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| ID | Type | Description | Link |
|---|---|---|---|
| 2024-515844-22-00 | EU Trial (CTIS) Number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Oxybutynin during 9 months. | Experimental | 0.1mg / kg 2x / day from inclusion and for 9 months. |
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| No oxybutynin | No Intervention | No treatment affecting bladder function |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oxybutynin 1 mg/ml Syrup | Drug | The Investigational Medicinal Product of this study is Oxybutynin 1 mg/ml Syrup (see Annex 1 for the Monograph of PMS-Oxybutynin provided by ANSM under the ATU.). It will be administered at the dose of 0.1 mg/kg/twice a day to patients randomized to the study treatment group. The dose will be adapted to the child's weight to the nearest kilogram. The recommended dosage for older children with neurologic bladder is 0.3 to 0.4mg/kg/day, whilst the dosage we will be using is effectively 0.2mg/kg/day. This is because we are taking into account the absence or pharmacological studies of oxybutynin use in children <1 year of age, as well as their specific liver metabolism. Furthermore, the dose of 0.1mg/kg twice daily is the dose used in children within the same age group in the study by Casey et al, 2012 |
| Measure | Description | Time Frame |
|---|---|---|
| success of treatment defined by the association of the three events | composite endpoints where the success of treatment at 9 months after inclusion is defined by the association of the three following events:
In presence of a pressure pop-off mechanism, only voiding pressure and bladder volume will be analyzed. | 9 months after inclusion |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of adverse events in each group | through study completion, an average of 9 months | |
| Type of adverse events in each group | adverse event or serious adverse event | through study completion, an average of 9 months |
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Inclusion Criteria:
Exclusion Criteria:
Boys, aged 3 to 6 months, diagnosed with posterior urethral valves. Urethral valves (PUV) are the most common form of congenital urethral obstruction with an incidence ranging from 1/3,000 and 1/8,000 male births.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Luke L HARPER, MD | Contact | 05 56 79 56 17 | luke.harper@chu-bordeaux.fr | |
| Aurore A CAPELLI, PhD | Contact | 05 57 82 08 77 | aurore.capelli@chu-bordeaux.fr |
| Name | Affiliation | Role |
|---|---|---|
| Laurent L FOURCADE, MD | University Hospital, Limoges | Principal Investigator |
| Alice A FAURE, MD | APHM - Hôpital Timone Enfants | Principal Investigator |
| Thomas BLANC, MD |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU de Bordeaux | Recruiting | Bordeaux | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22910256 | Background | 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. |
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| ID | Term |
|---|---|
| D052801 | Male Urogenital Diseases |
| ID | Term |
|---|---|
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| C005419 | oxybutynin |
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Phase 2 non comparative randomized multicentre clinical trial with two parallel groups:
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.
