ALFACHIN: Alfuzosin Treatment in Children and Adolescents With Neurogenic Urinary Bladder Dysfunction

• Sponsor: Sanofi (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00549939
• Collaborator: (none)
• Enrollment: 172
• Locations: 18
• Arms: 3
• Duration (Months): 26
• Patients Per Site: 9.6
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Neurogenic Urinary Bladder	Drug: Alfuzosin; Drug: Placebo	Phase 3

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 172 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 12-week, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Investigate the Efficacy, Pharmacodynamic and Safety of 2 Doses of Alfuzosin (0.1 mg/kg/Day, 0.2 mg/kg/Day) in the Treatment of Children and Adolescents 2-16 Years With Elevated Detrusor Leak Point Pressure of Neuropathic Etiology Followed by a 40-week Open-label Extension
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Matching placebo 0.1 mg/kg/day or 0.2 mg/kg/day	Drug: Placebo; Form: matching solution or matching tablet according to age Route: oral Dose: daily dose adjusted to body weight
Experimental: Alfuzosin 0.1 mg/kg/day	Drug: Alfuzosin; Form: solution or tablet according to age Route: oral Dose: daily dose adjusted to body weight; Other Names: SL770499
Experimental: Alfuzosin 0.2 mg/kg/day	Drug: Alfuzosin; Form: solution or tablet according to age Route: oral Dose: daily dose adjusted to body weight; Other Names: SL770499

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Detrusor Leak Point Pressure (LPP) < 40 cm H2O [12 weeks (double blind treatment period)]

   Detrusor Leak Point Pressure (LPP) was measured by cystometry. For each measure, 2 or 3 cystometries were carried out depending on the difference between the 2 first LPP values (if the difference ≥ 20 cm H2O, a 3rd cystometry was done). The lowest value was retained. Investigators reading was then consolidated by the review of all cystometry data by 2 external "Expert Reviewers", who were blinded for the study treatment. The analysis was performed on consolidated investigators data (i.e. endorsed by the Investigator taking into account reviewers opinion).

Secondary Outcome Measures

1. Detrusor Leak Point Pressure (LPP) [baseline and 12 weeks (double blind treatment period)]

   Detrusor Leak Point Pressure (LPP) was assessed at baseline and 12 weeks as described for the primary outcome measure.

2. Absolute Change in Detrusor LPP [12 weeks ((double blind treatment period)]

   Absolute change = Detrusor LPP at 12 weeks - Detrusor LPP at baseline

3. Relative Change in Detrusor LPP [12 weeks (double blind treatment period)]

   Relative change = 100 * (Detrusor LPP at 12 weeks - Detrusor LPP at baseline) / Detrusor LPP at baseline

4. Detrusor Compliance [baseline and 12 weeks (double blind treatment period)]

   Detrusor compliance is defined as the relationship between change in detrusor volume and change in detrusor pressure. It was calculated by dividing the volume change (ΔV) by the change in detrusor pressure (Δpdet) during that change in detrusor volume at leak point (C= ΔV/Δpdet).

5. Relative Change in Detrusor Compliance [12 weeks (double blind treatment period)]

   Relative change = 100 * (Detrusor compliance at 12 weeks - Detrusor compliance at baseline) / Detrusor compliance at baseline

6. Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes [12 weeks (double blind treatment period)]

   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.

7. Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes [52 weeks (double blind treatment period + open label extension treatment period)]

   Symptomatic UTI episodes were assessed similar to the previous outcome measure but for a longer follow-up period.

