Electroacupuncture and Solifenacin for Urgency-predominant Mixed Urinary Incontinence (EASE-UMUI)

• ClinicalTrials.gov Identifier: NCT03787654
• Recruitment Status: Unknown
• First Posted: December 26, 2018
• Last Update Posted: February 4, 2022
• Sponsor: Guang'anmen Hospital of China Academy of Chinese Medical Sciences
• Information provided by (Responsible Party): Liu Zhishun, Guang'anmen Hospital of China Academy of Chinese Medical Sciences

Tracking Information

• First Submitted Date: December 22, 2018
• First Posted Date: December 26, 2018
• Last Update Posted Date: February 4, 2022
• Actual Study Start Date: March 1, 2019
• Estimated Primary Completion Date: December 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 24, 2018)

Change of urgency urinary incontinence episodes in average 24 hours from baseline based on 3-day voiding diary. [ Time Frame: week 12 ]

3-day voiding diary is a reliable objective method to quantify the incontinence episode frequency and are a sensitive measurement to monitor the treatment response. In voiding diary, voiding episodes, urgency episodes, incontinence episodes, the volume drunk and the pads consumed are all recorded.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 9, 2019)

• Change of urgency urinary incontinence episodes in average 24 hours from baseline based on 3-day voiding diary. [ Time Frame: week 4, week 8, week 24, week 36 ]
  3-day voiding diary is a reliable objective method to quantify the incontinence episode frequency and are a sensitive measurement to monitor the treatment response. In voiding diary, voiding episodes, urgency episodes, incontinence episodes, the volume drunk and the pads consumed are all recorded.
• Change of urinary incontinence episodes in average 24 hours from baseline based on 3-day voiding diary. [ Time Frame: week 4, week 8, week 12, week 24, week 36 ]
  3-day voiding diary is a reliable objective method to quantify the incontinence episode frequency and are a sensitive measurement to monitor the treatment response. In voiding diary, voiding episodes, urgency episodes, incontinence episodes, the volume drunk and the pads consumed are all recorded.
• Proportion of subjects with at least 50% reduce of urgency urinary incontinence episodes in average 24 hours compared with baseline based on 3-day voiding diary. [ Time Frame: week 4, week 8, week 12, week 24, week 36 ]
  3-day voiding diary is a reliable objective method to quantify the incontinence episode frequency and are a sensitive measurement to monitor the treatment response. In voiding diary, voiding episodes, urgency episodes, incontinence episodes, the volume drunk and the pads consumed are all recorded.
• Proportion of subjects with complete resolution of urgency urinary incontinence episodes in average 24 hours based on 3-day voiding diary. [ Time Frame: week 4, week 8, week 12, week 24, week 36 ]
  3-day voiding diary is a reliable objective method to quantify the incontinence episode frequency and are a sensitive measurement to monitor the treatment response. In voiding diary, voiding episodes, urgency episodes, incontinence episodes, the volume drunk and the pads consumed are all recorded.
• Proportion of subjects with at least 50% reduce of urinary incontinence episodes in average 24 hours compared with baseline based on 3-day voiding diary. [ Time Frame: week 4, week 8, week 12, week 24, week 36 ]
  3-day voiding diary is a reliable objective method to quantify the incontinence episode frequency and are a sensitive measurement to monitor the treatment response. In voiding diary, voiding episodes, urgency episodes, incontinence episodes, the volume drunk and the pads consumed are all recorded.
• Change of voiding episodes in average 24 hours from baseline based on 3-day voiding diary. [ Time Frame: week 4, week 8, week 12, week 24, week 36 ]