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| Incidence of urinary tract infections in each group | through study completion, an average of 9 months |
| Compliance with treatment | Compliance with treatment will be evaluated through the proportion of oxybutynin treatment interruption | 9 months after inclusion |
| Sonographic changes | Sonographic changes will be expressed as a degree of hydronephrosis at 12-15 months of life (9 months after inclusion) | 9 months after inclusion |
| Area under the plasma concentration versus time curve (AUC) of oxybutynin in treated boys over treatment | Area under the plasma concentration versus time curve (AUC) of oxybutinin in treated boys over treatment. Pharmacokinetic samples (6 points from Cmin to H+3h) at 2 weeks, 3 and 9 months after inclusion will be used to study and determine the pharmacokinetic parameters. In order to avoid having to take blood sample from the child several times, it is proposed to use a small venous catheter during the time of the pharmacokinetic samples | through study completion, an average of 9 months |
| Peak Plasma Concentration (Cmax) of oxybutynin in treated boys over treatment | Peak Plasma Concentration (Cmax) of oxybutynin in treated boys over treatment. Pharmacokinetic samples (6 points from Cmin to H+3h) at 2 weeks, 3 and 9 months after inclusion will be used to study and determine the pharmacokinetic parameters. In order to avoid having to take blood sample from the child several times, it is proposed to use a small venous catheter during the time of the pharmacokinetic samples | through study completion, an average of 9 months |
| Minimum plasma concentration (Cmin) of oxybutynin in treated boys over treatment | Minimum plasma concentration (Cmin) of oxybutynin in treated boys over treatment. Pharmacokinetic samples (6 points from Cmin to H+3h) at 2 weeks, 3 and 9 months after inclusion will be used to study and determine the pharmacokinetic parameters. In order to avoid having to take blood sample from the child several times, it is proposed to use a small venous catheter during the time of the pharmacokinetic samples | through study completion, an average of 9 months |
| Half-life of oxybutynin in treated boys over treatment | Half-life of oxybutynin in treated boys over treatment. Pharmacokinetic samples (6 points from Cmin to H+3h) at 2 weeks, 3 and 9 months after inclusion will be used to study and determine the pharmacokinetic parameters. In order to avoid having to take blood sample from the child several times, it is proposed to use a small venous catheter during the time of the pharmacokinetic samples | through study completion, an average of 9 months |
| Area under the plasma concentration versus time curve (AUC) of desethyloxybutynin (metabolite) in treated boys over treatment | Area under the plasma concentration versus time curve (AUC) of desethyloxybutynin (active metabolite) in treated boys over treatment. Pharmacokinetic samples (6 points from Cmin to H+3h) at 2 weeks, 3 and 9 months after inclusion will be used to study and determine the pharmacokinetic parameters. In order to avoid having to take blood sample from the child several times, it is proposed to use a small venous catheter during the time of the pharmacokinetic samples | through study completion, an average of 9 months |
| Peak Plasma Concentration (Cmax) of desethyloxybutynin (metabolite) in treated boys over treatment | Peak Plasma Concentration (Cmax) of desethyloxybutynin (active metabolite) in treated boys over treatment. Pharmacokinetic samples (6 points from Cmin to H+3h) at 2 weeks, 3 and 9 months after inclusion will be used to study and determine the pharmacokinetic parameters. In order to avoid having to take blood sample from the child several times, it is proposed to use a small venous catheter during the time of the pharmacokinetic samples | through study completion, an average of 9 months |
| Minimum plasma concentration (Cmin) of desethyloxybutynin (metabolite) in treated boys over treatment | Minimum plasma concentration (Cmin) of desethyloxybutynin (active metabolite) in treated boys over treatment. Pharmacokinetic samples (6 points from Cmin to H+3h) at 2 weeks, 3 and 9 months after inclusion will be used to study and determine the pharmacokinetic parameters. In order to avoid having to take blood sample from the child several times, it is proposed to use a small venous catheter during the time of the pharmacokinetic samples | through study completion, an average of 9 months |
| Half-life of desethyloxybutynin (metabolite) in treated boys over treatment | Half-life of desethyloxybutynin (active metabolite) in treated boys over treatment. Pharmacokinetic samples (6 points from Cmin to H+3h) at 2 weeks, 3 and 9 months after inclusion will be used to study and determine the pharmacokinetic parameters. In order to avoid having to take blood sample from the child several times, it is proposed to use a small venous catheter during the time of the pharmacokinetic samples | through study completion, an average of 9 months |
| creatinine clearance in each group | through study completion, an average of 9 months |
| APHP - Hôpital Necker Enfants Malades |
| Principal Investigator |
| Alaa A EL GHONEIMI, MD | APHP- Hôpital Robert Debré | Principal Investigator |
| Alexis A ARNAUD, MD | Rennes University Hospital | Principal Investigator |
| Ourdia O BOUALI, MD | University Hospital, Toulouse | Principal Investigator |
| Jean-Baptiste JB MARRET, MD | University Hospital, Caen | Principal Investigator |