Clinical trial NCT07027020: Efficacy of Intravesical Oxybutynin in Children With Neurogenic Bladder Dysfunction
Official title: Efficacy of Intravesical Oxybutynin in Children With Neurogenic Bladder Dysfunction: A Randomized, Prospective Controlled Multi-center Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Spina Bifida
Keywords: Intravesical Oxybutynin
overactive neurogenic bladder
intermittent catheterization
Oxybutynin
anticholinergic
Pediatric patients
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
Collaborators: name: Farco-Pharma GmbH
name: Ministry of Health, France
First posted: 2025-06-18
Enrollment: 60
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Malformation of the lumbosacral region (spina bifida) affects the innervation of the bladder in children. The usual evolution leads to a neurological bladder with small capacity, poor compliancy and overactivity, exposing to incontinence and obstruction to the evacuation of urine. It is responsible for renal failure requiring dialysis and transplantation. Current therapeutics aim to evacuate urine and reduce intravesical pressure. It gradually combines 1) intermittent catheterization, 2) anticholinergics, 3) botulinum toxin (Botox®) injection into the detrusor (bladder muscle) by cystoscopy and 4) surgery (vesicostomy, Bricker, enterocystoplasty). Oxybutynin relaxes the detrusor, improves continence and reduces intravesical pressure. It is usually administered per os, but there are contraindications (glaucoma, myasthenia), side effects (constipation, dry mouth). It can be difficult to swallow for children, and drug resistance may develop. It can lead to ineffective treatment requiring therapeutic escalation. The next step, intradetrusor Botox® injection, is invasive (cystoscopy), has a limited duration of action (6 months) and must be performed under general anesthesia in children.

Surgical treatments are effective but irreversible and responsible for morbidity and mortality. A randomized study was performed demonstrating the efficacy of intravesical oxybutynin compared to oral administration in adult patients. This study found a significant increase in bladder capacity and a significant decrease in side effects in the intravesical oxybutynin group. Due to the relative difficulties of intravesical oxybutynin delivery (preparation, cost) and the more invasive nature, it is not used as an alternative to oral oxybutynin.

Our hypothesis is that this treatment may have a legitimate place in the treatment of neurogenic bladder in patients with failure of anticholinergic treatment before a therapeutic escalation requiring an invasive procedure (Botox®, enterocystoplasty) especially in children for whom repeated general anesthesia for Botox® injection may interfere with brain development. In this way, we aim to extend the time to therapeutic escalation in the pediatric population.

The main objective of the trial is to compare the efficacy on maximal bladder capacity of intravesical oxybutynin instillation versus placebo in the treatment of children with overactive neurogenic bladder (spina bifida), performing intermittent catheterization, for whom oral anticholinergic treatment is ineffective or poorly tolerated.

Detailed description: Secondary objectives of the trial :

* Secondary efficacy objectives will be analyzed following a fixed sequence in a priori ordered hypotheses: to evaluate after treatment with intravesical oxybutynin (IVO) or placebo instillation: maximum bladder pressure evolution; incontinence: time to clinical treatment failure perceived by the patient. These parameters are considered by experts to be objective markers of neurological bladder improvement, in addition to the primary urodynamic objective.
* Evaluate and compare between groups the tolerance and adverse effects of treatment.
* Evaluate and compare between groups the number of responders and continent patients after treatment
* Evaluate and compare between groups the usability of Intravesical Oxybutynin.
* Evaluate and compare between groups the evolution of quality of life.
* Evaluate and compare between groups the evolution of bladder diary data.
* Evaluate and compare between groups the evolution of other urodynamic parameters.
* Evaluate and compare between groups the evolution of renal ultrasonography parameters.
* Identify factors, among the patient's characteristics, associated with a greater probability to be a responder or non-responder to intravesical oxybutynin.

Eligibility criteria: Inclusion Criteria:

* Person affiliated to or beneficiary of a social security plan
* In failure of treatment with one or more anticholinergics defined by a response considered insufficient by the investigator after at least 4 weeks of optimal dose treatment, unable to take oral oxybutynin or intolerable adverse events
* Having performed renal ultrasonography less than 2 months ago
* Having performed cystomanometry less than 6 months ago including maximal bladder capacity and maximal bladder pressure (preferably not under oral oxybutynin treatment)
* Age between 6 and 17 years old
* Informed about study organization, having given consent to participate and each legal representative have signed the informed consent
* Having undergone the medical examination adapted to research
* Presenting overactive bladder due to spina bifida confirmed by urodynamic check-up of less than 6 months. Overactive bladder is defined according to International Children's Continence Society, (ICCS): "a urodynamic observation characterized by involuntary detrusor contractions during the filling phase which may be spontaneous or provoked"
* Carrying out intermittent catheterization for at least 6 weeks and at least three times a day
* Able and volunteer to perform intravesical catheterization and instillation (patient or parents).

