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

• Sponsor: Sanofi (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00576823
• Collaborator: (none)
• Enrollment: 25
• Locations: 12
• Arms: 3
• Duration (Months): 22
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0.1

Study Details

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
• 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: Dec 1, 2007
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Oct 1, 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 Names: 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 Names: 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 Names: 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 [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 [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 [52 weeks (efficacy and extension study phases)]

Eligibility Criteria

Criteria

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

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

	Site	City	State	Country	Postal Code
1	Sanofi-Aventis Administrative Office	Sofia		Bulgaria
2	Sanofi-Aventis Administrative Office	Laval		Canada
3	Sanofi-Aventis Administrative Office	Tallin		Estonia
4	Sanofi-Aventis Administrative Office	Mumbai		India
5	Sanofi-Aventis Administrative Office	Kuala Lumpur		Malaysia
6	Sanofi-Aventis Administrative Office	Warszawa		Poland
7	Sanofi-Aventis Administrative Office	Moscow		Russian Federation
8	Sanofi-Aventis Administrative Office	Belgrade		Serbia
9	Sanofi-Aventis Aministrative Office	Singapore		Singapore
10	Sanofi-Aventis Administrative Office	Bratislava		Slovakia
11	Sanofi-Aventis Administrative Office	Taipei		Taiwan
12	Sanofi-Aventis Administrative Office	Istanbul		Turkey

Sponsors and Collaborators

• Sanofi

Investigators

• Study Director: ICD CSD, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT00576823
• Other Study ID Numbers: EFC6269; SL770499; 2004-002397-38
• First Posted: Dec 19, 2007
• Last Update Posted: Oct 29, 2014
• Last Verified: Oct 1, 2014

• Keywords provided by Sanofi: child; bladder; neuropathic; alpha blockers
• Additional relevant MeSH terms: Urinary Bladder, Neurogenic; Hydronephrosis; Alfuzosin

Study Results

Participant Flow

Recruitment Details	This study was conducted at 19 sites in 12 countries. A total of 42 patients were screened between December 2007 and September 2008.
Pre-assignment Detail	18 of the 42 screened patients were not included in the study. The reasons were the following: Inclusion/Exclusion criteria not respected (16 patients), Subject's request (1 patient), Other (2 patients). Patients could have several reasons for not being included.

Arm/Group Title	Alfuzosin Solution - 2-7 Years	Alfuzosin Solution - 8-16 Years	Alfuzosin Tablet - 8-16 Years
Arm/Group Description	Alfuzosin solution, daily dose divided in 3 doses given at breakfast, lunch and dinner to children 2-7 years of age.	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 the tablets or preferred to take the solution or had a body weight < 30 kg.	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 the tablets and had a body weight ≥ 30 kg.
Period Title: 12-week Efficacy Phase
STARTED	12	6	7
COMPLETED	11	6	7
NOT COMPLETED	1	0	0
Period Title: 12-week Efficacy Phase
STARTED	11	6	6
COMPLETED	10	6	6
NOT COMPLETED	1	0	0

Baseline Characteristics

Arm/Group Title	Alfuzosin Solution - 2-7 Years	Alfuzosin Solution - 8-16 Years	Alfuzosin Tablet - 8-16 Years	Total
Arm/Group Description	Alfuzosin solution, daily dose divided in 3 doses given at breakfast, lunch and dinner to children 2-7 years of age.	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 the tablets or preferred to take the solution or had a body weight < 30 kg.	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 the tablets and had a body weight ≥ 30 kg.	Total of all reporting groups
Overall Participants	12	6	7	25
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	4.3 (1.5)	10.0 (1.7)	11.2 (2.3)	7.9 (4.0)
Sex: Female, Male (Count of Participants)
Female	7 58.3%	4 66.7%	5 71.4%	16 64%
Male	5 41.7%	2 33.3%	2 28.6%	9 36%
Region of Enrollment (participants) [Number]
Taiwan	0 0%	1 16.7%	1 14.3%	2 8%
Slovakia	1 8.3%	0 0%	1 14.3%	2 8%
Poland	4 33.3%	2 33.3%	2 28.6%	8 32%
Malaysia	0 0%	0 0%	1 14.3%	1 4%
Singapore	1 8.3%	0 0%	0 0%	1 4%
Turkey	1 8.3%	0 0%	0 0%	1 4%
Russian Federation	3 25%	2 33.3%	2 28.6%	7 28%
India	2 16.7%	1 16.7%	0 0%	3 12%
Type of hydronephrosis (participants) [Number]
Bilateral hydronephrosis (both kidneys affected)	11 91.7%	4 66.7%	5 71.4%	20 80%
Unilateral hydronephrosis (one kidney affected)	1 8.3%	2 33.3%	2 28.6%	5 20%
Grade of hydronephrosis (grade) [Median (Full Range) ]
Left kidney	2	1.5	2	2
Right kidney	1	2	1	1
Duration of diagnosis for hydronephrosis (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	1.83 (2.30)	5.45 (4.20)	3.35 (3.05)	3.12 (3.26)
Urinary Tract Infection (UTI) history within the last 3 months (participants) [Number]
No UTI episode	9 75%	4 66.7%	6 85.7%	19 76%
One UTI episode	2 16.7%	2 33.3%	1 14.3%	5 20%
Two UTI episodes	1 8.3%	0 0%	0 0%	1 4%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis was on the intent-to-treat (ITT) population (i.e. all included patients who received at least one dose of Alfuzosin) excluding the patients who didn't have baseline SFU grade. Patients without post-baseline SFU grade before Week 12 were included as non-responders.