Eligibility Criteria

Criteria

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

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sanofi-Aventis Administrative Office	Bridgewater	New Jersey	United States	08807
2	Sanofi-Aventis Administrative Office	Sofia		Bulgaria
3	Sanofi-Aventis Administrative Office	Laval		Canada
4	Sanofi-Aventis Administrative Office	Tallinn		Estonia
5	Sanofi-Aventis Administrative Office	Paris		France
6	Sanofi-Aventis Administrative Office	Berlin		Germany
7	Sanofi-Aventis Administrative Office	Mumbai		India
8	Sanofi-Aventis Administrative Office	Kuala Lumpur		Malaysia
9	Sanofi-Aventis Administrative Office	Makati City		Philippines
10	Sanofi-Aventis Administrative Office	Warszawa		Poland
11	Sanofi-Aventis Administrative Office	Porto Salvo		Portugal
12	Sanofi-Aventis Aministrative Office	Moscow		Russian Federation
13	Sanofi-Aventis Administrative Office	Belgrade		Serbia
14	Sanofi-Aventis Administrative Office	Singapore		Singapore
15	Sanofi-Aventis Administrative Office	Bratislava		Slovakia
16	Sanofi-Aventis Administrative Office	Barcelona		Spain
17	Sanofi-Aventis Administrative Office	Taipei		Taiwan
18	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: NCT00549939
• Other Study ID Numbers: EFC5722; 2004-002397-38
• First Posted: Oct 26, 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; Alfuzosin

Study Results

Participant Flow

Recruitment Details	The study was conducted at 55 sites in 18 countries. A total of 261 patients were screened between September 2007 and November 2008.
Pre-assignment Detail	172/261 patients were randomized in the 12-week double blind phase. 89/261 patients were not randomized for the following reasons: Adverse event (1 patient*), Inclusion/Exclusion criteria not met (69 patients*), Subject's request (11 patients*), Other (13 patients*). '*' Patients could have several reasons.

Arm/Group Title	Placebo	Alfuzosin 0.1 mg/kg/Day	Alfuzosin 0.2 mg/kg/Day
Arm/Group Description	Alfuzosin 0.1 mg/kg/day matching placebo or Alfuzosin 0.2 mg/kg/day matching placebo
Period Title: 12-week Double Blind Treatment Period
STARTED	57	57	58
COMPLETED	56	55	56
NOT COMPLETED	1	2	2
Period Title: 12-week Double Blind Treatment Period
STARTED	0	80	83
COMPLETED	0	75	78
NOT COMPLETED	0	5	5

Baseline Characteristics

Arm/Group Title	Placebo	Alfuzosin 0.1 mg/kg/Day	Alfuzosin 0.2 mg/kg/Day	Total
Arm/Group Description	Alfuzosin 0.1 mg/kg/day matching placebo or Alfuzosin 0.2 mg/kg/day matching placebo	Total of all reporting groups
Overall Participants	57	57	58	172
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.3 (4.4)	7.9 (3.9)	8.7 (3.9)	8.3 (4.0)
Sex: Female, Male (Count of Participants)
Female	28 49.1%	27 47.4%	30 51.7%	85 49.4%
Male	29 50.9%	30 52.6%	28 48.3%	87 50.6%
Region of Enrollment (participants) [Number]
United States	6 10.5%	7 12.3%	5 8.6%	18 10.5%
Portugal	2 3.5%	1 1.8%	3 5.2%	6 3.5%
Serbia	4 7%	6 10.5%	7 12.1%	17 9.9%
Taiwan	0 0%	1 1.8%	1 1.7%	2 1.2%
Estonia	1 1.8%	1 1.8%	1 1.7%	3 1.7%
Slovakia	6 10.5%	7 12.3%	1 1.7%	14 8.1%
Spain	2 3.5%	3 5.3%	2 3.4%	7 4.1%
Turkey	1 1.8%	2 3.5%	3 5.2%	6 3.5%
Russian Federation	8 14%	7 12.3%	4 6.9%	19 11%
India	2 3.5%	9 15.8%	9 15.5%	20 11.6%
France	1 1.8%	2 3.5%	4 6.9%	7 4.1%
Canada	3 5.3%	1 1.8%	2 3.4%	6 3.5%
Malaysia	3 5.3%	0 0%	0 0%	3 1.7%
Poland	15 26.3%	10 17.5%	14 24.1%	39 22.7%
Germany	3 5.3%	0 0%	2 3.4%	5 2.9%
Urinary Tract Infection (UTI) history in the last 3 months (participants) [Number]
No UTI episode	48 84.2%	50 87.7%	40 69%	138 80.2%
One UTI episode	8 14%	5 8.8%	16 27.6%	29 16.9%
Two UTI episodes	1 1.8%	2 3.5%	2 3.4%	5 2.9%
Study drug formulation (participants) [Number]
Solution (2-7 years)	28 49.1%	28 49.1%	28 48.3%	84 48.8%
Solution (8-16 years)	8 14%	10 17.5%	9 15.5%	27 15.7%
Tablets (8-16 years)	21 36.8%	19 33.3%	21 36.2%	61 35.5%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Detrusor Leak Point Pressure (LPP) < 40 cm H2O
Description	Detrusor Leak Point Pressure (LPP) was measured by cystometry. For each measure, 2 or 3 cystometries were carried out depending on the difference between the 2 first LPP values (if the difference ≥ 20 cm H2O, a 3rd cystometry was done). The lowest value was retained. Investigators reading was then consolidated by the review of all cystometry data by 2 external "Expert Reviewers", who were blinded for the study treatment. The analysis was performed on consolidated investigators data (i.e. endorsed by the Investigator taking into account reviewers opinion).
Time Frame	12 weeks (double blind treatment period)