Exclusion Criteria:

* Person displaying known allergy to one of the components of evaluated product (notably oxybutynin).
* Person with congestive cardiac failure
* Person with cardiac arrhythmia
* Person with tachycardia
* Person with uncontrolled hypertension
* Person under one of the following treatments : Bisphosphonates; Cytochrome P450 Inhibitors (such as ketoconazole and Erythromycin); Cholinesterase inhibitors.
* Person displaying a contraindication to evaluated product, in particular: Hypersensitivity to oxybutynin; Myasthenia; Angle-closure glaucoma; Functional or organic gastrointestinal obstruction including pyloric stenosis, paralytic ileus and intestinal atony; Serious gastro-intestinal disorders (e.g., severe ulcerative colitis and toxic megacolon); Patients who have undergone ileostomy, colostomy, severe hemorrhagic colectasis or rectocolitis; Subvesical obstruction (urethral stenosis, posterior urethra valve); Ongoing treatment with anticholinergic drugs for another indication that could not be stopped; Patient with polyuria of other origin (renal, heart, potomania); Concomitant oxygenotherapy.
* Woman of childbearing age without highly effective contraception (Sexual abstinence OR combined contraception by oral, intravaginal or transdermal ovulation inhibition OR progestin-only contraception by oral, injectable or implantable ovulation inhibition OR Intrauterine device or hormonal IUD).
* Pregnant, parturient or breastfeeding woman.
* Person deprived of liberty for judicial or administrative decision.
* Person under psychiatric care as referred in articles L. 3212-1 and L. 3213-1.
* Intradetrusor injection of botulinum toxin less than 6 months before.
* Person with hyperthyroidism
* Person with coronary cardiac disease.

Primary outcomes:
measure: Evolution of maximal bladder capacity at 4 weeks of treatment (end of follow-up)
timeFrame: 4 weeks
Secondary outcomes:
measure: Evolution of maximal bladder pressure at 4 weeks of treatment (end of follow-up)
timeFrame: 4 weeks
measure: Urinary incontinence
timeFrame: 4 weeks
measure: Evaluation of the number of side effects
timeFrame: 4 weeks
measure: Proportion of responders at 4 weeks of treatment
timeFrame: 4 weeks
measure: Proportion of continent patients at 4 weeks of treatment
timeFrame: 4 weeks
measure: Product usability measured with usability questionnaire
timeFrame: 4 weeks
measure: Standardized difference in patient quality of life calculated according to the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF) score between the beginning and the end of the study.
timeFrame: 4 weeks
measure: Standardized difference in patient quality of life calculated according to the KIDSCREEN-10 score between the beginning and the end of the study.
timeFrame: 4 weeks
measure: Evolution of the number of urinary catheterizations at 4 weeks of treatment
timeFrame: 4 weeks
measure: Evolution of the volume of urinary catheterizations at 4 weeks of treatment
timeFrame: 4 weeks
measure: Evolution of the bladder compliance at 4 weeks of treatment
timeFrame: 4 weeks
measure: Evolution of the minimum filling volume causing uninhibited detrusor contraction at 4 weeks of treatment
timeFrame: 4 weeks
measure: Evolution of the Detrusor leak point pressure at 4 weeks of treatment
timeFrame: 4 weeks
measure: Evolution of the volume of bladder filling during urine loss at 4 weeks of treatment
timeFrame: 4 weeks
measure: Evolution of renal ultrasonography at 4 weeks of treatment
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Besançon
country: France
facility: Centre Hospitalier Universitaire de Besançon
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire De Bordeaux
city: Brest
country: France
facility: Centre Hospitalier Régional Et Universitaire De Brest
city: Caen
country: France
facility: Centre Hospitalier Universitaire De Caen Normandie
city: Clermont-Ferrand
country: France
facility: Centre Hospitalier Universitaire de Clermont-Ferrand
city: Colmar
country: France
facility: Centre Hospitalier De Colmar
city: Grenoble
country: France
facility: Centre Hospitalier Universitaire Grenoble Alpes
city: Lille
country: France
facility: Centre Hospitalier Universitaire de Lille
city: Limoges
country: France
facility: Centre Hospitalier Et Universitaire De Limoges
city: Marseille
country: France
facility: Centre Hospitalier Régional De Marseille
city: Nice
country: France
facility: Fondation Lenval Nice
city: Paris
country: France
facility: Hôpital Necker Enfants Malades
city: Paris
country: France
facility: Hôpital Trousseau (chirurgie viscérale pédiatrique et néonatale)
city: Paris
country: France
facility: Hôpital Trousseau (médecine physique et de réadaptation pédiatrique)
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire de Poitiers
city: Rennes
country: France
facility: Centre Hospitalier Universitaire de Rennes
city: St Etienne
country: France
facility: Centre Hospitalier Universitaire De Saint Etienne
city: Strasbourg
country: France
facility: Les Hopitaux Universitaires De Strasbourg
city: Vandoeuvre-les-Nancy
country: France
facility: Centre Hospitalier Régional Et Universitaire de Nancy
Study officials:
References: