Alfuzosin Treatment in Children and Adolescents With Hydronephrosis of Neuropathic Etiology (Alfahydro)

• ClinicalTrials.gov Identifier: NCT00576823
• Recruitment Status: Completed
• First Posted: December 19, 2007
• Results First Posted: February 8, 2011
• Last Update Posted: October 29, 2014
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Hydronephrosis; Neurogenic Bladder	Drug: Alfuzosin	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: December 2007
• Actual Primary Completion Date: January 2009
• Actual Study Completion Date: October 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Alfuzosin solution - 2-7 years; Alfuzosin solution, daily dose divided in 3 doses given at breakfast, lunch and dinner to children 2-7 years of age.	Drug: Alfuzosin; Dose: 0.2 mg/kg/day Route: oral; Other Name: SL770499
Experimental: Alfuzosin solution - 8-16 years; 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; Dose: 0.2 mg/kg/day Route: oral; Other Name: SL770499
Experimental: Alfuzosin tablet - 8-16 years; 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; Dose: 0.2 mg/kg/day Route: oral; Other Name: SL770499

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With a Decrease From Baseline ≥ 1 in the Society of Fetal Urology (SFU) Grade of Hydronephrosis [ Time Frame: 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 :

1. Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes [ Time Frame: 12 weeks (efficacy study phase) ]

   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.

2. Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes [ Time Frame: 52 weeks (efficacy and extension study phases) ]

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 16 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Bulgaria

Sanofi-Aventis Administrative Office

Sofia, Bulgaria

Canada

Sanofi-Aventis Administrative Office

Laval, Canada

Estonia

Sanofi-Aventis Administrative Office

Tallin, Estonia

India

Sanofi-Aventis Administrative Office

Mumbai, India

Malaysia

Sanofi-Aventis Administrative Office

Kuala Lumpur, Malaysia

Poland

Sanofi-Aventis Administrative Office

Warszawa, Poland

Russian Federation

Sanofi-Aventis Administrative Office

Moscow, Russian Federation

Serbia

Sanofi-Aventis Administrative Office

Belgrade, Serbia

Singapore

Sanofi-Aventis Aministrative Office

Singapore, Singapore

Slovakia

Sanofi-Aventis Administrative Office

Bratislava, Slovakia

Taiwan

Sanofi-Aventis Administrative Office

Taipei, Taiwan

Turkey

Sanofi-Aventis Administrative Office

Istanbul, Turkey

Sponsors and Collaborators

Sanofi

Investigators

• Study Director: ICD CSD; Sanofi

More Information

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT00576823
• Other Study ID Numbers: EFC6269; SL770499; 2004-002397-38 ( EudraCT Number )
• First Posted: December 19, 2007
• Results First Posted: February 8, 2011
• Last Update Posted: October 29, 2014
• Last Verified: October 2014

Keywords provided by Sanofi:

child; bladder; neuropathic; alpha blockers

Additional relevant MeSH terms:

Urinary Bladder, Neurogenic; Hydronephrosis; Neurologic Manifestations; Nervous System Diseases; Urinary Bladder Diseases; Urologic Diseases; Kidney Diseases; Alfuzosin; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Urological Agents