 months]

   Proportion of women who meet definition of success: not taking drug or receiving other urge UI therapy (i.e., neuromodulation, botox injections, myomectomy, electrical stimulation, or any intravesical therapy) and not taking a tricyclic antidepressant or duloxetine at 8 months; and a >70% reduction in number of incontinence episodes as compared to baseline.

Secondary Outcome Measures

1. Change in Incontinence Episodes [Baseline and 10 weeks]

   Change from baseline to 10 weeks in number of incontinence episodes per week as reported on bladder diary.

2. Change in Voids Per Day [baseline and 10 weeks]

   Change from baseline to 10 weeks in frequency of voids per day as reported on bladder diary

3. Symptom Distress [baseline, 10 weeks and 8 months]

   Urogenital distress inventory (UDI). Higher score indicates greater distress. Possible range 0 to 300.

4. Symptom Bother [baseline, 10 weeks and 8 months]

   Disease specific overactive bladder scale (OAB-q). HIgher score indicates greater bother. Possible range 0 to 100.

5. Satisfaction [10 weeks]

   Number of women who responded "completely satisfied" to question, "How satisfied are you with your progress?"

6. Satisfaction [8 months]

   Number of women who responded "completely satisfied" to question "How satisfied are you with your progress?"

7. Symptom Improvement [10 weeks]

   Number of women who responded "much better" or "better" to question: "Overall, do you feel that you are much better, better, about the same, worse or much worse?"

8. Symptom Improvement [8 months]

   Number of women who responded "much better" or "better" to question: "Overall, do you feel that you are much better, better, about the same, worse or much worse?"

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion:

• Female

• Urge predominant incontinence

• Incontinent > 3 mos

• Available for 8 mos of followup

Exclusion:

• Pregnancy or < 6 mos post-partum

• Hypersensitivity to drug (tolterodine)

• Systemic disease that affects bladder function (e.g., Parkinson's disease, Multiple Sclerosis, spinal cord injury)

• History of extensive behavior treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35233
2	University of California	San Diego	California	United States	92103
3	Loyola University Medical Center	Maywood	Illinois	United States	60153
4	University of Maryland	Baltimore	Maryland	United States	21201
5	Oakwood Hospital and Medical Center	Royal Oak	Michigan	United States	48123
6	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
7	University of Texas Southwestern	Dallas	Texas	United States	75390
8	University of Texas Health Sciences Center	San Antonio	Texas	United States	78229
9	University of Utah	Salt Lake City	Utah	United States	84132

Sponsors and Collaborators

• HealthCore-NERI
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Study Chair: William D Steers, M.D., University of Virginia

