Urinary Bladder, NeurogenicPhase 4SEPTOXNCT04819360
Botulinum Toxin A vs Anticholinergic Treatment of Neurogenic Overactive Bladder in Patients With Multiple Sclerosis
A Phase 4 study testing VESIcare 10Mg Tablet and Botox 100 UNT Injection in people with Urinary Bladder, Neurogenic and Multiple Sclerosis, run by Brigitte Schürch at 1 site in Switzerland.
Trial summary
Botulinum toxin type A injections into the detrusor at a dose of 200 units (U) of BOTOX® are a recognized second-line treatment for the treatment of adult neurogenic lower urinary tract disorders. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Urinary Bladder, Neurogenic, Multiple Sclerosis
- What is being tested?
- VESIcare 10Mg Tablet and Botox 100 UNT Injection
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Jun 2021to 21 Apr 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with multiple sclerosis (MS) with neurogenic detrusor overactivity proven by urodynamics
- Stable MS with an Expanded Disability Severity Score (EDSS) less than or equal to 6.5
- Voluntary micturitions
- Number of micturitions > 8 per day, with or without episodes of urgency and urgency incontinence
- Signed informed consent form
Who cannot join
- Pregnancy, breastfeeding
- Patients requiring self-catheterizations
- Patients unable or unwilling to learn self-catheterisation
- Recent (<12 weeks) or current treatment with botulinum toxin for any non-urological indication
- Recent (≤ 8 weeks) or current treatment with anticholinergic drugs
- Patients with a positive history or evidence of pelvic / urological abnormality (interstitial cystitis, bladder lithiasis in the 6 months preceding the screening, or any other condition / operation affecting the bladder or prostate)
Show all 21Show fewer
- Any contraindication to Vesicare®:
- Hypersensitivity to the active ingredient or to one of the excipients
- Urinary retention
- Untreated narrow-angle glaucoma
- Severe gastrointestinal illness (e.g. toxic megacolon)
- Myasthenia gravis
- Severe hepatic failure
- Hemodialysis
- Severe renal failure, or liver function disturbances of moderate severity with concomitant treatment with a strong inhibitor of the CYP3A4 isoenzyme, including patients at risk for these diseases.
- Any contraindication to BOTOX®:
- Known hypersensitivity to the active substance or to one of the excipients
- Presence of a symptomatic infection at the planned injection site(s)
- Urinary tract infection at the time of planned treatment
- Patients who present with acute urinary retention at the time of treatment and who do not regularly use bladder catheterization
- Patients who do not want and / or cannot, if necessary, perform self-intermittent catheterisation
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Injections of Botulinum Toxin A or Anticholinergic Treatment as First Line Therapy to Treat Neurogenic Overactive Bladder in Patients With Multiple Sclerosis
Botulinum toxin type A injections into the detrusor at a dose of 200 units (U) of BOTOX® are a recognized second-line treatment for the treatment of adult neurogenic lower urinary tract disorders. Anticholinergics are established as the usual first-line treatment for neurogenic detrusor hyperactivity, but are oft not sufficiently effective and have significant side effects. In patients with multiple sclerosis (MS) suffering from overactive bladder, the 200 U dose of BOTOX® is very effective but induces a risk of urinary retention in 30% of patients requiring the temporary use of self-catheterization1. At 100 U, a recent study shows the efficacy and very good tolerance of botulinum toxin A in terms of probing risk in MS patients with overactive bladder and failure of anticholinergics. Furthermore, the efficacy of anticholinergics in MS has been little studied and is also disputed.
The investigators plan to test the therapeutic alternative as the first line of treatment in two groups of randomized MS patients from a homogeneous population suffering from overactive bladder:
Read more
- a group testing the effectiveness of low doses of botulinum toxin type A (100 U, BOTOX®),
- the other group receiving the standard anticholinergic treatment (solifenacin succinate, Vesicare®).
