Alfuzosin Treatment in Children and Adolescents With Hydronephrosis of Neuropathic Etiology

Study Overview
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Brief Summary
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Primary objective was to determine efficacy of Alfuzosin in the treatment of children and adolescents 2-16 years of age with newly diagnosed or progressive hydronephrosis due to elevated detrusor Leak Point Pressure [LPP] of neuropathic etiology. Secondary objectives were: To investigate the safety and tolerability of alfuzosin 0.2 mg/kg/day in children and adolescents, To investigate the number of Urinary Tract Infection (UTI) episodes, To investigate the pharmacokinetics of Alfuzosin (population kinetics).

Detailed Description
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The study consisted of 2 phases: a 12-week efficacy phase then, a 40-week safety extension phase. All eligible subjects received alfuzosin 0.2 mg/kg/day. The formulation and the frequency was assigned by Interactive Voice Response System (IVRS) according to age group and ability to swallow tablets. Patients who completed the 12-week open-label treatment period were offered to continue in the 40-week open-label safety extension study. The treatment was the same as in the 12-week efficacy phase. All patients had a one-week follow-up period after the last dose intake.

Official Title
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12-week, Multicenter, Open-label, Non-comparative Study to Investigate Pharmacodynamic and Safety of Alfuzosin 0.2 mg/kg/Day in the Treatment of Children and Adolescents 2 - 16 Years of Age With Hydronephrosis Associated With Elevated Detrusor Leak Point Pressure of Neuropathic Etiology Followed by a 40-week Open-label Extension

Conditions
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Hydronephrosis, Neurogenic Bladder

Intervention / Treatment
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* Drug: Alfuzosin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children and adolescents of either gender 2 - 16 years of age with a detrusor Leak Point Pressure (LPP) of 40 cm water or greater and with newly diagnosed or progressive hydronephrosis either Society of Fetal Urology (SFU) grade 1, 2 or 3 due to neuropathic bladder dysfunction. Exclusion Criteria: Hydronephrosis of non-neuropathic etiology. Urological surgery in the last 4 months prior to the study. Urethral dilatation in the last 3 months prior to the baseline urodynamic assessment. α-blocker therapy in the last 4 weeks prior to the baseline urodynamic assessment. Detrusor injections of botulinum toxin in the last 6 months. Urological diseases/conditions other than functional bladder obstruction of neuropathic etiology, that can lead to upper urinary tract dilatation (e.g., bladder anomalies, ureterocele). History of intolerance to α-blocker therapy. Orthostatic hypotension. History of risk factors for Torsade de pointes (e.g., family history of Long QT Syndrome). The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alfuzosin solution - 2-7 years<br>Alfuzosin solution, daily dose divided in 3 doses given at breakfast, lunch and dinner to children 2-7 years of age. | Drug: Alfuzosin<br>* Dose: 0.2 mg/kg/day Route: oral<br>* Other names: SL770499;|
| Experimental: Alfuzosin solution - 8-16 years<br>Alfuzosin solution, daily dose divided in 3 doses given at breakfast, lunch and dinner to children and adolescents 8-16 years of age who were not able to swallow tablets or preferred to take the solution or had a body weight < 30 kg. | Drug: Alfuzosin<br>* Dose: 0.2 mg/kg/day Route: oral<br>* Other names: SL770499;|
| Experimental: Alfuzosin tablet - 8-16 years<br>Alfuzosin tablet, daily dose divided in 2 doses given at breakfast and dinner to children and adolescents 8-16 years of age who were able to swallow tablets and had a body weight ≥ 30 kg. | Drug: Alfuzosin<br>* Dose: 0.2 mg/kg/day Route: oral<br>* Other names: SL770499;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Decrease From Baseline ≥ 1 in the Society of Fetal Urology (SFU) Grade of Hydronephrosis | Hydronephrosis was investigated by ultrasound and graded using SFU classification at each time point. 'Complete response' was assessed when bilateral hydronephrosis at baseline and grade decrease from baseline ≥ 1 for both kidneys, or, unilateral hydronephrosis at baseline and grade decrease from baseline ≥ 1 for the affected kidney without worsening of the other kidney. 'Partial response' was assessed when bilateral hydronephrosis at baseline and grade decrease from baseline ≥ 1 for one kidney without worsening of the other kidney. | baseline and 12 weeks (efficacy study phase) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes | When a patient presented with symptoms such as pain, fever or hematuria (discretion of the Investigator), an urinalysis was performed including a dipstick and a quantitative urine culture. A symptomatic UTI was defined as the presence of symptoms and a positive culture with > 100 000 Colony Forming Units (CFUs) with a single organism. | 12 weeks (efficacy study phase) | 
| Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes |  | 52 weeks (efficacy and extension study phases) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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child, bladder, neuropathic, alpha blockers