Clinical trial NCT04526353: Early Oxybutinin Treatment for Boys With Posterior Urethral Valves
Official title: Prospective Randomized Clinical Trial of Early Oxybutinin Treatment for Boys With Posterior Urethral Valves
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Male Urogenital Diseases
Keywords: posterior urethral valves
urodynamic
anticholinergic
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2020-08-25
Enrollment: 50
Sex: MALE
Minimum age (years): 3
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 2 non comparative randomized multicentre clinical trial with two parallel groups:

* Oxybutynin (0.1 mg/kg twice daily) during 9 months.
* No oxybutynin To determine whether the observed effects of oxybutynin are really due to the treatment we need to perform a randomized clinical trial. There is insufficient evidence in the literature about the natural evolution of the bladder in boys with PUV.

Given the paucity of literature data, our objective is not to formally test the superiority of oxybutynin versus no drug but to detect and quantify the effect of oxybutynin. This is why our clinical is randomized but non-comparative.
Primary purpose: TREATMENT

Brief summary: Boys with posterior urethral valves have bladder dysfunction of varying severity. Early treatment of these children with anticholinergics is recommended by some teams, although there have never been any clear studies on the subject. To our knowledge, no comparative study of the evolution of valve bladders with or without treatment has been carried out to date.

Anticholinergic treatment, although it may be beneficial in patients with abnormal bladder function, such as the neurologic bladders ( in Spina Bifida) for example, may have side effects and may not be of benefit for this valve population. The evolution of the valves could be spontaneously favorable.

This study would be the first randomized clinical trial of early therapeutic drug intervention in the posterior urethral valve population.

Detailed description: Posterior urethral valves (VUPs) are the leading cause of subvesical obstruction in children with an incidence between 1 / 3,000 to 1 / 8,000 births. 25-45% of patients will have chronic renal failure and 10-20% will require a transplant. The association between long-term prognosis and bladder dysfunction is well known, leading many teams to suggest early initiation of treatment with anticholinergics.

However, this treatment has never been properly evaluated. In fact, a single study carried out in boys with valves taking oxybutynin from the age of 3 months to 2 years without a control group concluded that "the early use of anticholinergics in boys with VUP presenting high voiding pressures and low bladder capacity has a beneficial effect on bladder function. It is true that in children with neurologic bladders as in Spina Bifida, early treatment with anticholinergics seems to provide a benefit, but VUPs are not strictly speaking neurologic bladders. In addition, treatment with anticholinergics can have side effects and could even be harmful to the bladder, leading to myogenic bankruptcy. The only way to properly assess oxybutynin in this population is to conduct a prospective randomized study.

The proposed study includes a group treated with oxybutynin and a group without. Boys who have had valve resection for VUP within the first three months of life and who present an abnormal urodynamic assessment 3 months after valve resection will be included. Oxybutynin will be given at a dose of 0.1 mg / kg 2x / day, as syrup, in the treatment group. The control group will not have any treatment affecting bladder function. The pharmacokinetics of oxybutynin will be studied. Several urodynamic parameters including capacity or volume, voiding pressure and compliance will be studied. The objective is to perform a composite analysis that can reflect the complex functioning of the bladder. The children included will have urodynamics at the end of the study, after 9 months of treatment. The performance of urodynamic examinations will be standardized and there will be an external centralized analysis to validate the urodynamic results.

Eligibility criteria: Inclusion Criteria:

* Boys
* Aged 3 to 6 months
* Diagnosed with posterior urethral valves, and having undergone valve resection within the first 3 months of life
* Children who have had their valve resection at least 3 months before inclusion
* Having undergone urodynamic studies between 10 weeks and 6 months of age andshowing abnormal urodynamics, notably: high voiding pressure (\>60cm H2O)/ small capacity bladder (\<70% expected bladder volume)and for those without pop-off mechanisms, poor compliance (\<10ml/cmH2O)/
* Holders of parental authority affiliated to French national health insurance
* With informed consent signed by holders of parental authority

Exclusion Criteria:

* Boys with posterior urethral valves and normal urodynamics or no urodynamic assessment
* Boys in whom urodynamic assessment is not possible for medical or anatomical reasons
* Boys requiring dialysis before the age of 3 months
* Contra-indication to oxybutynin such as hypersensitivity to oxybutynin or any of the excipients, digestive obstruction, occlusive or sub-occlusive syndrome, megacolon, digestive stasis, intestinal atony, paralytic ileus, ulcerative colitis, Hemorrhagic rectocolitis, Crohn's disease, Inflammatory bowel disease, Inflammatory organic colopathy, myasthenia, congenital glaucoma

Primary outcomes:
measure: success of treatment defined by the association of the three events
timeFrame: 9 months after inclusion
Secondary outcomes:
measure: Proportion of adverse events in each group
timeFrame: through study completion, an average of 9 months
measure: Type of adverse events in each group
timeFrame: through study completion, an average of 9 months
measure: Incidence of urinary tract infections in each group
timeFrame: through study completion, an average of 9 months
measure: Compliance with treatment
timeFrame: 9 months after inclusion
measure: Sonographic changes
timeFrame: 9 months after inclusion
measure: Area under the plasma concentration versus time curve (AUC) of oxybutynin in treated boys over treatment
timeFrame: through study completion, an average of 9 months
measure: Peak Plasma Concentration (Cmax) of oxybutynin in treated boys over treatment
timeFrame: through study completion, an average of 9 months
measure: Minimum plasma concentration (Cmin) of oxybutynin in treated boys over treatment
timeFrame: through study completion, an average of 9 months
measure: Half-life of oxybutynin in treated boys over treatment
timeFrame: through study completion, an average of 9 months
measure: Area under the plasma concentration versus time curve (AUC) of desethyloxybutynin (metabolite) in treated boys over treatment
timeFrame: through study completion, an average of 9 months
measure: Peak Plasma Concentration (Cmax) of desethyloxybutynin (metabolite) in treated boys over treatment
timeFrame: through study completion, an average of 9 months
measure: Minimum plasma concentration (Cmin) of desethyloxybutynin (metabolite) in treated boys over treatment
timeFrame: through study completion, an average of 9 months
measure: Half-life of desethyloxybutynin (metabolite) in treated boys over treatment
timeFrame: through study completion, an average of 9 months
measure: creatinine clearance in each group
timeFrame: through study completion, an average of 9 months
Other outcomes:
Locations:
Study officials:
affiliation: University Hospital, Limoges
name: Laurent L FOURCADE, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: APHM - Hôpital Timone Enfants
name: Alice A FAURE, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: APHP - Hôpital Necker Enfants Malades
name: Thomas BLANC, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: APHP- Hôpital Robert Debré
name: Alaa A EL GHONEIMI, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rennes University Hospital
name: Alexis A ARNAUD, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Toulouse
name: Ourdia O BOUALI, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Caen
name: Jean-Baptiste JB MARRET, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Casey JT, Hagerty JA, Maizels M, Chaviano AH, Yerkes E, Lindgren BW, Kaplan WE, Meyer T, Cheng EY. Early administration of oxybutynin improves bladder function and clinical outcomes in newborns with posterior urethral valves. J Urol. 2012 Oct;188(4 Suppl):1516-20. doi: 10.1016/j.juro.2012.03.068. Epub 2012 Aug 19.