Enhancing Conservative Treatment for Urge Incontinence (COMBO)

• ClinicalTrials.gov Identifier: NCT00223821
• Recruitment Status: Completed
• First Posted: September 22, 2005
• Results First Posted: December 19, 2013
• Last Update Posted: December 19, 2013
• Sponsor: US Department of Veterans Affairs
• Information provided by (Responsible Party): VA Office of Research and Development ( US Department of Veterans Affairs )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Urinary Incontinence
• Interventions: Drug: Oxybutynin chloride, extended-release, individually-titrated; Behavioral: Behavior Training
• Enrollment: 166

Participant Flow

Recruitment Details	Participants were community-dwelling women with urge predominant incontinence recruited between July 2003 and January 2008.
Pre-assignment Details	Of the 166 women enrolled, 58 were found to be ineligible on clinical evaluation, 44 withdrew, and 64 were randomized.

Arm/Group Title	Drug Therapy Alone	Drug Therapy + Behavioral Training
Arm/Group Description	drug therapy alone Oxybutynin chloride, extended-release: Individually-titrated, extended-release oxybutynin chloride with management of side-effects.	drug therapy + behavioral training Oxybutynin chloride, extended-release: Individually-titrated, extended-release oxybutynin chloride with management of side-effects. Behavior Training: Behavioral training consists of teaching urge suppression strategies and pelvic floor muscle training.
Period Title: Overall Study
Started	32	32
Completed Therapy	31	28
Completed Post-treatment Assessment	31	27
Completed 6-month Follow-up	28	25
Completed	28	22
Not Completed	4	10

Baseline Characteristics

Arm/Group Title		Arm 1	Arm 2	Total
Arm/Group Description		drug therapy alone Extended release Oxybutynin Chloride : Individually-titrated, extended release oxybutynin chloride with management of side-effects.	drug therapy + behavioral training Extended release Oxybutynin Chloride : Individually-titrated, extended release oxybutynin chloride with management of side-effects. Behavior Training : Behavioral training consists of teaching urge suppression strategies and pelvic floor muscle training.	Total of all reporting groups
Overall Number of Baseline Participants		32	32	64
Baseline Analysis Population Description		[Not Specified]
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	32 participants	32 participants	64 participants
		59.3 (11.2)	57.4 (12.6)	58.4 (11.9)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	32 participants	32 participants	64 participants
	Female	32 100.0%	32 100.0%	64 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	32 participants	32 participants	64 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	32 100.0%	32 100.0%	64 100.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	32 participants	32 participants	64 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	6 18.8%	14 43.8%	20 31.3%
	White	26 81.3%	18 56.3%	44 68.8%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	32 participants	32 participants	64 participants
		32	32	64
Incontinence type; Measure Type: Number; Unit of measure: Participants	Number Analyzed	32 participants	32 participants	64 participants
Urge only		25	26	51
Mixed urge + stress		7	5	12
missing		0	1	1
Incontinence severity; Measure Type: Number; Unit of measure: Participant	Number Analyzed	32 participants	32 participants	64 participants
Mild (less than 5 episodes/wk)		4	4	8
Moderate (5-10 episodes/wk)		7	10	17
Severe (> 10 episodes/wk)		21	18	39

Outcome Measures

1. Primary Outcome

Title	Change in Incontinent Episodes Immediately Post-treatment
Description	Percent change from baseline in weekly frequency of incontinent episodes immediately post-treatment, derived from baseline and week 8 seven-day bladder diaries.
Time Frame	Baseline and immediately post-treatment - week 8

