The SCOUT Study: "Short Course Therapy for Urinary Tract Infections in Children"

• ClinicalTrials.gov Identifier: NCT01595529
• Recruitment Status: Completed
• First Posted: May 10, 2012
• Results First Posted: July 13, 2020
• Last Update Posted: August 6, 2020
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Urinary Tract Infection
• Interventions: Drug: Cefixime; Drug: Cephalexin; Other: Placebo; Drug: Trimethoprim/Sulfamethoxazole
• Enrollment: 717

Participant Flow

Recruitment Details
Pre-assignment Details	Of the 717 enrolled, 23 did not meet the screening criteria and 1 withdrew consent prior to randomization. 693 subjects were randomized.

Arm/Group Title	Standard Course Treatment	Short Course Treatment
Arm/Group Description	5 days of active therapy to match the physician-initiated therapy, Trimethoprim sulfamethoxazole, Cefixime or Cefdinir or Cephalexin (subjects originally receiving Cefdinir will receive Cefixime) Cefixime: Cefixime 8 mg/kg/day orally, in 1 dose, with a maximum of 400 mg. Subjects originally receiving Cefdinir will receive Cefixime. Cephalexin: Cephalexin 50mg/kg/day in 3 divided doses Trimethoprim/Sulfamethoxazole: 8 mg/kg/day of Trimethoprim-sulfamethoxazole (TMP-SMX) orally in 2 divided doses, with a maximum dose of 160 mg twice a day.	5 days of placebo treatment to match physician-initiated therapy Placebo: Placebo to match the other four active treatments
Period Title: Overall Study
Started [1]	348	345
Treated	337	340
Evaluated for Primary Endpoint, ITT [2]	328	336
ITT Without Treatment Failure [3]	326	322
ITT With Stool Sample at TOC [4]	298	310
Per-protocol, Completed 80% of Dose [5]	308	314
Per-protocol Without Treatment Failure [3]	306	305
Per-protocol With Stool Sample at TOC [4]	280	289
Completed All Milestones	318	318
Completed [6]	324	325
Not Completed	24	20
Reason Not Completed
Adverse Event	2	0
Subject Non-Compliant	2	0
Lost to Follow-up	8	14
Protocol Violation	1	2
Physician Decision	1	0
Consent Withdrawn/Voluntary Withdrawal	3	3
Administrative Decision	1	0
Entry Failure/Screening Failure	6	1
[1] Randomized.; [2] Participants taking at least one dose of treatment from Day 6-10, evaluated at or failed before TOC.; [3] This group was used to evaluate recurrent infection.; [4] This group was used to evaluate colonization with antibiotic-resistant E. coli and K. pneumoniae.; [5] Participants who completed more than 80% of the prescribed dose between Day 6 and Day 10.; [6] A subject could have completed the study without completing all appointments.

Baseline Characteristics

Arm/Group Title		Standard Course Treatment	Short Course Treatment	Total
Arm/Group Description		5 days of active therapy to match the physician-initiated therapy, Trimethoprim sulfamethoxazole, Cefixime or Cefdinir or Cephalexin (subjects originally receiving Cefdinir will receive Cefixime) Cefixime: Cefixime 8 mg/kg/day orally, in 1 dose, with a maximum of 400 mg. Subjects originally receiving Cefdinir will receive Cefixime. Cephalexin: Cephalexin 50mg/kg/day in 3 divided doses Trimethoprim/Sulfamethoxazole: 8 mg/kg/day of Trimethoprim-sulfamethoxazole (TMP-SMX) orally in 2 divided doses, with a maximum dose of 160 mg twice a day.	5 days of placebo treatment to match physician-initiated therapy Placebo: Placebo to match the other four active treatments	Total of all reporting groups
Overall Number of Baseline Participants		328	336	664
Baseline Analysis Population Description		Of the 677 treated patients, only 664 were able to be evaluated for the primary endpoint. Subject noncompliant: 4 Consent withdrawn: 3 Admin/Inv decision: 2 AE concomitant infection: 2 Lost to follow-up: 1 Protocol violation/deviation: 1
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	328 participants	336 participants	664 participants
		4.31 (2.71)	4.16 (2.62)	4.23 (2.66)
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Age	Number Analyzed	328 participants	336 participants	664 participants
	2 months - 35 months	95 29.0%	89 26.5%	184 27.7%
	3 - 6 years	148 45.1%	177 52.7%	325 48.9%
	7 - 10 years	85 25.9%	70 20.8%	155 23.3%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	328 participants	336 participants	664 participants
	Female	316 96.3%	323 96.1%	639 96.2%
	Male	12 3.7%	13 3.9%	25 3.8%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Race	Number Analyzed	328 participants	336 participants	664 participants
	White	217 66.2%	210 62.5%	427 64.3%
	Black/African American	73 22.3%	83 24.7%	156 23.5%
	Asian	5 1.5%	8 2.4%	13 2.0%
	Native Hawaiian/Other Pacific Islander	0 0.0%	2 0.6%	2 0.3%
	American Indian/Alaska Native	0 0.0%	2 0.6%	2 0.3%
	Multi-Racial	23 7.0%	25 7.4%	48 7.2%
	Other	9 2.7%	6 1.8%	15 2.3%
	Unknown	1 0.3%	0 0.0%	1 0.2%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Ethnicity	Number Analyzed	328 participants	336 participants	664 participants
	Hispanic	33 10.1%	27 8.0%	60 9.0%
	Not Hispanic	295 89.9%	309 92.0%	604 91.0%