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• www.uitn.net

Publications

• Borello-France D, Burgio KL, Goode PS, Markland AD, Kenton K, Balasubramanyam A, Stoddard AM; Urinary Incontinence Treatment Network. Adherence to behavioral interventions for urge incontinence when combined with drug therapy: adherence rates, barriers, and predictors. Phys Ther. 2010 Oct;90(10):1493-505. doi: 10.2522/ptj.20080387. Epub 2010 Jul 29.
• Brubaker L, Lukacz ES, Burgio K, Zimmern P, Norton P, Leng W, Johnson H, Kraus S, Stoddard A. Mixed incontinence: comparing definitions in non-surgical patients. Neurourol Urodyn. 2011 Jan;30(1):47-51. doi: 10.1002/nau.20922.
• Burgio KL, Kraus SR, Borello-France D, Chai TC, Kenton K, Goode PS, Xu Y, Kusek JW; Urinary Incontinence Treatment Network. The effects of drug and behavior therapy on urgency and voiding frequency. Int Urogynecol J. 2010 Jun;21(6):711-9. doi: 10.1007/s00192-010-1100-x. Epub 2010 Feb 9.
• Burgio KL, Kraus SR, Menefee S, Borello-France D, Corton M, Johnson HW, Mallett V, Norton P, FitzGerald MP, Dandreo KJ, Richter HE, Rozanski T, Albo M, Zyczynski HM, Lemack GE, Chai TC, Khandwala S, Baker J, Brubaker L, Stoddard AM, Goode PS, Nielsen-Omeis B, Nager CW, Kenton K, Tennstedt SL, Kusek JW, Chang TD, Nyberg LM, Steers W; Urinary Incontinence Treatment Network. Behavioral therapy to enable women with urge incontinence to discontinue drug treatment: a randomized trial. Ann Intern Med. 2008 Aug 5;149(3):161-9.
• Dyer KY, Xu Y, Brubaker L, Nygaard I, Markland A, Rahn D, Chai TC, Stoddard A, Lukacz E; Urinary Incontinence Treatment Network (UITN). Minimum important difference for validated instruments in women with urge incontinence. Neurourol Urodyn. 2011 Sep;30(7):1319-24. doi: 10.1002/nau.21028. Epub 2011 May 11.
• Fitzgerald MP, Dubeau CE, Kraus SR, Johnson HW Jr, Rahn DD, Mallett V, Stoddard AM, Zyczynski HM; Urinary Incontinence Treatment Network. Patient expectations did not predict outcome of drug and behavioral treatment of urgency urinary incontinence. Female Pelvic Med Reconstr Surg. 2011 Sep;17(5):231-7.
• Fitzgerald MP, Lemack G, Wheeler T, Litman HJ; Urinary Incontinence Treatment Network. Nocturia, nocturnal incontinence prevalence, and response to anticholinergic and behavioral therapy. Int Urogynecol J Pelvic Floor Dysfunct. 2008 Nov;19(11):1545-50. doi: 10.1007/s00192-008-0687-7. Epub 2008 Aug 14.
• Goode PS, Burgio KL, Kraus SR, Kenton K, Litman HJ, Richter HE; Urinary Incontinence Treatment Network. Correlates and predictors of patient satisfaction with drug therapy and combined drug therapy and behavioral training for urgency urinary incontinence in women. Int Urogynecol J. 2011 Mar;22(3):327-34. doi: 10.1007/s00192-010-1287-x. Epub 2010 Oct 13.
• Markland AD, Richter HE, Kenton KS, Wai C, Nager CW, Kraus SR, Xu Y, Tennstedt SL; Urinary Incontinence Treatment Network. Associated factors and the impact of fecal incontinence in women with urge urinary incontinence: from the Urinary Incontinence Treatment Network's Behavior Enhances Drug Reduction of Incontinence study. Am J Obstet Gynecol. 2009 Apr;200(4):424.e1-8. doi: 10.1016/j.ajog.2008.11.023. Epub 2009 Feb 6.
• Richter HE, Burgio KL, Chai TC, Kraus SR, Xu Y, Nyberg L, Brubaker L. Predictors of outcomes in the treatment of urge urinary incontinence in women. Int Urogynecol J Pelvic Floor Dysfunct. 2009 May;20(5):489-97. doi: 10.1007/s00192-009-0805-1. Epub 2009 Jan 30.
• Urinary Incontinence Treatment Network (UITN). Design of the Behavior Enhances Drug Reduction of Incontinence (BE-DRI) study. Contemp Clin Trials. 2007 Jan;28(1):48-58. Epub 2006 Jun 18.
• Zimmern P, Litman HJ, Mueller E, Norton P, Goode P; Urinary Incontinence Treatment Network. Effect of fluid management on fluid intake and urge incontinence in a trial for overactive bladder in women. BJU Int. 2010 Jun;105(12):1680-5. doi: 10.1111/j.1464-410X.2009.09055.x. Epub 2009 Nov 13.

• Responsible Party: HealthCore-NERI
• ClinicalTrials.gov Identifier: NCT00090584
• Other Study ID Numbers: BE-DRI (completed)
• First Posted: Aug 31, 2004
• Last Update Posted: Jun 17, 2013
• Last Verified: May 1, 2013

• Keywords provided by HealthCore-NERI: Urge urinary incontinence (UUI); Drug/Behavior treatment
• Additional relevant MeSH terms: Urinary Incontinence; Enuresis; Tolterodine Tartrate

Study Results

Participant Flow

Recruitment Details	Between July, 2004 and January, 2006 4,043 women were screened for eligibility and 561 provided written consent. After further screening, 134 were found to be ineligible, 119 withdrew consent and 1 was excluded erroneously. The remaining 307 were randomized to one of the treatment arms.
Pre-assignment Detail	Of the 134 found to be ineligible after consent, for 77 their urinary incontinence (UI) was not urge predominant, 19 had fewer than 7 episodes of incontinence per week and the other 38 were excluded for a variety of reasons.