During this pilot study, the efficacy and side effects profile of each treatment will be analyzed in order to determine the amplitudes of effect and the safety profiles in this population and in order to establish the statistical hypotheses for a subsequent randomized multicenter study. The aim of this study will be to establish the benefit of botulinum toxin at a dose of 100 U as a first-line treatment instead of anticholinergics
Read the detailed description
Botulinum toxin type A (BOTOX®) injections will performed on an outpatient basis by cystoscopy under local anesthesia. Twenty minutes after an intravesical instillation of 20 ml of 0.2% ropivacaine, the botulinum toxin is injected into the detrusor muscle using a flexible injection needle at a rate of 10 U of BOTOX® per mL (10 points of 1 mL injections). Intravenous prophylaxis (cefuroxime 1.5 g) will be performed 30 minutes before the injections.
Patients in the Vesicare® arm will be given the tablets at the baseline visit to be taken once a day in the morning for 12 weeks. For this arm, there will be no antibiotic prophylaxis.
Randomization will be carried out via eCRF in the secuTrial® environment with an integrated Interactive Web Response System (IWRS) function allowing the allocation of a participant to one of the two intervention groups. Randomization will be carried out using a randomization table in blocks of 2, predefined without the knowledge of the investigator, respecting a balanced allocation between the two groups, necessary given the modest number of participants in the study.
The intensity of therapeutic responses for each treatment is not precisely known in this patient population. As a result, there are no reliable preliminary data which would allow the investigators to calculate under these "effect size" assumptions the necessary numbers of participants to be randomized between the two intervention groups in order to demonstrate a possible superiority of treatment by injection of BOTOX® 100 U in comparison to the reference anticholinergic treatment. The comparative study will therefore only be accessible after determining the intensity of these effects.
Within the framework of a pilot study not directly comparative of the therapeutic approaches but seeking to identify the amplitude of the effects obtained independently by the two treatments, it does not appear necessary to resort to a study design with "double-dummy" to leave the patient blind to the method used. Such an approach would require the use of a sham injection by cystoscopic route in the group treated with anticholinergics and would not appear ethical in this context.
- Conditions
- Urinary Bladder, Neurogenic, Multiple Sclerosis
- Being tested
- VESIcare 10Mg Tablet, Botox 100 UNT Injection
- Keywords
- Botulinum toxin, Neurogenic bladder, Multiple sclerosis, Anticholinergic drugs
- Medical subject headings
- Urinary Bladder, Neurogenic, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VESIcare 10Mg TabletDrug
Also called Vesicare
Vesicare® 10 mg per day for 12 weeks
Vesicare 10mg 12 weeks
Botox 100 UNT InjectionDrug
Also called Botox
1 injection of Botox® 100 UNT
| Study group | Role | What they receive |
|---|---|---|
| Vesicare | Active comparator | Group 1: will be treated with an anticholinergic (Vesicare® 10 mg per day for 12 weeks) Receives: Drug: VESIcare 10Mg Tablet |
| Botox | Active comparator | Group 2: will receive an intra-detrusor injection of a low dose of botulinum toxin type A (100 U of BOTOX®). Receives: Drug: Botox 100 UNT Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Magnitude of effect - Number of micturitions per 24h
The difference in mean values of [the number of micturitions / 24 h for the last 3 days] at T0 (inclusion) and T6W (6 weeks after start of the treatment).
Measured: 6 weeks
Secondary outcomes (9)
Other parameters of effects - Number of urgent urinations per 24h
The difference in mean values of [the number of episodes of urgent urination / 24 h for the last 3 days] at T0 (inclusion) and T2W (2 weeks after start of the treatment).
The difference in mean values of [the number of episodes of urgent urination / 24 h for the last 3 days] at T0 (inclusion) and T6W (6 weeks after start of the treatment).
The difference in mean values of [the number of episodes of urgent urination / 24 h for the last 3 days] at T0 (inclusion) and T12W (12 weeks after start of the treatment).