Outcome Measure Data

Analysis Population Description

The Intent-to-treat (ITT) population was used for the analysis. All randomized patients were included in the analysis in the treatment group to which they were allocated as per randomization.

Arm/Group Title	Placebo	Alfuzosin 0.1 mg/kg/Day	Alfuzosin 0.2 mg/kg/Day
Arm/Group Description	Alfuzosin 0.1 mg/kg/day matching placebo or Alfuzosin 0.2 mg/kg/day matching placebo
Measure Participants	57	57	58
< 40 cmH2O ("Success")	23 40.4%	23 40.4%	28 48.3%
≥ 40 cmH2O or missing ("Failure")	34 59.6%	34 59.6%	30 51.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alfuzosin 0.1 mg/kg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments	P-value was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alfuzosin 0.2 mg/kg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.91
	Comments	P-value was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05.
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Detrusor Leak Point Pressure (LPP)
Description	Detrusor Leak Point Pressure (LPP) was assessed at baseline and 12 weeks as described for the primary outcome measure.
Time Frame	baseline and 12 weeks (double blind treatment period)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Intent-to-treat (ITT) population excluding the patients who didn't have baseline and/or post-baseline LPP values. Patients were included in the treatment group to which they were allocated as per randomization.

Arm/Group Title	Placebo	Alfuzosin 0.1 mg/kg/Day	Alfuzosin 0.2 mg/kg/Day
Arm/Group Description
Measure Participants	54	53	56
Baseline	54.2 (12.6)	53.3 (13.4)	50.9 (10.0)
12 Weeks	48.2 (23.4)	41.6 (18.2)	39.4 (19.5)

3. Secondary Outcome

Title	Absolute Change in Detrusor LPP
Description	Absolute change = Detrusor LPP at 12 weeks - Detrusor LPP at baseline
Time Frame	12 weeks ((double blind treatment period)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the same population as previously (i.e. ITT population excluding the patients who didn't have baseline and/or post-baseline value).

Arm/Group Title	Placebo	Alfuzosin 0.1 mg/kg/Day	Alfuzosin 0.2 mg/kg/Day
Arm/Group Description
Measure Participants	54	53	56
Least Squares Mean (Standard Error) [cmH2O]	-5.4 (2.8)	-11.7 (2.8)	-12.5 (2.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alfuzosin 0.1 mg/kg/Day
	Comments	Change in detrusor LPP was analyzed using a three-way analysis of covariance (ANCOVA) including 3 variables as fixed effects: treatment group (alfuzosin 0.1 mg/kg/day, alfuzosin 0.2 mg/kg/day or placebo), age/formulation group (2-7 years of age on solution, 8-16 years of age on solution or 8-16 years of age on tablets), anticholinergic/antimuscarinic use (yes or no), and using centered baseline detrusor LPP as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1040
	Comments	P-value was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference versus Placebo
	Estimated Value	-6.2
	Confidence Interval	(2-Sided) 95%; -13.72 to 1.29
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.80
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alfuzosin 0.2 mg/kg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1040
	Comments	P-value was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference versus Placebo
	Estimated Value	-7.1
	Confidence Interval	(2-Sided) 95%; -14.51 to 0.39
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.77
	Estimation Comments

4. Secondary Outcome

Title	Relative Change in Detrusor LPP
Description	Relative change = 100 * (Detrusor LPP at 12 weeks - Detrusor LPP at baseline) / Detrusor LPP at baseline
Time Frame	12 weeks (double blind treatment period)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the same population as previously (i.e. ITT population excluding the patients who didn't have baseline and/or post-baseline value).