Outcome Measures

1. Primary Outcome

Title	Comparison of Efficacy Based on Symptomatic Urinary Tract Infection (UTI) Between Short-course and Standard-course of Antibiotics.
Description	A subject will be categorized as a treatment failure, if he/she has a symptomatic UTI in period between Day 6 through the Day 11 - 14 Test of Cure (TOC) Visit: Symptoms Symptoms for all subjects (ages two months to 10 years): fever (a documented temperature of at least 100.4 °F OR 38°C measured anywhere on the body) ,dysuria Additional symptoms for subjects > 2 years of age: suprapubic, abdominal, or flank pain or tenderness OR urinary urgency, frequency, or hesitancy (defined as an increase in these symptoms from pre-diagnosis conditions) Additional symptoms for subjects = 2 months to 2 years of age: poor feeding OR vomiting AND; Pyuria on urinalysis AND; Culture proven infection with a single uropathogen NOTE: As per the above criteria, asymptomatic subjects (including subjects assessed as having asymptomatic bacteriuria) at the Day 11-14 TOC visit will NOT be considered a treatment failure for the primary outcome measure.
Time Frame	Day 11 through Day 14

Outcome Measure Data

Analysis Population Description

Intent to treat population, ITT. All subjects taking at least one dose of study treatment between Day 6 and Day 10 who have been evaluated for treatment success at TOC or have failed prior to TOC.

Arm/Group Title	Standard Course Treatment	Short Course Treatment
Arm/Group Description:	5 days of active therapy to match the physician-initiated therapy, Trimethoprim sulfamethoxazole, Cefixime or Cefdinir or Cephalexin (subjects originally receiving Cefdinir will receive Cefixime) Cefixime: Cefixime 8 mg/kg/day orally, in 1 dose, with a maximum of 400 mg. Subjects originally receiving Cefdinir will receive Cefixime. Cephalexin: Cephalexin 50mg/kg/day in 3 divided doses Trimethoprim/Sulfamethoxazole: 8 mg/kg/day of Trimethoprim-sulfamethoxazole (TMP-SMX) orally in 2 divided doses, with a maximum dose of 160 mg twice a day.	5 days of placebo treatment to match physician-initiated therapy Placebo: Placebo to match the other four active treatments
Overall Number of Participants Analyzed	328	336
Measure Type: Count of Participants; Unit of Measure: Participants
	2 0.6%	14 4.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	The primary analysis was a non-inferiority test comparing the proportion of subjects with symptomatic UTIs at the TOC visit to evaluate whether the difference was within the 5% equivalence interval. This test was conducted by calculating the one-sided 95% upper confidence limit for the difference in symptomatic UTI (treatment failure) rate. If this limit was less than or equal to the equivalence interval (0.05), then would conclude that short course therapy is not inferior to standard therapy.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.035569
	Confidence Interval	(1-Sided) 95%; 0.054844
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Comparison of Efficacy Based on Symptomatic Urinary Tract Infection (UTI) Between Short-course and Standard-course of Antibiotics. Per-protocol Population.
Description	A subject will be categorized as a treatment failure, if he/she has a symptomatic UTI in period between Day 6 through the Day 11 - 14 Test of Cure (TOC) Visit: Symptoms Symptoms for all subjects (ages two months to 10 years): fever (a documented temperature of at least 100.4 °F OR 38°C measured anywhere on the body) ,dysuria Additional symptoms for subjects > 2 years of age: suprapubic, abdominal, or flank pain or tenderness OR urinary urgency, frequency, or hesitancy (defined as an increase in these symptoms from pre-diagnosis conditions) Additional symptoms for subjects = 2 months to 2 years of age: poor feeding OR vomiting AND; Pyuria on urinalysis AND; Culture proven infection with a single uropathogen NOTE: As per the above criteria, asymptomatic subjects (including subjects assessed as having asymptomatic bacteriuria) at the Day 11-14 TOC visit will NOT be considered a treatment failure for the primary outcome measure.
Time Frame	Day 11 through Day 14