Measured: 2, 6 and 12 weeks after treatment start
Other parameters of effects - Number of urgency urinary incontinence episodes per 24h
The difference in mean values of [the number of urgency urinary incontinence episodes / 24 h for the last 3 days] at T0 (inclusion) and T2W (2 weeks after start of the treatment).
The difference in mean values of [the number of urgency urinary incontinence episodes / 24 h for the last 3 days] at T0 (inclusion) and T6W (6 weeks after start of the treatment).
The difference in mean values of [the number of urgency urinary incontinence episodes / 24 h for the last 3 days] at T0 (inclusion) and T12W (12 weeks after start of the treatment).
Measured: 2, 6 and 12 weeks after treatment start
Other parameters of effects - Number of nocturnal micturition episodes per 24h
The difference in mean values of [the number of nocturnal micturition episodes / 24 h for the last 3 days] at T0 (inclusion) and T2W (2 weeks after start of the treatment).
The difference in mean values of [the number of nocturnal micturition episodes / 24 h for the last 3 days] at T0 (inclusion) and T6W (6 weeks after start of the treatment).
The difference in mean values of [the number of nocturnal micturition episodes / 24 h for the last 3 days] at T0 (inclusion) and T12W (12 weeks after start of the treatment).
Measured: 2, 6 and 12 weeks after treatment start
Other parameters of effects - Number of 100% dry patients
The difference in mean values of [the number of 100% dry patients / 24 h for the last 3 days] at T0 (inclusion) and T6W (6 weeks after start of the treatment).
The difference in mean values of [the number of 100% dry patients / 24 h for the last 3 days] at T0 (inclusion) and T12W (12 weeks after start of the treatment).
Measured: 6 and 12 weeks after treatment start
Other parameters of effects - Urodynamic parameter : cystomanometric capacity
The difference in cystomanometric capacity at 6 weeks after the start of the treatment, as compared to inclusion values.
Measured: 6 weeks after treatment start
Other parameters of effects - Urodynamic parameter : reflex volume at first contraction
The difference in reflex volume at first contraction at 6 weeks after the start of the treatment, as compared to inclusion values.
Measured: 6 weeks after treatment start
Other parameters of effects - Urodynamic parameter : bladder compliance
Bladder compliance describes the relationship between change in bladder volume (ΔV) and change in detrusor pressure (Δpdet).
Compliance is calculated by dividing the volume change (∆V) by the change in detrusor pressure (∆pdet) during that change in bladder volume (C= ΔV/∆pdet). It is expressed in ml/cm H2O.
Measured: 6 weeks after treatment start
Other parameters of effects - Urodynamic parameter : maximum detrusor pressure
The difference in maximum detrusor pressure at 6 weeks after the start of the treatment, as compared to inclusion values.
Measured: 6 weeks after treatment start
Other parameters of effects - Urodynamic parameter : post-void residual after flowmetry
The difference in post-void residual after flowmetry at 6 weeks after the start of the treatment, as compared to inclusion values.
Measured: 6 weeks after treatment start
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2021
- Study start1 Jun 2021
- Primary completion9 Mar 2022
- Study completion21 Apr 2024
Why it stopped: Lack of recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Urinary Bladder, NeurogenicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigitte Schürch
- Sponsor type
- University, hospital or other
- Collaborators
- Centre Hospitalier Universitaire Vaudois
- Responsible party
- Sponsor-investigator, Brigitte Schürch, Centre Hospitalier Universitaire Vaudois
- Investigators
- Brigitte Schürch, Prof., Principal investigator, Centre Hospitalier Universitaire Vaudois
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04819360
- Sponsor's protocol ID
- SEPTOX
- Acronym
- SEPTOX
- Status last verified
- Feb 2022
- First submitted
- 13 Dec 2020
- Last updated
- 27 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chermansky C, Schurch B, Rahnama'i MS, Averbeck MA, Malde S, Mancini V, Valentini F, Sahai A. How can we better manage drug-resistant OAB/DO? ICI-RS 2018. Neurourol Urodyn. 2019 Dec;38 Suppl 5:S46-S55. doi: 10.1002/nau.24055.