  3-day voiding diary is a reliable objective method to quantify the incontinence episode frequency and are a sensitive measurement to monitor the treatment response. In voiding diary, voiding episodes, urgency episodes, incontinence episodes, the volume drunk and the pads consumed are all recorded.
• Change of voiding episodes graded as 3/4 in average 24 hours from baseline based on the Patient Perception of Intensity of Urgency Scale( PPIUS). [ Time Frame: week 4, week 8, week 12, week 24, week 36 ]
  Patient Perception of Intensity of Urgency Scale (PPIUS) is recommended by the European Medicines Agency to grade the urgency of voiding. Voiding graded at 1 and 2 levels of urgency are regarded as normal or strong desire to void rather than urgency, while 3 and 4 levels are regarded as urgency episodes.
• Change of nocturia episodes in average 24 hours from baseline based on 3-day voiding diary. [ Time Frame: week 4, week 8, week 12, week 24, week 36 ]
  3-day voiding diary is a reliable objective method to quantify the incontinence episode frequency and are a sensitive measurement to monitor the treatment response. In voiding diary, voiding episodes, urgency episodes, incontinence episodes, the volume drunk and the pads consumed are all recorded.
• Change of pad consuming in average 24 hours from baseline based on 3-day voiding diary. [ Time Frame: week 4, week 8, week 12, week 24, week 36 ]
  3-day voiding diary is a reliable objective method to quantify the incontinence episode frequency and are a sensitive measurement to monitor the treatment response. In voiding diary, voiding episodes, urgency episodes, incontinence episodes, the volume drunk and the pads consumed are all recorded.
• volume change of water intake in average 24 hours from baseline based on 3-day voiding diary. [ Time Frame: week 4, week 8, week 12, week 24, week 36 ]
  3-day voiding diary is a reliable objective method to quantify the incontinence episode frequency and are a sensitive measurement to monitor the treatment response. In voiding diary, voiding episodes, urgency episodes, incontinence episodes, the volume drunk and the pads consumed are all recorded.
• Change of International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF ) score from baseline. [ Time Frame: week 4, week 8, week 12, week 24, week 36 ]
  ICIQ-UI-SF was a questionnaire developed by the International Consultation on Incontinence to evaluate the severity of incontinence and impact to QoL in the past four weeks. It contains four items: frequency, amount of leakage, impact of UI on QoL and a separate item to indicate the cause of incontinence. The score was the sum of the first three items, providing a total score ranging from 0 to 21 with a higher score indicating worse symptoms and greater impact on QoL.
• Change of Overactive bladder questionnaire short form (OABq-SF) score from baseline. [ Time Frame: week 4, week 8, week 12, week 24, week 36 ]
  OABq-SF is a validated questionnaire to assess the bother of OAB symptoms and effect on QoL in the past four weeks. It includes coping, sleep and emotional interaction. The scores were transformed to a 0- to 100-point scale, and higher scores on the symptom-severity scale indicate worse symptoms, whereas higher scores on the QoL scale indicate better quality of life.
• Proportion of subjects with adequate improvement assessed by Patient global impression improvement (PGI-I). [ Time Frame: week 12, week 36 ]
  Patient global impression improvement (PGI-I) is a scale range from 1 to 7, with 1 indicating very much better and 7 indicating very much worse. Adequate improvement is defined as a rating of 1 or 2 by PGI-I.
• Change of residual urinary volume from baseline tested by abdominal B-ultrasound. [ Time Frame: week 12 ]
  Abdominal B-ultrasound is objective way to test the residual urinary volume.

