Sequencing and Combination of Mirabegron and TTNS in Overactive Bladder Syndrome: a Multicenter, Randomized, Open-label, Crossover Trial
Study Details
Study Description
Brief Summary
Research question:
A wealth of existing research has established the independent effectiveness of mirabegron and neuromodulation in the treatment of overactive bladder syndrome. Optimizing the use of these effective and well-tolerated treatment modalities is an important clinical goal and warrants further research. The primary aim of this trial is to answer the questions: how does varying the treatment sequence involving mirabegron and transcutaneous tibial nerve stimulation (TTNS) affect efficacy and patient acceptance and what is the second-line efficacy of either treatment modality?
Primary objective:
To evaluate improvement in storage symptoms, as measured by changes in Overactive Bladder Symptom Score (OABSS), International Prostate Symptom Score (IPSS) and parameters of voiding diary, in overactive bladder (OAB) patients receiving mirabegron or TTNS as first-line therapy when crossed over to second-line therapy with the opposite treatment modality
Secondary objectives:
To evaluate improvement in symptoms, as measured by changes in OABSS, IPSS and parameters of voiding diary, on first-line therapy with mirabegron or TTNS followed by combination multi-modal therapy To evaluate the effect of multi-modal treatment approach on patient's perception of treatment satisfaction and symptom control To evaluate urodynamic profiles of patients treated with multi-modal approach
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
Study design: Prospective, randomized, multicenter, open-label, cross-over trial Treatment sequence: randomized with 1:1 ratio to either Sequence A or Sequence B
Sequence A: mirabegron 50mg monotherapy x 8 weeks -> multi-modal combination treatment x 4 weeks -> TTNS monotherapy x 8 weeks Sequence B: TTNS monotherapy x 8 weeks -> multi-modal combination treatment x 4 weeks -> mirabegron 50mg monotherapy x 8 weeks
Patient population: adults ≥ 20 years who have experienced symptoms of OAB, as defined by International Continence Society (ICS) diagnostic criteria, for at least 3 months
Sample size: approximately 180 patients
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Sequence A mirabegron 50mg OD x 8 weeks, followed by mirabegron 50mg OD and TTNS for 4 weeks, followed by TTNS twice a week x 8 weeks |
Drug: mirabegron
mirabegron 50mg QD
Procedure: TTNS
transcutaneous tibial nerve stimulation
|
| Experimental: Sequence B TTNS twice a week x 8 weeks, followed by mirabegron 50mg OD and TTNS for 4 weeks, followed by mirabegron 50mg OD x 8 weeks |
Drug: mirabegron
mirabegron 50mg QD
Procedure: TTNS
transcutaneous tibial nerve stimulation
|
Outcome Measures
Primary Outcome Measures
- Changes from baseline to end of treatment (EoT) (Week 20) in OABSS [Baseline and Week 20]
Changes from baseline to Week 20 in OABSS (Overactive Bladder Symptom Score) (a lower OABSS score represents a better outcome). Symptom improvement is defined as OABSS total score decreased by ≥ 3 points at EoT
Secondary Outcome Measures
- Changes from baseline to Week 12 in OABSS [Baseline and Week 12]
Changes from baseline to Week 12 in OABSS (Overactive Bladder Symptom Score) (a lower OABSS score represents a better outcome)
- Changes from baseline to Week 12 and 20/end of treatment (EoT) in IPSS [Baseline, and Week 12 and 20]
Changes from baseline in IPSS (International Prostate Symptom Score) at Week 12 and 20 (a lower IPSS represents a better outcome)
- Change from Baseline to Week 12 and 20/end of treatment (EoT) in Mean Number of Micturitions per 24 Hours [Baseline, and Week 12 and 20]
The average number of micturitions (urinations) per 24 hours is derived from the number of times a patient urinates (excluding incontinence only episodes) per day recorded by the patient in a micturition diary for 3-days prior to clinic visits at Baseline and Week 12 and 20/end of treatment (EoT).
- Change from Baseline to Week 12 and 20/end of treatment (EoT) in Mean Number of Nocturia Episodes per 24 Hours [Baseline, and Week 12 and 20]
Nocturia is defined as waking at night one or more times to void. The average number of times a patient urinates (excluding incontinence only episodes) during sleeping time per day is derived from a micturition diary in which a patient records for 3 days prior to clinic visits at Baseline and Week 12 and 20/end of treatment (EoT).
- Change from Baseline to Week 12 and 20/end of treatment (EoT) in Mean Number of Urgency Episodes per 24 Hours [Baseline, and Week 12 and 20]
The average number of urgency episodes (the sudden, compelling desire to pass urine that is difficult to defer) is derived from episodes reocrded by the patient in a micturition diary in which a patient completes for 3 days prior to clinic visits at Baseline and Week 12 and 20/end of treatment (EoT).
- Change from Baseline to Week 12 and 20/end of treatment (EoT) in Mean Number of Urgency Incontinence Episodes per 24 Hours [Baseline, and Week 12 and 20]
The involuntary leakage of urine accompanied or immediately proceeded by urgency, derived from the number of incontinence episodes recorded by the patient in a micturition diary in which a patient completes for 3 days prior to clinic visits at Baseline and Week 12 and 20/end of treatment (EoT).
- Changes from Week 8 to Week 20 in OABSS [Week 8 to Week 20]
Changes from Week 8 to Week 20 in OABSS (Overactive Bladder Symptom Score) (a lower OABSS represents a better outcome)
- Changes from Week 8 to Week 20 in IPSS [Week 8 to Week 20]
Changes from Week 8 to Week 20 in IPSS (International Prostate Symptom Score) (a lower IPSS represents a better outcome)
- Changes from Week 8 to Week 20 in Mean Number of Micturitions per 24 Hours [Week 8 to Week 20]
The average number of micturitions (urinations) per 24 hours is derived from the number of times a patient urinates (excluding incontinence only episodes) per day recorded by the patient in a 3-day micturition diary.
