Effect of Electroacupuncture Versus PFMT Plus Solifenacin for Mixed Urinary Incontinence

Study Overview
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Brief Summary
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A noninferiority randomized controlled trial aimed at comparing the effect and safety of electroacupuncture versus the pelvic floor muscle training (PFMT) plus solifenacin for mixed urinary incontinence (MUI).

Detailed Description
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Participants experiencing mixed urinary incontinence will be recruited from 10 centers. A gynecologist or urologist will make the diagnosis. Central randomization will be performed by the Clinical Evaluation Center of the China Academy of Chinese Medical Sciences in Beijing. Sample size: Sample size is based on the primary outcome. According to literature, the investigators predict that MUI patient's average 72-h incontinence episode frequency of the week 1-12 will decrease by 60% from the baseline after treatment of PFMT plus solifenacin. The number of the acupuncture group is 57%. For the assessment of noninferiority, 250 participants will be needed for each group allowing for a 15% dropout (α=0.05，β=0.2，δ=15%). Quality control: A 3-level monitoring system (monitors responsible for one center, monitors responsible for all centers and monitors responsible for the whole trial) will be established to check the performance of the trial in time. Outcome assessment, completion of case report forms and data management will be under strict supervision. Data management: The Remote Dara Capture (RDC) system will be used for data entering. Both paper and electronic case report form will be reserved. A data verification plan is made.

Official Title
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Effect of Electroacupuncture Versus PFMT Plus Solifenacin for Moderate and Severe Mixed Urinary Incontinence in Female: a Multicenter, Noninferiority, Randomized Controlled Trial

Conditions
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Urinary Incontinence

Intervention / Treatment
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* Procedure: acupuncture
* Drug: solifenacin
* Procedure: PFMT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: females meet the meet the diagnostic criteria of mixed urinary incontinence aged 35-75 years moderate and severe urinary incontinence with the urinary incontinence severity index between 3 and 9 suffering from urinary incontinence at least for 3 months with the 72-h incontinence episode frequency≥2 in the baseline assessment voluntarily join the research and sign the informed consent Exclusion Criteria: pure stress urinary incontinence, pure urgency urinary incontinence, overflow incontinence and neurogenic bladder medicine use for urinary incontinence or may affect the bladder function, or taking any non-drug therapy (such as electric stimulation, bladder training and pelvic floor muscle training) in the last month symptomatic urinary tract infection and non-functional urologic disease having ever undergone an operation for urinary incontinence or on the pelvic floor (including hysterectomy) pelvic organ prolapse degree ≥2 residual urinary volume (RUV) >30 mL maximum flow rate (Qmax) <20 mL/s; be allergic to solifenacin or having contradictions for muscarine antagonist (such as urinary retention, gastric retention, myasthenia gravis, ulcerative colitis and angle closure glaucoma) diseases affect function of lower urinary tract, such as uncontrolled diabetes, multiple sclerosis, Alzheimer's disease, Parkinson's disease, spinal injury, cauda equina injury and multiple system atrophy. serious cardiovascular, pulmonary, cerebral, liver, kidney, hematopoietic system or psychiatric disease and cognitive impairment patients with severe renal dysfunction or moderate hepatic dysfunction who are using strong Cyp3a4 Inhibitor like ketoconazole unable or limited to walking, up and down stairs and running poor compliance with electroacupuncture, pelvic floor muscle training or drug pregnancy, lactation or within the 12 months after birth having a cardiac pacemaker, a metal allergy, or a severe needle phobia. volunteer of other trials