Original Secondary Outcome Measures (submitted: December 24, 2018)

• Change of urgency urinary incontinence episodes in average 24 hours from baseline based on 3-day voiding diary. [ Time Frame: week 4, week 8, week 24, week 36 ]
  3-day voiding diary is a reliable objective method to quantify the incontinence episode frequency and are a sensitive measurement to monitor the treatment response. In voiding diary, voiding episodes, urgency episodes, incontinence episodes, the volume drunk and the pads consumed are all recorded.
• Change of urinary incontinence episodes in average 24 hours from baseline based on 3-day voiding diary. [ Time Frame: week 4, week 8, week 12, week 24, week 36 ]
  3-day voiding diary is a reliable objective method to quantify the incontinence episode frequency and are a sensitive measurement to monitor the treatment response. In voiding diary, voiding episodes, urgency episodes, incontinence episodes, the volume drunk and the pads consumed are all recorded.
• Proportion of subjects with at least 50% reduce of urgency urinary incontinence episodes in average 24 hours compared with baseline based on 3-day voiding diary. [ Time Frame: week 4, week 8, week 12, week 24, week 36 ]
  3-day voiding diary is a reliable objective method to quantify the incontinence episode frequency and are a sensitive measurement to monitor the treatment response. In voiding diary, voiding episodes, urgency episodes, incontinence episodes, the volume drunk and the pads consumed are all recorded.
• Proportion of subjects with complete resolution of urgency urinary incontinence episodes in average 24 hours based on 3-day voiding diary. [ Time Frame: week 4, week 8, week 12, week 24, week 36 ]
  3-day voiding diary is a reliable objective method to quantify the incontinence episode frequency and are a sensitive measurement to monitor the treatment response. In voiding diary, voiding episodes, urgency episodes, incontinence episodes, the volume drunk and the pads consumed are all recorded.
• Proportion of subjects with at least 50% reduce of urinary incontinence episodes in average 24 hours compared with baseline based on 3-day voiding diary. [ Time Frame: week 4, week 8, week 12, week 24, week 36 ]
  3-day voiding diary is a reliable objective method to quantify the incontinence episode frequency and are a sensitive measurement to monitor the treatment response. In voiding diary, voiding episodes, urgency episodes, incontinence episodes, the volume drunk and the pads consumed are all recorded.
• Change of voiding episodes in average 24 hours from baseline based on 3-day voiding diary. [ Time Frame: week 4, week 8, week 12, week 24, week 36 ]
  3-day voiding diary is a reliable objective method to quantify the incontinence episode frequency and are a sensitive measurement to monitor the treatment response. In voiding diary, voiding episodes, urgency episodes, incontinence episodes, the volume drunk and the pads consumed are all recorded.
• Change of voiding episodes graded as 3/4 in average 24 hours from baseline based on the Patient Perception of Intensity of Urgency Scale( PPIUS). [ Time Frame: week 4, week 8, week 12, week 24, week 36 ]
  Patient Perception of Intensity of Urgency Scale (PPIUS) is recommended by the European Medicines Agency to grade the urgency of voiding. Voiding graded at 1 and 2 levels of urgency are regarded as normal or strong desire to void rather than urgency, while 3 and 4 levels are regarded as urgency episodes.
• Change of nocturia episodes in average 24 hours from baseline based on 3-day voiding diary. [ Time Frame: week 4, week 8, week 12, week 24, week 36 ]
  3-day voiding diary is a reliable objective method to quantify the incontinence episode frequency and are a sensitive measurement to monitor the treatment response. In voiding diary, voiding episodes, urgency episodes, incontinence episodes, the volume drunk and the pads consumed are all recorded.
• Change of pad consuming in average 24 hours from baseline based on 3-day voiding diary. [ Time Frame: week 4, week 8, week 12, week 24, week 36 ]
  3-day voiding diary is a reliable objective method to quantify the incontinence episode frequency and are a sensitive measurement to monitor the treatment response. In voiding diary, voiding episodes, urgency episodes, incontinence episodes, the volume drunk and the pads consumed are all recorded.
• volume change of water intake in average 24 hours from baseline based on 3-day voiding diary. [ Time Frame: week 4, week 8, week 12, week 24, week 36 ]
  3-day voiding diary is a reliable objective method to quantify the incontinence episode frequency and are a sensitive measurement to monitor the treatment response. In voiding diary, voiding episodes, urgency episodes, incontinence episodes, the volume drunk and the pads consumed are all recorded.
• Change of International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF ) score from baseline. [ Time Frame: week 4, week 8, week 12, week 24, week 36 ]
  ICIQ-UI-SF was a questionnaire developed by the International Consultation on Incontinence to evaluate the severity of incontinence and impact to QoL in the past four weeks. It contains four items: frequency, amount of leakage, impact of UI on QoL and a separate item to indicate the cause of incontinence. The score was the sum of the first three items, providing a total score ranging from 0 to 21 with a higher score indicating worse symptoms and greater impact on QoL.
• Change of Overactive bladder questionnaire short form (OABq-SF) score from baseline. [ Time Frame: week 4, week 8, week 12, week 24, week 36 ]
  OABq-SF is a validated questionnaire to assess the bother of OAB symptoms and effect on QoL in the past four weeks. It includes coping, sleep and emotional interaction. The scores were transformed to a 0- to 100-point scale, and higher scores on the symptom-severity scale indicate worse symptoms, whereas higher scores on the QoL scale indicate better quality of life.
• Proportion of subjects with different degrees of satisfaction assessed by Patient global impression improvement (PGI-I). [ Time Frame: week 12, week 36 ]
  Patient global impression improvement (PGI-I) is a scale range from 1 to 7, with 1 indicating very much better and 7 indicating very much worse.
• Proportion of subjects with at least moderate degree of satisfaction assessed by Patient global impression improvement (PGI-I). [ Time Frame: week 12, week 36 ]
  Patient global impression improvement (PGI-I) is a scale range from 1 to 7, with 1 indicating very much better and 7 indicating very much worse.
• Change of residual urinary volume from baseline tested by abdominal B-ultrasound. [ Time Frame: week 12 ]
  Abdominal B-ultrasound is objective way to test the residual urinary volume.