Arm/Group Title	Alfuzosin Solution - 2-7 Years	Alfuzosin Solution - 8-16 Years	Alfuzosin Tablet - 8-16 Years
Arm/Group Description	Alfuzosin solution, daily dose divided in 3 doses given at breakfast, lunch and dinner to children 2-7 years of age.	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 the tablets or preferred to take the solution or had a body weight < 30 kg.	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 the tablets and had a body weight ≥ 30 kg.
Measure Participants	12	6	7
Complete response	2 16.7%	5 83.3%	3 42.9%
- Bilateral hydronephrosis	1 8.3%	3 50%	1 14.3%
- Unilateral hydronephrosis	1 8.3%	2 33.3%	2 28.6%
Partial response	3 25%	0 0%	3 42.9%

2. Secondary Outcome

Title	Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes
Description	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.
Time Frame	12 weeks (efficacy study phase)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ITT population (i.e. all included patients who received at least one dose of Alfuzosin).

Arm/Group Title	Alfuzosin Solution - 2-7 Years	Alfuzosin Solution - 8-16 Years	Alfuzosin Tablet - 8-16 Years
Arm/Group Description
Measure Participants	12	6	7
No symptomatic UTI	11 91.7%	5 83.3%	7 100%
One symptomatic UTI	0 0%	1 16.7%	0 0%
Two symptomatic UTI	1 8.3%	0 0%	0 0%

3. Secondary Outcome

Title	Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes
Time Frame	52 weeks (efficacy and extension study phases)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the exposed population (i.e. all patients who received at least one dose of Alfuzosin regardless of the amount of treatment received).

Arm/Group Title	Alfuzosin Solution - 2-7 Years	Alfuzosin Solution - 8-16 Years	Alfuzosin Tablet - 8-16 Years
Arm/Group Description
Measure Participants	12	6	7
No symptomatic UTI	8 66.7%	5 83.3%	5 71.4%
One symptomatic UTI	2 16.7%	0 0%	2 28.6%
Two symptomatic UTI	2 16.7%	0 0%	0 0%
Three symptomatic UTI	0 0%	1 16.7%	0 0%