PubMed 31821628
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Injections of Botulinum Toxin A or Anticholinergic Treatment as First Line Therapy to Treat Neurogenic Overactive Bladder in Patients With Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT04819360
- Acronym / sponsor ID
- SEPTOX / SEPTOX
- Conditions
- Urinary Bladder, Neurogenic, Multiple Sclerosis
- Keywords
- Botulinum toxin, Neurogenic bladder, Multiple sclerosis, Anticholinergic drugs
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of recruitment
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Brigitte SchürchUniversity, hospital or other
- Collaborators
- Centre Hospitalier Universitaire Vaudois
- Study start
- 1 Jun 2021 (actual)
- Primary completion
- 9 Mar 2022 (actual)
- Study completion
- 21 Apr 2024 (actual)
- First posted
- 26 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Botulinum toxin type A injections into the detrusor at a dose of 200 units (U) of BOTOX® are a recognized second-line treatment for the treatment of adult neurogenic lower urinary tract disorders. Anticholinergics are established as the usual first-line treatment for neurogenic detrusor hyperactivity, but are oft not sufficiently effective and have significant side effects. In patients with multiple sclerosis (MS) suffering from overactive bladder, the 200 U dose of BOTOX® is very effective but induces a risk of urinary retention in 30% of patients requiring the temporary use of self-catheterization1. At 100 U, a recent study shows the efficacy and very good tolerance of botulinum toxin A in terms of probing risk in MS patients with overactive bladder and failure of anticholinergics. Furthermore, the efficacy of anticholinergics in MS has been little studied and is also disputed.
The investigators plan to test the therapeutic alternative as the first line of treatment in two groups of randomized MS patients from a homogeneous population suffering from overactive bladder:
- a group testing the effectiveness of low doses of botulinum toxin type A (100 U, BOTOX®),
- the other group receiving the standard anticholinergic treatment (solifenacin succinate, Vesicare®).
During this pilot study, the efficacy and side effects profile of each treatment will be analyzed in order to determine the amplitudes of effect and the safety profiles in this population and in order to establish the statistical hypotheses for a subsequent randomized multicenter study. The aim of this study will be to establish the benefit of botulinum toxin at a dose of 100 U as a first-line treatment instead of anticholinergics
Detailed description
Botulinum toxin type A (BOTOX®) injections will performed on an outpatient basis by cystoscopy under local anesthesia. Twenty minutes after an intravesical instillation of 20 ml of 0.2% ropivacaine, the botulinum toxin is injected into the detrusor muscle using a flexible injection needle at a rate of 10 U of BOTOX® per mL (10 points of 1 mL injections). Intravenous prophylaxis (cefuroxime 1.5 g) will be performed 30 minutes before the injections.
Patients in the Vesicare® arm will be given the tablets at the baseline visit to be taken once a day in the morning for 12 weeks. For this arm, there will be no antibiotic prophylaxis.
Randomization will be carried out via eCRF in the secuTrial® environment with an integrated Interactive Web Response System (IWRS) function allowing the allocation of a participant to one of the two intervention groups. Randomization will be carried out using a randomization table in blocks of 2, predefined without the knowledge of the investigator, respecting a balanced allocation between the two groups, necessary given the modest number of participants in the study.
The intensity of therapeutic responses for each treatment is not precisely known in this patient population. As a result, there are no reliable preliminary data which would allow the investigators to calculate under these "effect size" assumptions the necessary numbers of participants to be randomized between the two intervention groups in order to demonstrate a possible superiority of treatment by injection of BOTOX® 100 U in comparison to the reference anticholinergic treatment. The comparative study will therefore only be accessible after determining the intensity of these effects.