Arm/Group Title	Placebo	Alfuzosin 0.1 mg/kg/Day	Alfuzosin 0.2 mg/kg/Day
Arm/Group Description
Measure Participants	54	53	56
Least Squares Mean (Standard Error) [percentage of cmH2O]	-9.2 (5.53)	-20.6 (5.56)	-23.5 (5.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alfuzosin 0.1 mg/kg/Day
	Comments	Change in detrusor LPP was analyzed using a three-way analysis of covariance (ANCOVA) including 3 variables as fixed effects: treatment group (alfuzosin 0.1 mg/kg/day, alfuzosin 0.2 mg/kg/day or placebo), age/formulation group (2-7 years of age on solution, 8-16 years of age on solution or 8-16 years of age on tablets), anticholinergic/antimuscarinic use (yes or no), and using centered baseline detrusor LPP as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1338
	Comments	P-values was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference versus Placebo
	Estimated Value	-11.4
	Confidence Interval	(2-Sided) 95%; -26.27 to 3.53
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.54
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alfuzosin 0.2 mg/kg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1152
	Comments	P-value was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference versus Placebo
	Estimated Value	-14.3
	Confidence Interval	(2-Sided) 95%; -29.10 to 0.47
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.48
	Estimation Comments

5. Secondary Outcome

Title	Detrusor Compliance
Description	Detrusor compliance is defined as the relationship between change in detrusor volume and change in detrusor pressure. It was calculated by dividing the volume change (ΔV) by the change in detrusor pressure (Δpdet) during that change in detrusor volume at leak point (C= ΔV/Δpdet).
Time Frame	baseline and 12 weeks (double blind treatment period)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the intent-to-treat (ITT) population excluding the patients who didn't have baseline and/or post baseline detrusor compliance values. Patients were included in the treatment group to which they were allocated as per randomization.

Arm/Group Title	Placebo	Alfuzosin 0.1 mg/kg/Day	Alfuzosin 0.2 mg/kg/Day
Arm/Group Description
Measure Participants	54	52	55
Baseline	3.4 (2.8)	3.4 (2.8)	3.3 (2.5)
12 weeks	4.8 (5.0)	5.3 (4.9)	5.8 (5.9)

6. Secondary Outcome

Title	Relative Change in Detrusor Compliance
Description	Relative change = 100 * (Detrusor compliance at 12 weeks - Detrusor compliance at baseline) / Detrusor compliance at baseline
Time Frame	12 weeks (double blind treatment period)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the same population as previously (i.e. ITT population excluding the patients who didn't have baseline and/or post-baseline value).

Arm/Group Title	Placebo	Alfuzosin 0.1 mg/kg/Day	Alfuzosin 0.2 mg/kg/Day
Arm/Group Description
Measure Participants	54	52	55
Least Squares Mean (Standard Error) [percentage of mL/cmH2O]	113.6 (35.26)	126.6 (35.76)	98.6 (35.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alfuzosin 0.1 mg/kg/Day
	Comments	Change in detrusor compliance was analyzed using a three-way analysis of covariance (ANCOVA) including 3 variables as fixed effects: treatment group (alfuzosin 0.1 mg/kg/day, alfuzosin 0.2 mg/kg/day or placebo), age/formulation group (2-7 years of age on solution, 8-16 years of age on solution or 8-16 years of age on tablets), anticholinergic/antimuscarinic use (yes or no), and using centered baseline detrusor compliance as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7889
	Comments	P-value was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05.
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alfuzosin 0.2 mg/kg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7889
	Comments	P-value was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05.
	Method	ANCOVA
	Comments

7. 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 (double blind treatment period)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the intent-to-treat (ITT) population. All randomized patients were included in the analysis in the treatment group to which they were allocated as per randomization.

