Urinary Incontinence (UI)
Conditions
Keywords
Urge urinary incontinence (UUI), Drug/Behavior treatment
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.
Interventions
BEHAVIORALBehavioral 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.
DRUGTolterodine
4mg/d for 10 weeks. Could be reduced to 2mg/d for managing side effects.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Carelon Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
21 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Symptom Distress | baseline, 10 weeks and 8 months | Urogenital distress inventory (UDI). Higher score indicates greater distress. Possible range 0 to 300. |
| 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. |
| Satisfaction | 10 weeks | Number of women who responded completely satisfied to question, How satisfied are you with your progress? |
| 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? |
| 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. |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Combination Therapy Women randomly assigned to this condition receive 10 weeks of anti-cholinergic medication and behavioral training. | 154 |
| Drug Therapy Alone Women assigned to this arm received 10 weeks of anti-cholinergic medication, only. | 153 |
| Total | 307 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Baseline to 10 Weeks | Lost to Follow-up | 15 | 12 |
| Baseline to 8 Months | Lost to Follow-up | 44 | 41 |
Baseline characteristics
| Characteristic | Drug Therapy Alone | Combination Therapy | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 47 Participants | 42 Participants | 89 Participants |
| Age, Categorical Between 18 and 65 years | 106 Participants | 112 Participants | 218 Participants |
| Age Continuous | 58.0 years STANDARD_DEVIATION 13.5 | 55.8 years STANDARD_DEVIATION 14.2 | 56.9 years STANDARD_DEVIATION 13.9 |
| Region of Enrollment United States | 153 participants | 154 participants | 307 participants |
| Sex: Female, Male Female | 153 Participants | 154 Participants | 307 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 154 | 1 / 153 |
| serious Total, serious adverse events | 2 / 154 | 2 / 153 |
Outcome results
Primary
Proportion of Women Who Meet Definition of Success
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
Population: All women who completed the 8 months assessment or were known to return to drug use prior to that time.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combination Therapy | Proportion of Women Who Meet Definition of Success | 43 participants |
| Drug Therapy Alone | Proportion of Women Who Meet Definition of Success | 41 participants |
Comparison: Kaplan Meier Lifetable analysis was used to compute the 8 month cumulative success rates.p-value: 0.7495% CI: [-0.12, 0.12]Log Rank
Secondary
Change in Incontinence Episodes
Change from baseline to 10 weeks in number of incontinence episodes per week as reported on bladder diary.
Time frame: Baseline and 10 weeks
Population: All women with valid bladder diary at baseline and 10 weeks in each treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combination Therapy | Change in Incontinence Episodes | -20.4 incontinence episodes per week | Standard Error 1.4 |
| Drug Therapy Alone | Change in Incontinence Episodes | -18.5 incontinence episodes per week | Standard Error 1.4 |
Comparison: Test of hypothesis of no difference in change in episodes between the two groups.p-value: 0.3495% CI: [-2, 5.9]ANOVA
Secondary
Change in Voids Per Day
Change from baseline to 10 weeks in frequency of voids per day as reported on bladder diary
Time frame: baseline and 10 weeks
Population: All women with valid bladder diary at baseline and 10 weeks in each treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combination Therapy | Change in Voids Per Day | -0.5 voids per day | Standard Error 0.4 |
| Drug Therapy Alone | Change in Voids Per Day | 0.3 voids per day | Standard Error 0.3 |
Comparison: Null hypothesis of no difference between arms in change in number of voids per day from baseline to 10 weeks.p-value: 0.0895% CI: [-1.7, 0.1]ANOVA
Secondary
Satisfaction
Number of women who responded completely satisfied to question How satisfied are you with your progress?
Time frame: 8 months
Population: Number of participants who completed the 8 months satisfaction questions
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combination Therapy | Satisfaction | 38 participants |
| Drug Therapy Alone | Satisfaction | 25 participants |
Comparison: Null hypothesis: No difference in satisfaction at 8 months post interventionp-value: 0.0295% CI: [1.11, 3.7]Regression, Logistic
Secondary
Satisfaction
Number of women who responded completely satisfied to question, How satisfied are you with your progress?
Time frame: 10 weeks
Population: Number of women who completed satisfaction question at 10 weeks.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combination Therapy | Satisfaction | 71 participants |
| Drug Therapy Alone | Satisfaction | 55 participants |
Comparison: Null hypothesis: no difference in satisfaction at 10 weeksp-value: 0.0295% CI: [1.09, 2.92]Regression, Logistic
Secondary
Symptom Bother
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
Population: Participants who completed OAB-q assessment at each time in each treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combination Therapy | Symptom Bother | 59.9 units on a scale | Standard Deviation 1.7 |
| Drug Therapy Alone | Symptom Bother | 23.1 units on a scale | Standard Deviation 1.8 |
| Combiniation at 8 Months | Symptom Bother | 29.0 units on a scale | Standard Deviation 1.9 |
| Drug Only at Baseline | Symptom Bother | 60.0 units on a scale | Standard Deviation 1.7 |
| Drug Only at 10 Weeks | Symptom Bother | 29.6 units on a scale | Standard Deviation 1.7 |
| Drug Only at 8 Months | Symptom Bother | 39.6 units on a scale | Standard Deviation 1.8 |
Comparison: Repeated measures analysis of difference in symptom bother over time by treatment group.p-value: 0.0005Mixed Models Analysis
Secondary
Symptom Distress
Urogenital distress inventory (UDI). Higher score indicates greater distress. Possible range 0 to 300.
Time frame: baseline, 10 weeks and 8 months
Population: All women who completed UDI at each time in each treatment group
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combination Therapy | Symptom Distress | 121.4 units on a scale | Standard Deviation 3.8 |
| Drug Therapy Alone | Symptom Distress | 47.3 units on a scale | Standard Deviation 4.1 |
| Combiniation at 8 Months | Symptom Distress | 61.9 units on a scale | Standard Deviation 4.3 |
| Drug Only at Baseline | Symptom Distress | 118.2 units on a scale | Standard Deviation 3.9 |
| Drug Only at 10 Weeks | Symptom Distress | 58.1 units on a scale | Standard Deviation 4 |
| Drug Only at 8 Months | Symptom Distress | 83.3 units on a scale | Standard Deviation 4.2 |
Comparison: Null hypothesis is that there is no difference between treatment groups in improvement in UDI over timep-value: 0.0006Mixed Models Analysis
Secondary
Symptom Improvement
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
Population: Participants who completed the satisfaction item at 10 weeks.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combination Therapy | Symptom Improvement | 120 participants |
| Drug Therapy Alone | Symptom Improvement | 106 participants |
Comparison: Null hypothesis: No difference in perceived improvement between women in combination therapy group compared to those in drug only groupp-value: 0.00895% CI: [1.27, 5.13]Regression, Logistic
Secondary
Symptom Improvement
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
Population: Participants who completed the perceived improvement item at 8 months.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combination Therapy | Symptom Improvement | 80 participants |
| Drug Therapy Alone | Symptom Improvement | 54 participants |
Comparison: Null hypothesis: No difference in perceived improvement at 8 months between women in combination therapy group compared to those in drug only group.p-value: <0.000195% CI: [1.83, 5.52]Regression, Logistic