Outcome Measure Data

Analysis Population Description

Per-protocol Population (PP): The enrolled subjects who were adherent to their assigned study regimen and completed more than 80% of the prescribed dose between Day 6 and Day 10 (per-protocol population).

Arm/Group Title	Standard Course Treatment	Short Course Treatment
Arm/Group Description:	5 days of active therapy to match the physician-initiated therapy, Trimethoprim sulfamethoxazole, Cefixime or Cefdinir or Cephalexin (subjects originally receiving Cefdinir will receive Cefixime) Cefixime: Cefixime 8 mg/kg/day orally, in 1 dose, with a maximum of 400 mg. Subjects originally receiving Cefdinir will receive Cefixime. Cephalexin: Cephalexin 50mg/kg/day in 3 divided doses Trimethoprim/Sulfamethoxazole: 8 mg/kg/day of Trimethoprim-sulfamethoxazole (TMP-SMX) orally in 2 divided doses, with a maximum dose of 160 mg twice a day.	5 days of placebo treatment to match physician-initiated therapy Placebo: Placebo to match the other four active treatments
Overall Number of Participants Analyzed	308	314
Measure Type: Count of Participants; Unit of Measure: Participants
	2 0.6%	9 2.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	The primary analysis was a non-inferiority test comparing the proportion of subjects with symptomatic UTIs at the TOC visit to evaluate whether the difference was within the 5% equivalence interval. This test was conducted by calculating the one-sided 95% upper confidence limit for the difference in symptomatic UTI (treatment failure) rate. If this limit was less than or equal to the equivalence interval (0.05), then would conclude that short course therapy is not inferior to standard therapy.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.022169
	Confidence Interval	(1-Sided) 95%; 0.03939
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Comparison of Number of Subjects That Have a Recurrent Infection (Includes a Relapse UTI or a Reinfection) Following Short-course Versus Standard-course of Antibiotics.
Description	[Not Specified]
Time Frame	Day 11 through Day 44

Outcome Measure Data

Analysis Population Description

Subjects in the ITT population who did not experience a treatment failure.

Arm/Group Title	Standard Course Treatment	Short Course Treatment
Arm/Group Description:	5 days of active therapy to match the physician-initiated therapy, Trimethoprim sulfamethoxazole, Cefixime or Cefdinir or Cephalexin (subjects originally receiving Cefdinir will receive Cefixime) Cefixime: Cefixime 8 mg/kg/day orally, in 1 dose, with a maximum of 400 mg. Subjects originally receiving Cefdinir will receive Cefixime. Cephalexin: Cephalexin 50mg/kg/day in 3 divided doses Trimethoprim/Sulfamethoxazole: 8 mg/kg/day of Trimethoprim-sulfamethoxazole (TMP-SMX) orally in 2 divided doses, with a maximum dose of 160 mg twice a day.	5 days of placebo treatment to match physician-initiated therapy Placebo: Placebo to match the other four active treatments
Overall Number of Participants Analyzed	326	322
Measure Type: Count of Participants; Unit of Measure: Participants
	12 3.7%	13 4.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.00356
	Confidence Interval	(2-Sided) 95%; -0.03323 to 0.026102
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Comparison of Number of Subjects That Have a Recurrent Infection (Includes a Relapse UTI or a Reinfection) Following Short-course Versus Standard-course of Antibiotics. Per-protocol Population.
Description	[Not Specified]
Time Frame	Day 11 through Day 44

Outcome Measure Data

Analysis Population Description

Subjects in the per-protocol population who did not experience a treatment failure.