Arm/Group Title	Placebo	Alfuzosin 0.1 mg/kg/Day	Alfuzosin 0.2 mg/kg/Day
Arm/Group Description
Measure Participants	57	57	58
No symptomatic UTI	50 87.7%	53 93%	51 87.9%
One symptomatic UTI	5 8.8%	3 5.3%	6 10.3%
Two symptomatic UTI	2 3.5%	1 1.8%	1 1.7%

8. Secondary Outcome

Title	Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes
Description	Symptomatic UTI episodes were assessed similar to the previous outcome measure but for a longer follow-up period.
Time Frame	52 weeks (double blind treatment period + open label extension treatment period)

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). It included 3 + 3 patients treated during the 1st treatment period only, 26 + 28 patients treated during the 2nd treatment period only and 54 + 55 patients treated during both periods.

Arm/Group Title	Alfuzosin 0.1 mg/kg/Day	Alfuzosin 0.2 mg/kg/Day
Arm/Group Description
Measure Participants	83	86
No symptomatic UTI	66 115.8%	70 122.8%
One symptomatic UTI	12 21.1%	13 22.8%
Two symptomatic UTI	3 5.3%	0 0%
Three symptomatic UTI	1 1.8%	1 1.8%
Four symptomatic UTI	1 1.8%	2 3.5%

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 patients who received at least one dose of Alfuzosin, whatever the study period and regardless of the amount of treatment received) 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).
Arm/Group Title	Alfuzosin 0.1 mg/kg/Day		Alfuzosin 0.2 mg/kg/Day
Arm/Group Description
All Cause Mortality
	Alfuzosin 0.1 mg/kg/Day		Alfuzosin 0.2 mg/kg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Alfuzosin 0.1 mg/kg/Day		Alfuzosin 0.2 mg/kg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/83 (12%)		7/86 (8.1%)
Congenital, familial and genetic disorders
ARNOLD-CHIARI MALFORMATION	1/83 (1.2%)		0/86 (0%)
Infections and infestations
VIRAL INFECTION	0/83 (0%)		1/86 (1.2%)
PYELONEPHRITIS	0/83 (0%)		1/86 (1.2%)
PNEUMONIA	1/83 (1.2%)		1/86 (1.2%)
LOBAR PNEUMONIA	1/83 (1.2%)		0/86 (0%)
Injury, poisoning and procedural complications
FEMUR FRACTURE	0/83 (0%)		1/86 (1.2%)
VENTRICULOPERITONEAL SHUNT MALFUNCTION	1/83 (1.2%)		1/86 (1.2%)
CONTUSION	1/83 (1.2%)		0/86 (0%)
Metabolism and nutrition disorders
MALNUTRITION	1/83 (1.2%)		0/86 (0%)
Nervous system disorders
EPILEPSY	2/83 (2.4%)		0/86 (0%)
TETHERED CORD SYNDROME	1/83 (1.2%)		1/86 (1.2%)
Renal and urinary disorders
RENAL IMPAIRMENT	1/83 (1.2%)		0/86 (0%)
URETHRAL HAEMORRHAGE	1/83 (1.2%)		0/86 (0%)
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE	1/83 (1.2%)		0/86 (0%)
TONSILLAR HYPERTROPHY	1/83 (1.2%)		0/86 (0%)
Skin and subcutaneous tissue disorders
DECUBITUS ULCER	0/83 (0%)		2/86 (2.3%)
Other (Not Including Serious) Adverse Events
	Alfuzosin 0.1 mg/kg/Day		Alfuzosin 0.2 mg/kg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/83 (44.6%)		43/86 (50%)
Gastrointestinal disorders
DIARRHOEA	8/83 (9.6%)		10/86 (11.6%)
VOMITING	4/83 (4.8%)		6/86 (7%)
General disorders
PYREXIA	7/83 (8.4%)		10/86 (11.6%)
Infections and infestations
NASOPHARYNGITIS	6/83 (7.2%)		12/86 (14%)
CYSTITIS	5/83 (6%)		9/86 (10.5%)
URINARY TRACT INFECTION	9/83 (10.8%)		6/86 (7%)
PHARYNGITIS	8/83 (9.6%)		5/86 (5.8%)
RESPIRATORY TRACT INFECTION	7/83 (8.4%)		5/86 (5.8%)
UPPER RESPIRATORY TRACT INFECTION	4/83 (4.8%)		5/86 (5.8%)

Limitations/Caveats

[Not Specified]

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 publication, the sponsor shall review the manuscript and can request changes, 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.