alfuzosin treatment in children and adolescents with neurogenic urinary bladder dysfunction

Conditions: Neurogenic Urinary Bladder

Summary: the primary objective of the study was to evaluate the efficacy of alfuzosin in comparison to placebo on the detrusor leak point pressure (lpp) in children and adolescents 2-16 years of age with elevated detrusor lpp of neuropathic etiology and detrusor lpp ≥ 40 cm h2o. secondary objectives were: * to investigate the safety and tolerability of two doses of alfuzosin in comparison to placebo in children and adolescents, * to evaluate the effects of the two doses of alfuzosin in comparison to placebo on: * detrusor compliance, * urinary tract infection, * to investigate the pharmacokinetics of alfuzosin (population kinetics), * to evaluate the 12-month long-term safety of alfuzosin 0.1 mg/kg/day and 0.2 mg/kg/day. the study consisted of 2 periods: * a 12-week double blind treatment period where patients were to receive either alfuzosin 0.1 mg/kg/day or alfuzosin 0.2 mg/kg/day or placebo then, * a 40-week open label extension treatment period where patients were to receive either alfuzosin 0.1 mg/kg/day or alfuzosin 0.2 mg/kg/day.

patients who met the study entry criteria were randomized (2:1:2:1) to one of the 4 dosage groups (alfuzosin 0.1 mg/kg/day, matching placebo 0.1 mg/kg/day, alfuzosin 0.2 mg/mg/kg, matching placebo 0.2 mg/kg/day). patients received their treatment using either solution or tablet formulation depending on age as follows: * solution to children 2-7 years of age or, children and adolescents 8-16 years of age if they were unable to swallow tablets or they preferred to take the solution or if they had a body weight \< 30kg. the daily dose was devided in 3 doses given at at breakfast, lunch and dinner. * tablet to children and adolescents 8-16 years of age who were able to swallow tablets and had a body weight ≥ 30kg. the daily dose was devided in 2 doses given at at breakfast and dinner. patients who have completed the 12-week double-blind phase were offered to continue in the 40-week open-label extension study. * patients receiving alfuzosin continued with their dosing regimen. * patients receiving placebo were switched to alfuzosin with a dose corresponding to their randomization dose group. all patients had a one-week follow-up period after last dose intake.

Eligibility criteria:
inclusion criteria: * patient with elevated detrusor leak point pressure (lpp) of neuropathic etiology and detrusor lpp ≥ 40 cm h2o and \< 100 cm h2o. exclusion criteria: * urological surgery in the last 4 months prior to the study, * patients who have 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.

Keywords: child bladder neuropathic alpha blockers