- Changes from Week 8 to Week 20 in Mean Number of Nocturia Episodes per 24 Hours [Week 8 to Week 20]
Nocturia is defined as waking at night one or more times to void. The average number of times a patient urinates (excluding incontinence only episodes) during sleeping time per day is derived from the 3-day patient micturition diary.
- Changes from Week 8 to Week 20 in Mean Number of Urgency Episodes per 24 Hours [Week 8 to Week 20]
The average number of urgency episodes (the sudden, compelling desire to pass urine that is difficult to defer) derived from episodes recorded by the patient in a 3-day micturition diary
- Changes from Week 8 to Week 20 in Mean Number of Urgency Incontinence Episodes per 24 Hours [Week 8 to Week 20]
The involuntary leakage of urine accompanied or immediately proceeded by urgency, derived from the number of incontinence episodes recorded by the patient in a 3-day micturition diary
- Changes from Week 12 to Week 20 in OABSS [Week 12 to Week 20]
Changes from Week 12 to Week 20 in OABSS (Overactive Bladder Symptom Score) (a lower OABSS represents a better outcome)
- Changes from Week 12 to Week 20 in IPSS [Week 12 to Week 20]
Changes from Week 12 to Week 20 in IPSS (International Prostate Symptom Score) (a lower IPSS represents a better outcome)
- Changes from Week 12 to Week 20 in Mean Number of Micturitions per 24 Hours [Week 12 to Week 20]
The average number of micturitions (urinations) per 24 hours is derived from the number of times a patient urinates (excluding incontinence only episodes) per day recorded by the patient in a 3-day micturition diary.
- Changes from Week 12 to Week 20 in Mean Number of Nocturia Episodes per 24 Hours [Week 12 to Week 20]
Nocturia is defined as waking at night one or more times to void. The average number of times a patient urinates (excluding incontinence only episodes) during sleeping time per day is derived from the 3-day patient micturition diary.
- Changes from Week 12 to Week 20 in Mean Number of Urgency Episodes per 24 Hours [Week 12 to Week 20]
The average number of urgency episodes (the sudden, compelling desire to pass urine that is difficult to defer) derived from episodes recorded by the patient in a 3-day micturition diary
- Changes from Week 12 to Week 20 in Mean Number of Urgency Incontinence Episodes per 24 Hours [Week 12 to Week 20]
The involuntary leakage of urine accompanied or immediately proceeded by urgency, derived from the number of incontinence episodes recorded by the patient in a 3-day micturition diary
- Changes from baseline to Week 12 and 20/end of treatment (EoT) in Overactive Bladder Questionnaire-Short Form (OAB-Q-SF) score [Baseline, and Week 12 and 20]
Overactive Bladder Questionnaire-Short Form (OAB-Q-SF) is a participant-reported instrument consisting of 19 items that assess the degree to which a participant is bothered by OAB symptoms, and the degree of impact of OAB symptoms on daily life. Participants rate each item using a 6-point Likert Scale ranging from "Not at all" to "A very great deal" for the symptom bother items and "none of the time" to "All of the time" for the Health Related Quality of Life (HRQL) items.
- Changes from baseline to Week 12 and 20/end of treatment (EoT) in Bladder Assessment Tool (BAT) score [Baseline, and Week 12 and 20]
Bladder Assessment Tool (BAT) is a participant-reported instrument consisting of 17 questions regarding the symptoms, bothering, impacts and treatment satisfaction in the past 7 days. Scores range from 0 to 88, a reduction in BAT score indicates an improvement.
- Changes from baseline to Week 12 and 20/end of treatment (EoT) in Treatment Satisfaction-Visual Analog Scale (TS-VAS) score [Baseline, and Week 12 and 20]
Treatment Satisfaction-Visual Analog Scale (TS-VAS) is a quantitative instrument assessing participant improvement in participants with OAB. A score of 10 on the TS-VAS indicates complete satisfaction, whereas a positive change from baseline indicates improvement.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Adult OAB patients ≥20 years
-
Diagnosed with moderate to severe OAB (with or without urgency incontinence) based on OABSS >5 and clinical assessment, with UUI-predominant presentation, for at least 3 months
-
Able to receive TTNS and accommodate treatment logistics (30 min per on-site session, twice weekly)
-
Provided informed consent to participate in the study
Exclusion Criteria:
-
Neurologic conditions associated with OAB symptoms
-
History of stress urinary incontinence
-
Use of intravesical onabotulinumoxinA within recent 6 months
-
Postvoid residual urine volume (PVR) ≥ 100mL
-
Evidence of active urinary tract infection or urinary tract stone at screening
-
Genitourinary tract operation during the 3-month period prior to baseline
-
Confirmed or suspected genitourinary tract or pelvic malignancy
-
History of uncontrolled hypertension (systolic >160 mmHg and/or diastolic >110 mmHg)
-
History of intolerance to mirabegron
-
Patients with pacemakers or implantable defibrillators
-
Patients prone to excessive bleeding
-
Patients with nerve damage that could impact percutaneous tibial nerve or pelvic floor function
-
Patients who are pregnant or planning to become pregnant during the duration of treatment
-
History of medical conditions or presence of patient factors that, in the judgement of the investigator, would preclude adherence to study protocol
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Taipei Veterans General Hospital | Taipei City | Taiwan | 11217 |
Sponsors and Collaborators
- Taipei Veterans General Hospital, Taiwan
Investigators
- Principal Investigator: Chih-Chieh Lin, MD/Phd, Taipei Veterans General Hospital, Taiwan
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2021-09-003B