Current Other Pre-specified Outcome Measures (submitted: August 30, 2020)

• Proportion of subjects bearing expectancy towards acupuncture AND proportion of subjects bearing expectancy towards drugs. [ Time Frame: baseline ]
  Expectancy of acupuncture and drugs will be recorded at baseline. Participants in the electroacupuncture and sham electroacupuncture groups will be asked to answer: "Do you think acupuncture is effective in improving the symptoms of incontinence?" Subjects will choose answer from "Have no idea", "Yes" or "No". Participants in the solifenacin group will be asked to answer: "Do you think drug is effective in improving the symptoms of incontinence?" Subjects will choose answer from "Have no idea", "Yes" or "No".
• Proportion of subjects successfully blinded [ Time Frame: week 12 ]
  Within 5 minutes after any treatment in week 12, subjects will be asked the question that: "Do you think you have received traditional electroacupuncture in the past 12 weeks?" Answer will be chosen from "Yes" or "No". The answer of "yes" indicates successful blinding.
• Incidence of adverse events [ Time Frame: week 0-36 ]
  Side effects induced by Solifenacin mainly include dry mouth, dry eye and constipation. Unintended events and feelings related to EA and SEA include broken needles, fainting, bleeding, bruising, infection and aposteme, unbearable ache (VAS≥8), vomiting, nausea, palpitations, dizziness, headache, anorexia and insomnia, etc. Adverse events irrelevant with the treatment will also be recorded in detail.

Original Other Pre-specified Outcome Measures (submitted: December 24, 2018)

• Proportion of subjects bearing expectancy towards acupuncture [ Time Frame: baseline ]
  Expectancy of acupuncture will be recorded at baseline. Participants will be asked to answer two questions: "In general, do you believe acupuncture is effective in treating diseases?" and "Do you think acupuncture is effective in improving the symptoms of incontinence?" Subjects will choose answer from "Have no idea", "Yes" or "No".
• Proportion of subjects successfully blinded [ Time Frame: week 12 ]
  Within 5 minutes after any treatment in week 12, subjects will be asked the question that: "Do you think you have received traditional electroacupuncture in the past 12 weeks?" Answer will be chosen from "Have no idea", "Yes" or "No". The answer of "have no idea" indicates successful blinding.
• Incidence of adverse events [ Time Frame: week 0-36 ]
  Side effects induced by Solifenacin mainly include dry mouth, dry eye and constipation. Unintended events and feelings related to EA and SEA include broken needles, fainting, bleeding, bruising, infection and aposteme, unbearable ache (VAS≥8), vomiting, nausea, palpitations, dizziness, headache, anorexia and insomnia, etc. Adverse events irrelevant with the treatment will also be recorded in detail.

Descriptive Information

• Brief Title: Electroacupuncture and Solifenacin for Urgency-predominant Mixed Urinary Incontinence
• Official Title: Effect of Electroacupuncture for Women With Urgency-predominant Mixed Urinary Incontinence: a Three Armed Non-inferior Randomized Controlled Trial

Brief Summary

The study is to determine the effect of electroacupuncture in female patients with urgency-predominant mixed urinary incontinence. A three-arm non-inferior randomized controlled trial (RCT) using electroacupuncture, sham electroacupuncture and solifenacin with a total sample of 282 is proposed.

The hypothesis is that the improvement (difference in number of urgency urinary incontinence episodes between baseline and 12-week evaluation) in the electroacupuncture group would be 50% or less of the difference in the improvement between the Solifenacin and the sham electroacupuncture groups.

Detailed Description

Mixed urinary incontinence (MUI) features complaint or involuntary loss of urine associated with urgency and also with effort or physical exertion or on sneezing or coughing. It is regarded as urgency-predominant mixed urinary incontinence (UMUI) when sudden sensation of voiding accompanied by uncontrolled incontinence domains the symptoms. UMUI can bring shame and inconvenience to patients.

As first-line medicine for urge-predominant urinary incontinence, Solifenacin can reduce urgency urinary incontinence episodes in 24 hours. However, the side effects tend to bring about poor compliance among patients.

Acupuncture might be effective in treating UMUI. Previous research indicated that electroacupuncture might be noninferior to pelvic floor muscle training plus Solifenacin in reducing the urgency incontinence episodes of UMUI women. However, that study didn't focuse on UMUI exclusively, thus unable to decide whether electroacupuncture is effective in the treatment of UMUI.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Masking Description:

participants in electroacupuncture and sham electroacupuncture groups are blinded, and solifenacin group is open.

Primary Purpose: Treatment

Condition

• Mixed Urinary Incontinence
• Urgency-predominant Mixed Urinary Incontinence

Intervention

• Device: electroacupuncture

  BL33 and BL35 are inserted by needles of 0.30×75mm size till a depth of 60~70mm. SP6 is inserted by needle of 0.30×40mm size till a depth of 25-30mm. After manipulation and deqi sensation generation, the electrodes will be attached to the acupoints transversely with 20Hz continuous wave and an electricity current of 2mA-6.5mA at BL33 and BL35, and 1-3.5mA at SP6. The current is adjusted from zero to the degree where patients can tolerate.