Arm/Group Title	Combination Therapy	Drug Therapy Alone
Arm/Group Description	Women randomly assigned to this condition receive 10 weeks of anti-cholinergic medication and behavioral training.	Women assigned to this arm received 10 weeks of anti-cholinergic medication, only.
Period Title: Baseline to 10 Weeks
STARTED	154	153
COMPLETED	139	141
NOT COMPLETED	15	12
Period Title: Baseline to 10 Weeks
STARTED	154	153
COMPLETED	110	112
NOT COMPLETED	44	41

Baseline Characteristics

Arm/Group Title	Combination Therapy	Drug Therapy Alone	Total
Arm/Group Description	Women randomly assigned to this condition receive 10 weeks of anti-cholinergic medication and behavioral training.	Women assigned to this arm received 10 weeks of anti-cholinergic medication, only.	Total of all reporting groups
Overall Participants	154	153	307
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	112 72.7%	106 69.3%	218 71%
>=65 years	42 27.3%	47 30.7%	89 29%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.8 (14.2)	58.0 (13.5)	56.9 (13.9)
Sex: Female, Male (Count of Participants)
Female	154 100%	153 100%	307 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	154 100%	153 100%	307 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Women Who Meet Definition of Success
Description	Proportion of women who meet definition of success: not taking drug or receiving other urge UI therapy (i.e., neuromodulation, botox injections, myomectomy, electrical stimulation, or any intravesical therapy) and not taking a tricyclic antidepressant or duloxetine at 8 months; and a >70% reduction in number of incontinence episodes as compared to baseline.
Time Frame	8 months

Outcome Measure Data

Analysis Population Description

All women who completed the 8 months assessment or were known to return to drug use prior to that time.

Arm/Group Title	Combination Therapy	Drug Therapy Alone
Arm/Group Description	Women randomly assigned to this condition receive 10 weeks of anti-cholinergic medication and behavioral training.	Women assigned to this arm received 10 weeks of anti-cholinergic medication, only.
Measure Participants	118	119
Number [participants]	43 27.9%	41 26.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Combination Therapy, Drug Therapy Alone
	Comments	Kaplan Meier Lifetable analysis was used to compute the 8 month cumulative success rates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.74
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Difference in cumulative success rates
	Estimated Value	0
	Confidence Interval	(2-Sided) 95%; -0.12 to 0.12
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.06
	Estimation Comments

2. Secondary Outcome

Title	Change in Incontinence Episodes
Description	Change from baseline to 10 weeks in number of incontinence episodes per week as reported on bladder diary.
Time Frame	Baseline and 10 weeks

Outcome Measure Data

Analysis Population Description

All women with valid bladder diary at baseline and 10 weeks in each treatment group.

Arm/Group Title	Combination Therapy	Drug Therapy Alone
Arm/Group Description	Women randomly assigned to this condition receive 10 weeks of anti-cholinergic medication and behavioral training.	Women assigned to this arm received 10 weeks of anti-cholinergic medication, only.
Measure Participants	133	136
Mean (Standard Error) [incontinence episodes per week]	-20.4 (1.4)	-18.5 (1.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Combination Therapy, Drug Therapy Alone
	Comments	Test of hypothesis of no difference in change in episodes between the two groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.34
	Comments	Mixed effect repeated measures analysis of variance controlling for study site.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.9
	Confidence Interval	(2-Sided) 95%; -2.0 to 5.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.0
	Estimation Comments

3. Secondary Outcome

Title	Change in Voids Per Day
Description	Change from baseline to 10 weeks in frequency of voids per day as reported on bladder diary
Time Frame	baseline and 10 weeks

Outcome Measure Data

Analysis Population Description

All women with valid bladder diary at baseline and 10 weeks in each treatment group.

Arm/Group Title	Combination Therapy	Drug Therapy Alone
Arm/Group Description	Women randomly assigned to this condition receive 10 weeks of anti-cholinergic medication and behavioral training.	Women assigned to this arm received 10 weeks of anti-cholinergic medication, only.
Measure Participants	133	136
Mean (Standard Error) [voids per day]	-0.5 (0.4)	0.3 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Combination Therapy, Drug Therapy Alone
	Comments	Null hypothesis of no difference between arms in change in number of voids per day from baseline to 10 weeks.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.08
	Comments	Repeated measures ANOVA controlling for clinical site.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -1.7 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.5
	Estimation Comments	Difference (group 1 - group 2) in change from baseline to follow-up in voids per day.