Within the framework of a pilot study not directly comparative of the therapeutic approaches but seeking to identify the amplitude of the effects obtained independently by the two treatments, it does not appear necessary to resort to a study design with "double-dummy" to leave the patient blind to the method used. Such an approach would require the use of a sham injection by cystoscopic route in the group treated with anticholinergics and would not appear ethical in this context.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vesicare | Active comparator | Drug: VESIcare 10Mg TabletGroup 1: will be treated with an anticholinergic (Vesicare® 10 mg per day for 12 weeks) |
| Botox | Active comparator | Drug: Botox 100 UNT InjectionGroup 2: will receive an intra-detrusor injection of a low dose of botulinum toxin type A (100 U of BOTOX®). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with multiple sclerosis (MS) with neurogenic detrusor overactivity proven by urodynamics
- Stable MS with an Expanded Disability Severity Score (EDSS) less than or equal to 6.5
- Voluntary micturitions
- Number of micturitions > 8 per day, with or without episodes of urgency and urgency incontinence
- Signed informed consent form
Key exclusion criteria (21 listed)
- Pregnancy, breastfeeding
- Patients requiring self-catheterizations
- Patients unable or unwilling to learn self-catheterisation
- Recent (<12 weeks) or current treatment with botulinum toxin for any non-urological indication
- Recent (≤ 8 weeks) or current treatment with anticholinergic drugs
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VESIcare 10Mg TabletAlso: VesicareVesicare® 10 mg per day for 12 weeks Vesicare 10mg 12 weeks | Drug | Vesicare |
| Botox 100 UNT InjectionAlso: Botox1 injection of Botox® 100 UNT | Drug | Botox |
Primary outcome
Magnitude of effect - Number of micturitions per 24h
Time frame: 6 weeks
The difference in mean values of [the number of micturitions / 24 h for the last 3 days] at T0 (inclusion) and T6W (6 weeks after start of the treatment).
9 secondary outcomes
Other parameters of effects - Number of urgent urinations per 24h
Time frame: 2, 6 and 12 weeks after treatment start
Other parameters of effects - Number of urgency urinary incontinence episodes per 24h
Time frame: 2, 6 and 12 weeks after treatment start
Other parameters of effects - Number of nocturnal micturition episodes per 24h
Time frame: 2, 6 and 12 weeks after treatment start
Other parameters of effects - Number of 100% dry patients
Time frame: 6 and 12 weeks after treatment start
Other parameters of effects - Urodynamic parameter : cystomanometric capacity
Time frame: 6 weeks after treatment start
Other parameters of effects - Urodynamic parameter : reflex volume at first contraction
Time frame: 6 weeks after treatment start
Other parameters of effects - Urodynamic parameter : bladder compliance
Time frame: 6 weeks after treatment start
Other parameters of effects - Urodynamic parameter : maximum detrusor pressure
Time frame: 6 weeks after treatment start
Other parameters of effects - Urodynamic parameter : post-void residual after flowmetry
Time frame: 6 weeks after treatment start
Results and safety
The study was stopped early (reason given: Lack of recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2024.
- Results publication: PubMed 31821628Chermansky C, Schurch B, Rahnama'i MS, Averbeck MA, Malde S, Mancini V, Valentini F, Sahai A. How can we better manage drug-resistant OAB/DO? ICI-RS 2018. Neurourol Urodyn. 2019 Dec;38 Suppl 5:S46-S55. doi: 10.1002/nau.24055.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brigitte Schürch, Prof. principal investigator
Centre Hospitalier Universitaire Vaudois
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing VESIcare 10Mg Tablet and Botox 100 UNT Injection in people with Urinary Bladder, Neurogenic and Multiple Sclerosis, run by Brigitte Schürch at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Lack of recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Magnitude of effect - Number of micturitions per 24h (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04819360, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2024.