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: acupuncture<br>BL33 and BL35 of both sides are used. Every session will last for 30 minuets and will be given every other day. There are 36 sessions for each participant in all (3 session per week, 12 weeks). | Procedure: acupuncture<br>* For BL33, the needle (75mm) will be inserted at the point upper and outside of BL33. Insert the needle with a 30-45°angle to a depth of 50-60 mm. The needle will be manipulated with an even lifting, thrusting and twisting method and the sense of soreness and distention will radiate to the perineal region or the anus. For BL35, the needle will be inserted upward and outward slightly with an even lifting, thrusting and twisting method. The sense of soreness and distention will radiate to the perineal region or the anus. The electric stimulator will be put on the two pair of points with a spare-dense wave, 10/50 Hz, 0.1-5.0 mA. The current intensity will be increased until the participant can not stand.<br>* Other names: electroacupuncture;|
| Active Comparator: Solifenacin plus PFMT<br>Both PFMT and solifenacin will be given for 36 weeks. Solifenacin will be taken 5mg once daily, before or after meal. PFMT includes intensive exercises conducted in hospital and home exercises. Intensive exercises will be done once every week for the first 12 weeks and once every four weeks for the 13th to 36th week. Home exercises will be done three times daily for 36 weeks. | Drug: solifenacin<br>* Solifenacin used in this trial is produced by Astellas Pharma Europe B.V.(Country medicine accurate character No. J20090109 )<br>* Other names: competitive cholinergic receptor antagonist;Procedure: PFMT<br>* Intensity of the PFMT exercises will conform to the guideline of National Institute for Health and Clinical Excellence (NICE).<br>* Other names: pelvic floor muscle training;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Change From Baseline in 72-hour Incontinence Episode Frequency (IEF) Over Weeks 1-12 | The average 72-h IEF is calculated based on a 72-h bladder diary. All relevant time points used in the calculation in the Time Frame (baseline, weeks 1-12) | baseline, weeks 1-12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Change From Baseline in Mean 72-hour IEF During Weeks 13-24 and Weeks 25-36 | Calculated as the same way as the primary outcome. But this outcome will be assessed at different time point. | baseline, weeks 13-24, week 25-36 | 
| Percentage of Participants With ≥50% Decrease in Average 72-h Incontinence Episode Frequency | Count the number of cases with the reduction of average 72-h incontinence episode frequency ≥50% and divide it by the number of participants at baseline. | Weeks 1-12, 13-24, 25-36 | 
| Change of Episodes From Baseline in Average 72-hour Urgencies/Urination/Nocturia Episodes | The average 72-h IEF (urinary incontinence, stress urinary incontinence and urgency urinary incontinence respectively) is calculated based on a 72-h bladder diary. For example, the average 72-h incontinence episodes from the 13th to 36th week equal to the sum of 72-h incontinence episodes of the 16th, 20th, 24th, 28th, 32nd, 36th weeks divided by 6. | Baseline, weeks 1-12, 13-24, 25-36 | 
| Change From Baseline in the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) Score | The International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF (range, 0 [best]-21 [worst] outcomes, and 2.52 as minimal clinically important differences (MCID)) scores. | baseline, weeks 12, 24 and 36 | 
| Weekly Median Number of Urine Pads Used During Weeks 1-12, 13-24, and 25-36 |  | Baseline, weeks 1-12, 13-24, 25-36 | 
| the Amount of Urine Leakage (Grams) Measured by the 1-hour Pad Test at Weeks 4 and 12 | The performance of 1-hour pad test according to the International Incontinence Society: Participants were instructed to void 2 hours before the pad test. On arrival, they received a pre-weighed pad and were asked to sit and drink 500 ml sodium-free water in 15 minutes. Next, they were instructed to walk for 30 minutes, including going up and down 24 stairs. On returning to the clinic, the participants were instructed to perform several activities, including standing and sitting 10 times, coughing vigorously 10 times, running for 1 minute, picking up a coin from the floor 5 times, and putting their hands under water for 1 minute. After the activities were completed, the pad was reweighed to measure the amount of urinary leakage using a gram sensitive weight scale (Xiangshan, EK3820). | Weeks 4 and 12 | 
| Patient's Treatment Satisfaction Degree | The self-assessing satisfaction degree on a 5-point Likert scale (range, 1 [unsatisfied strongly] to 5 [satisfied strongly]) will be finished by participants to evaluate their satisfaction for the treatment. | Weeks 12, 36 | 
| Patient Global Impression Improvement | Participants will be asked to finish one item evaluating their present condition. | Weeks 12, 36 | 
| Electroacupuncture Acceptance Assessment | The acceptance of electroacupuncture will be tested within 5 minute with a 5-point scale ('0' means very difficult to accept and '4' means accept easily). Median of scores of the three times will be calculated. | Weeks 2, 6 and 12 | 
| The Number of Participants Using Urine Pads |  | Weeks 1-12, 13-24, 25-36 | 
| Change of Episodes From Baseline in Mean 72-h Incontinence Episodes |  | Weeks 1-12, 13-24, 25-36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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electroacupuncture, urinary incontinence, PFMT, Solifenacin