Outcome Measure Data

Analysis Population Description

Intention to treat

Arm/Group Title	Drug Therapy Alone	Drug Therapy + Behavioral Training
Arm/Group Description:	Extended release Oxybutynin Chloride : Individually-titrated, extended release oxybutynin chloride with management of side-effects.	Extended release Oxybutynin Chloride : Individually-titrated, extended release oxybutynin chloride with management of side-effects. Behavior Training : Behavioral training consists of teaching urge suppression strategies and pelvic floor muscle training.
Overall Number of Participants Analyzed	32	32
Mean (Standard Deviation); Unit of Measure: percentage change
	-88.5 (24.0)	-78.3 (32.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Drug Therapy Alone, Drug Therapy + Behavioral Training
	Comments	The effectiveness of each intervention was calculated by comparing the weekly frequency of incontinent episodes (derived from seven-day bladder diaries) during baseline to that in the immediate post-intervention period (week 8). The primary analysis was based on intent-to-treat, in which post-treatment frequency of incontinence for non-completers was derived from the most recent week of diaries.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	.16
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	ANCOVA, with baseline frequency of incontinent episodes as the covariate, was used to compare the treatment groups.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	10.2
	Confidence Interval	(2-Sided) 95%; -5.13 to 25.54
	Parameter Dispersion	Type: Standard Error of the mean; Value: 7.65
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Change in Incontinent Episodes at 12-month Follow-up
Description	Percent change from baseline in weekly frequency of incontinent episodes at 12-months post-treatment, derived from baseline and 12-month seven-day bladder diaries
Time Frame	Baseline and 12 months post-treatment

Outcome Measure Data

Analysis Population Description

Intention to treat

Arm/Group Title	Drug Therapy Alone	Drug Therapy + Behavioral Training
Arm/Group Description:	Extended release Oxybutynin Chloride : Individually-titrated, extended release oxybutynin chloride with management of side-effects.	Extended release Oxybutynin Chloride : Individually-titrated, extended release oxybutynin chloride with management of side-effects. Behavior Training : Behavioral training consists of teaching urge suppression strategies and pelvic floor muscle training.
Overall Number of Participants Analyzed	32	32
Mean (Standard Deviation); Unit of Measure: percent change
	-82.0 (26.1)	-75.2 (33.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Drug Therapy Alone, Drug Therapy + Behavioral Training
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	.37
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	ANCOVA, with baseline frequency of incontinent episodes as the covariate, was used to compare the treatment groups.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	6.8
	Confidence Interval	(2-Sided) 95%; -10.73 to 24.33
	Parameter Dispersion	Type: Standard Error of the mean; Value: 8.71
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	12 months
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	drug therapy alone Extended release Oxybutynin Chloride : Individually-titrated, extended release oxybutynin chloride with management of side-effects.	drug therapy + behavioral training Extended release Oxybutynin Chloride : Individually-titrated, extended release oxybutynin chloride with management of side-effects. Behavior Training : Behavioral training consists of teaching urge suppression strategies and pelvic floor muscle training.
All-Cause Mortality
	Arm 1	Arm 2
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Arm 1	Arm 2
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/32 (0.00%)	0/32 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm 1	Arm 2
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/32 (0.00%)	0/32 (0.00%)

Limitations and Caveats

Secondary objectives could not be achieved because, based on a conditional power calculation, the trial was stopped early for futility.

More Information

Certain Agreements

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

Results Point of Contact

• Name/Title: Kathryn L. Burgio, PhD
• Organization: Birmingham VA Medical Center
• Phone: 205-558-7064
• EMail: kburgio@uabmc.edu

Publications of Results:

Burgio KL, Goode PS, Richter HE, Markland AD, Johnson TM 2nd, Redden DT. Combined behavioral and individualized drug therapy versus individualized drug therapy alone for urge urinary incontinence in women. J Urol. 2010 Aug;184(2):598-603. doi: 10.1016/j.juro.2010.03.141. Epub 2010 Jun 19.

• Responsible Party: VA Office of Research and Development ( US Department of Veterans Affairs )
• ClinicalTrials.gov Identifier: NCT00223821
• Other Study ID Numbers: B2899-R
• First Submitted: September 14, 2005
• First Posted: September 22, 2005
• Results First Submitted: October 11, 2013
• Results First Posted: December 19, 2013
• Last Update Posted: December 19, 2013