4. Secondary Outcome

Title	Symptom Distress
Description	Urogenital distress inventory (UDI). Higher score indicates greater distress. Possible range 0 to 300.
Time Frame	baseline, 10 weeks and 8 months

Outcome Measure Data

Analysis Population Description

All women who completed UDI at each time in each treatment group

Arm/Group Title	Combination at Baseline	Combination at 10 Weeks	Combiniation at 8 Months	Drug Only at Baseline	Drug Only at 10 Weeks	Drug Only at 8 Months
Arm/Group Description	Baseline value for women in combination therapy	10 week value for women in combination arm	8 months value from women in combination arm	Baseline value for women randomized to drug only	10 week value for women randomized to drug only	8 month value for women randomized to drug only
Measure Participants	154	133	109	153	136	111
Mean (Standard Deviation) [units on a scale]	121.4 (3.8)	47.3 (4.1)	61.9 (4.3)	118.2 (3.9)	58.1 (4.0)	83.3 (4.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Combination Therapy, Drug Therapy Alone, Combiniation at 8 Months, Drug Only at Baseline, Drug Only at 10 Weeks, Drug Only at 8 Months
	Comments	Null hypothesis is that there is no difference between treatment groups in improvement in UDI over time
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments	Repeated measures ANOVA
	Method	Mixed Models Analysis
	Comments	Main hypothesis tested by F-test for treatment by time interaction (2 and 509 degrees of freedom). No parameters estimated.
Method of Estimation	Estimation Parameter	Other
	Estimated Value	0
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Symptom Bother
Description	Disease specific overactive bladder scale (OAB-q). HIgher score indicates greater bother. Possible range 0 to 100.
Time Frame	baseline, 10 weeks and 8 months

Outcome Measure Data

Analysis Population Description

Participants who completed OAB-q assessment at each time in each treatment group.

Arm/Group Title	Combination at Baseline	Combination at 10 Weeks	Combiniation at 8 Months	Drug Only at Baseline	Drug Only at 10 Weeks	Drug Only at 8 Months
Arm/Group Description	Baseline value for women in combination therapy	10 week value for women in combination arm	8 months value from women in combination arm	Baseline value for women randomized to drug only	10 week value for women randomized to drug only	8 month value for women randomized to drug only
Measure Participants	154	133	109	153	136	111
Mean (Standard Deviation) [units on a scale]	59.9 (1.7)	23.1 (1.8)	29.0 (1.9)	60.0 (1.7)	29.6 (1.7)	39.6 (1.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Combination Therapy, Drug Therapy Alone, Combiniation at 8 Months, Drug Only at Baseline, Drug Only at 10 Weeks, Drug Only at 8 Months
	Comments	Repeated measures analysis of difference in symptom bother over time by treatment group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments	P-value for test of time by treatment group interaction.
	Method	Mixed Models Analysis
	Comments	Adjusted for study site
Method of Estimation	Estimation Parameter	Other
	Estimated Value	0
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Satisfaction
Description	Number of women who responded "completely satisfied" to question, "How satisfied are you with your progress?"
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

Number of women who completed satisfaction question at 10 weeks.

Arm/Group Title	Combination at 10 Weeks	Drug Only at 10 Weeks
Arm/Group Description	10 week value for women in combination arm	10 week value for women randomized to drug only
Measure Participants	134	138
Number [participants]	71 46.1%	55 35.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Combination Therapy, Drug Therapy Alone
	Comments	Null hypothesis: no difference in satisfaction at 10 weeks
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Regression, Logistic
	Comments	Controlling for clinical site and randomization stratum
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.79
	Confidence Interval	(2-Sided) 95%; 1.09 to 2.92
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ratio of odds of complete satisfaction in Combination therapy arm to Drug only arm.

