Alfuzosin Treatment in Children and Adolescents With Hydronephrosis of Neuropathic Etiology

Phase 3

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Alfuzosin solution - 2-7 years	Alfuzosin	Alfuzosin solution, daily dose divided in 3 doses given at breakfast, lunch and dinner to children 2-7 years of age.
Alfuzosin solution - 8-16 years	Alfuzosin	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.
Alfuzosin tablet - 8-16 years	Alfuzosin	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With a Decrease From Baseline ≥ 1 in the Society of Fetal Urology (SFU) Grade of Hydronephrosis	baseline and 12 weeks (efficacy study phase)	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.

Secondary Outcome Measures