Adverse Events

Time Frame	All Adverse Events (AE) regardless of seriousness or relationship to drug, spanning from signature of the informed consent form up to the last visit were collected.
Adverse Event Reporting Description	The analysis was performed on the exposed population (i.e. all included patients exposed to Alfuzosin regardless of the amount of treatment administered) and included all AE that developed/worsened during the 'on treatment period' (i.e. from first dose up to 2 days after the last dose of Alfuzosin).
Arm/Group Title	Afluzosin Solution - 2-7 Years		Afluzosin Solution - 8-16 Years		Afluzosin Tablets - 8-16 Years
Arm/Group Description	Alfuzosin solution, daily dose divided in 3 doses given at breakfast, lunch and dinner to children 2-7 years of age.		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 the tablets or preferred to take the solution or had a body weight < 30 kg.		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 the tablets and had a body weight ≥ 30 kg.
All Cause Mortality
	Afluzosin Solution - 2-7 Years		Afluzosin Solution - 8-16 Years		Afluzosin Tablets - 8-16 Years
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Afluzosin Solution - 2-7 Years		Afluzosin Solution - 8-16 Years		Afluzosin Tablets - 8-16 Years
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/12 (16.7%)		2/6 (33.3%)		0/7 (0%)
Gastrointestinal disorders
DIARRHOEA	0/12 (0%)		1/6 (16.7%)		0/7 (0%)
Infections and infestations
PYELONEPHRITIS	1/12 (8.3%)		0/6 (0%)		0/7 (0%)
URINARY TRACT INFECTION	0/12 (0%)		1/6 (16.7%)		0/7 (0%)
Injury, poisoning and procedural complications
FEMUR FRACTURE	1/12 (8.3%)		0/6 (0%)		0/7 (0%)
URETERIC INJURY	1/12 (8.3%)		0/6 (0%)		0/7 (0%)
Nervous system disorders
CONVULSION	0/12 (0%)		1/6 (16.7%)		0/7 (0%)
SYNCOPE	1/12 (8.3%)		0/6 (0%)		0/7 (0%)
Renal and urinary disorders
CALCULUS URINARY	1/12 (8.3%)		0/6 (0%)		0/7 (0%)
RENAL IMPAIRMENT	1/12 (8.3%)		0/6 (0%)		0/7 (0%)
Respiratory, thoracic and mediastinal disorders
COUGH	0/12 (0%)		1/6 (16.7%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Afluzosin Solution - 2-7 Years		Afluzosin Solution - 8-16 Years		Afluzosin Tablets - 8-16 Years
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/12 (75%)		5/6 (83.3%)		5/7 (71.4%)
Blood and lymphatic system disorders
EOSINOPHILIA	1/12 (8.3%)		0/6 (0%)		0/7 (0%)
Cardiac disorders
TACHYCARDIA	0/12 (0%)		0/6 (0%)		1/7 (14.3%)
Gastrointestinal disorders
DIARRHOEA	1/12 (8.3%)		0/6 (0%)		0/7 (0%)
ABDOMINAL PAIN UPPER	0/12 (0%)		0/6 (0%)		1/7 (14.3%)
DRY MOUTH	0/12 (0%)		0/6 (0%)		1/7 (14.3%)
STOMATITIS	1/12 (8.3%)		0/6 (0%)		0/7 (0%)
TOOTHACHE	0/12 (0%)		0/6 (0%)		1/7 (14.3%)
General disorders
PYREXIA	2/12 (16.7%)		2/6 (33.3%)		0/7 (0%)
OEDEMA PERIPHERAL	0/12 (0%)		1/6 (16.7%)		0/7 (0%)
Infections and infestations
CYSTITIS	3/12 (25%)		0/6 (0%)		1/7 (14.3%)
NASOPHARYNGITIS	3/12 (25%)		1/6 (16.7%)		0/7 (0%)
PHARYNGITIS	1/12 (8.3%)		1/6 (16.7%)		1/7 (14.3%)
UPPER RESPIRATORY TRACT INFECTION	2/12 (16.7%)		1/6 (16.7%)		0/7 (0%)
BRONCHITIS	1/12 (8.3%)		1/6 (16.7%)		0/7 (0%)
PYELONEPHRITIS	1/12 (8.3%)		0/6 (0%)		0/7 (0%)
URINARY TRACT INFECTION	0/12 (0%)		1/6 (16.7%)		1/7 (14.3%)
CONJUNCTIVITIS INFECTIVE	0/12 (0%)		0/6 (0%)		1/7 (14.3%)
EAR INFECTION	1/12 (8.3%)		0/6 (0%)		0/7 (0%)
GASTROINTESTINAL INFECTION	1/12 (8.3%)		0/6 (0%)		0/7 (0%)
GASTROINTESTINAL VIRAL INFECTION	1/12 (8.3%)		0/6 (0%)		0/7 (0%)
INFLUENZA	0/12 (0%)		1/6 (16.7%)		0/7 (0%)
PNEUMONIA	0/12 (0%)		1/6 (16.7%)		0/7 (0%)
TONSILLITIS	0/12 (0%)		0/6 (0%)		1/7 (14.3%)
VIRAL INFECTION	1/12 (8.3%)		0/6 (0%)		0/7 (0%)
VIRAL PHARYNGITIS	0/12 (0%)		1/6 (16.7%)		0/7 (0%)
VIRAL RHINITIS	1/12 (8.3%)		0/6 (0%)		0/7 (0%)
VIRAL UPPER RESPIRATORY TRACT INFECTION	0/12 (0%)		1/6 (16.7%)		0/7 (0%)
Injury, poisoning and procedural complications
FALL	0/12 (0%)		1/6 (16.7%)		0/7 (0%)
FOREARM FRACTURE	0/12 (0%)		1/6 (16.7%)		0/7 (0%)
IATROGENIC INJURY	0/12 (0%)		0/6 (0%)		1/7 (14.3%)
LIMB INJURY	1/12 (8.3%)		0/6 (0%)		0/7 (0%)
URETHRAL INJURY	0/12 (0%)		0/6 (0%)		1/7 (14.3%)
Nervous system disorders
DIZZINESS	0/12 (0%)		0/6 (0%)		1/7 (14.3%)
Renal and urinary disorders
LEUKOCYTURIA	1/12 (8.3%)		0/6 (0%)		0/7 (0%)
Reproductive system and breast disorders
VAGINAL DISCHARGE	1/12 (8.3%)		0/6 (0%)		0/7 (0%)
Respiratory, thoracic and mediastinal disorders
COUGH	1/12 (8.3%)		0/6 (0%)		0/7 (0%)
EPISTAXIS	0/12 (0%)		0/6 (0%)		1/7 (14.3%)
RESPIRATORY DISORDER	1/12 (8.3%)		0/6 (0%)		0/7 (0%)
Skin and subcutaneous tissue disorders
RASH	1/12 (8.3%)		1/6 (16.7%)		0/7 (0%)
DERMATITIS ALLERGIC	1/12 (8.3%)		0/6 (0%)		0/7 (0%)

Limitations/Caveats

This was an exploratory, open-label, non-comparative trial. Analyses were purely descriptive.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If no publication has occurred within 12 months after trial completion, the investigators can publish the results. Prior to the publication, the sponsor can review and request changes to the manuscript, provided they do not jeopardize the accuracy and/or the scientific value of the publication. The approval is given in writing by the sponsor, not to exceed 90 days. To protect by a property right any information the sponsor can postpone the publication, for a period not to exceed 18 months.