7. Secondary Outcome

Title	Satisfaction
Description	Number of women who responded "completely satisfied" to question "How satisfied are you with your progress?"
Time Frame	8 months

Outcome Measure Data

Analysis Population Description

Number of participants who completed the 8 months satisfaction questions

Arm/Group Title	Combination Therapy	Drug Therapy Alone
Arm/Group Description	Women randomly assigned to this condition receive 10 weeks of anti-cholinergic medication and behavioral training.	Women assigned to this arm received 10 weeks of anti-cholinergic medication, only.
Measure Participants	115	123
Number [participants]	38 24.7%	25 16.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Combination Therapy, Drug Therapy Alone
	Comments	Null hypothesis: No difference in satisfaction at 8 months post intervention
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Regression, Logistic
	Comments	Controlling for clinical site and randomization stratum
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.03
	Confidence Interval	(2-Sided) 95%; 1.11 to 3.70
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ratio of odds of complete satisfaction in combination therapy group compared to drug only group.

8. Secondary Outcome

Title	Symptom Improvement
Description	Number of women who responded "much better" or "better" to question: "Overall, do you feel that you are much better, better, about the same, worse or much worse?"
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

Participants who completed the satisfaction item at 10 weeks.

Arm/Group Title	Combination Therapy	Drug Therapy Alone
Arm/Group Description	Women randomly assigned to this condition receive 10 weeks of anti-cholinergic medication and behavioral training.	Women assigned to this arm received 10 weeks of anti-cholinergic medication, only.
Measure Participants	134	138
Number [participants]	120 77.9%	106 69.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Combination Therapy, Drug Therapy Alone
	Comments	Null hypothesis: No difference in perceived improvement between women in combination therapy group compared to those in drug only group
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments	P-value from logistic regression analysis
	Method	Regression, Logistic
	Comments	Controlling for clinical site and randomization stratum
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.55
	Confidence Interval	(2-Sided) 95%; 1.27 to 5.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Symptom Improvement
Description	Number of women who responded "much better" or "better" to question: "Overall, do you feel that you are much better, better, about the same, worse or much worse?"
Time Frame	8 months

Outcome Measure Data

Analysis Population Description

Participants who completed the perceived improvement item at 8 months.

Arm/Group Title	Combination Therapy	Drug Therapy Alone
Arm/Group Description	Women randomly assigned to this condition receive 10 weeks of anti-cholinergic medication and behavioral training.	Women assigned to this arm received 10 weeks of anti-cholinergic medication, only.
Measure Participants	116	125
Number [participants]	80 51.9%	54 35.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Combination Therapy, Drug Therapy Alone
	Comments	Null hypothesis: No difference in perceived improvement at 8 months between women in combination therapy group compared to those in drug only group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments	Controlling for clinical site and randomization stratum
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.17
	Confidence Interval	(2-Sided) 95%; 1.83 to 5.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Participants were monitored for adverse events throughout the study period (8 months).
Arm/Group Title	Combination Therapy		Drug Therapy Alone
Arm/Group Description	Women randomly assigned to this condition receive 10 weeks of anti-cholinergic medication and behavioral training.		Women assigned to this arm received 10 weeks of anti-cholinergic medication, only.
All Cause Mortality
	Combination Therapy		Drug Therapy Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Combination Therapy		Drug Therapy Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/154 (1.3%)		2/153 (1.3%)
Cardiac disorders
Tachycardia	1/154 (0.6%)	1	0/153 (0%)	0
Gastrointestinal disorders
Small bowl obstruction	1/154 (0.6%)	2	1/153 (0.7%)	1
Renal and urinary disorders
Renal cell carcinoma	0/154 (0%)	0	1/153 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Combination Therapy		Drug Therapy Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/154 (1.3%)		1/153 (0.7%)
Cardiac disorders
Syncopal episode	1/154 (0.6%)	1	0/153 (0%)	0
Eye disorders
Glaucoma	1/154 (0.6%)	1	0/153 (0%)	0
Gastrointestinal disorders
Stomach cramping	1/154 (0.6%)	1	0/153 (0%)	0
Musculoskeletal and connective tissue disorders
Weakness	1/154 (0.6%)	1	0/153 (0%)	0
Renal and urinary disorders
Peripheral edema	0/154 (0%)	0	1/153 (0.7%)	1
Night sweats	1/154 (0.6%)	1	0/153 (0%)	0

Limitations/Caveats

Ony 68% of participants completed assigned treatment.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.