  Subjects receive 3 sessions per week（every other day ideally) for 12 weeks, 36 sessions in total.

  Other Name: EA group
• Device: sham electroacupuncture

  In sham electroacupuncture group, sham acupoints 1 cun(≈15mm） horizontally outwardly lateral to BL33 and BL35, and 0.5 cun (≈10mm) horizontally behind SP6 are stimulated by needles of 0.30×40mm size. The needles are inserted to a depth of 2-3mm to stand still, without any manipulation and sensation of deqi. The electrodes will also be attached to needles with an electricity current of 0.1-0.3mA.

  The sessions will be the same as the electroacupuncture group.

  Other Name: SEA group
• Drug: Solifenacin
  Subjects take solifenacin 5-10mg per day for a succession of 36 weeks. The dose change is decided by doctors under a comprehensive consideration of side effects and Patient Global Symptom Control (PGSC), which is applied to evaluate the effectiveness of Solifenacin at the 4th, 8th, 12th and 24th week.The medicine can be discontinued at any time if the adverse effect is rather severe.
  Other Name: Drug group

Study Arms

• Experimental: electroacupuncture group
  Acupoints of bilateral Zhongliao (BL33), Huiyang (BL35) and Sanyinjiao (SP6) are stimulated by Huatuo Brand disposable needles and SDZ-V electronic apparatus.
  Intervention: Device: electroacupuncture
• Sham Comparator: sham electroacupuncture group
  Sham acupoints 1 cun(≈15mm) horizontally outwardly lateral to BL33 and BL35, and 0.5 cun(≈10mm) horizontally behind SP6 are stimulated superficially with a small electricity current by needles of 0.30×40mm size and SDZ-V electronic apparatus.
  Intervention: Device: sham electroacupuncture
• Active Comparator: Solifenacin group
  subjects will orally take Solifenacin 5-10mg per day.
  Intervention: Drug: Solifenacin

• Publications *: Sun Y, Liu Y, Su T, Sun J, Wu Y, Liu Z. Electroacupuncture versus solifenacin for women with urgency-predominant mixed urinary incontinence: a protocol for a three-armed non-inferiority randomized controlled trial. BMC Complement Med Ther. 2020 Jan 23;20(1):18. doi: 10.1186/s12906-019-2784-1.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: December 24, 2018): 282
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 30, 2023
• Estimated Primary Completion Date: December 30, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Female patients diagnosed with mixed urinary incontinence in accordance with EAU guideline by history intaking and physical examination[8];
2. Age between 18 and 80 years old;
3. Urgency index greater than stress index by MESA questionnaire[12];
4. At least 4 episodes of urgency urinary incontinence in 72-hour voiding diary;
5. With MUI for at least 3 months, and more than 50% of the total incontinence episodes is urgency one in 72-hour voiding diary;
6. Positive cough test;
7. A voluntarily-signed written informed content.

Exclusion Criteria:

1. Having pure stress urinary incontinence, pure urgency urinary incontinence, overflow urinary incontinence or neurogenic bladder;
2. Uncontrolled urinary tract infection;
3. Tumor in urinary system or pelvic organs;
4. Pelvic organ prolapse≥degreeⅡ;
5. Residual urine volume≥100ml;
6. Maximum flow rate<15ml/s;
7. Treated incontinence by acupuncture or positive medications, such as antimuscarinic drug within the past 1 month;
8. Underwent surgery of anti-incontinence or in pelvic area, metrectomy included;
9. Complication of uncontrolled diabetes and severe hypertension;
10. Complicated diseases in nerves system that could hamper hypourethral function, such as Multiple sclerosis, senile dementia, Parkinson's disease, spinal cord injury, cauda equina nerve injury and multiple system atrophy;
11. Severe complications in cardiac, lungs, cerebrum, hepar, renal system, psychonosology and coagulation function, or obvious cognitive disability;
12. Installed a cardiac pacemaker;
13. Allergic to solifenacin or with contraindications to antimuscarinic drug, like urinary retention, gastrointestinal peristalsis paralysis, myasthenia gravis, ulcerative colitis, angle-closure glaucoma;
14. Allergic to metal or intolerant to the stimulation of electroacupuncture;
15. Already with child or plan to conceive in the future 1 year, or within 1 year after delivery.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03787654
• Other Study ID Numbers: 2018-163-KY
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Liu Zhishun, Guang'anmen Hospital of China Academy of Chinese Medical Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Guang'anmen Hospital of China Academy of Chinese Medical Sciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Zhishun Liu, PhD; Guanganmen Hospital

• PRS Account: Guang'anmen Hospital of China Academy of Chinese Medical Sciences
• Verification Date: February 2022