Arm/Group Title	Standard Course Treatment	Short Course Treatment
Arm/Group Description:	5 days of active therapy to match the physician-initiated therapy, Trimethoprim sulfamethoxazole, Cefixime or Cefdinir or Cephalexin (subjects originally receiving Cefdinir will receive Cefixime) Cefixime: Cefixime 8 mg/kg/day orally, in 1 dose, with a maximum of 400 mg. Subjects originally receiving Cefdinir will receive Cefixime. Cephalexin: Cephalexin 50mg/kg/day in 3 divided doses Trimethoprim/Sulfamethoxazole: 8 mg/kg/day of Trimethoprim-sulfamethoxazole (TMP-SMX) orally in 2 divided doses, with a maximum dose of 160 mg twice a day.	5 days of placebo treatment to match physician-initiated therapy Placebo: Placebo to match the other four active treatments
Overall Number of Participants Analyzed	306	305
Measure Type: Count of Participants; Unit of Measure: Participants
	10 3.3%	13 4.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.00994
	Confidence Interval	(2-Sided) 95%; -0.04012 to 0.020236
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Comparison of the Number of Subjects That Become Colonized With Antimicrobial Resistant Escherichia Coli (E. Coli) and Klebsiella Pneumoniae (K. Pneumoniae) in the Gastrointestinal Tract Following Short-course Versus Standard Course of Antibiotics.
Description	A child would have emergent antibiotic resistance if they: Had no antibiotic-resistant E.coli or K.pneumoniae at enrollment but one or both are now present. OR; Had either antibiotic-resistant E.coli or K.pneumoniae at enrollment but now the other antibiotic-resistant organism is present OR; Had antibiotic-resistant E.coli and/or K.pneumoniae at enrollment, but have now developed resistance to new antibiotics in either organism.
Time Frame	Day 11 through Day 30

Outcome Measure Data

Analysis Population Description

Subjects in the ITT population who have a stool sample at TOC visit. Some treatment failures will not have a sample collected at TOC because they failed prior to TOC. Treatment failures without the sample at TOC are excluded.

Arm/Group Title	Standard Course Treatment	Short Course Treatment
Arm/Group Description:	5 days of active therapy to match the physician-initiated therapy, Trimethoprim sulfamethoxazole, Cefixime or Cefdinir or Cephalexin (subjects originally receiving Cefdinir will receive Cefixime) Cefixime: Cefixime 8 mg/kg/day orally, in 1 dose, with a maximum of 400 mg. Subjects originally receiving Cefdinir will receive Cefixime. Cephalexin: Cephalexin 50mg/kg/day in 3 divided doses Trimethoprim/Sulfamethoxazole: 8 mg/kg/day of Trimethoprim-sulfamethoxazole (TMP-SMX) orally in 2 divided doses, with a maximum dose of 160 mg twice a day.	5 days of placebo treatment to match physician-initiated therapy Placebo: Placebo to match the other four active treatments
Overall Number of Participants Analyzed	298	310
Measure Type: Count of Participants; Unit of Measure: Participants
Test of Cure Visit (Day 11-14)	22 7.4%	31 10.0%
Outcome Assessment Visit (Day 24-30)	23 7.7%	28 9.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments	At Test of Cure Visit
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2282
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments	At Outcome Assessment Visit
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4876
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

6. Secondary Outcome

Title	Comparison of the Number of Subjects That Become Colonized With Antimicrobial Resistant E. Coli and K. Pneumoniae in the Gastrointestinal Tract Following Short-course Versus Standard Course of Antibiotics. Per-protocol Population.
Description	A child would have emergent antibiotic resistance if they: Had no antibiotic-resistant E.coli or K.pneumoniae at enrollment but one or both are now present. OR; Had either antibiotic-resistant E.coli or K.pneumoniae at enrollment but now the other antibiotic-resistant organism is present OR; Had antibiotic-resistant E.coli and/or K.pneumoniae at enrollment, but have now developed resistance to new antibiotics in either organism.
Time Frame	Day 11 through Day 30

Outcome Measure Data

Analysis Population Description

Subjects in the ITT population who have a stool sample at TOC visit. Some treatment failures will not have a sample collected at TOC because they failed prior to TOC. Treatment failures without the sample at TOC would be excluded from the Antibiotic Resistant ITT population.

Arm/Group Title	Standard Course Treatment	Short Course Treatment
Arm/Group Description:	5 days of active therapy to match the physician-initiated therapy, Trimethoprim sulfamethoxazole, Cefixime or Cefdinir or Cephalexin (subjects originally receiving Cefdinir will receive Cefixime) Cefixime: Cefixime 8 mg/kg/day orally, in 1 dose, with a maximum of 400 mg. Subjects originally receiving Cefdinir will receive Cefixime. Cephalexin: Cephalexin 50mg/kg/day in 3 divided doses Trimethoprim/Sulfamethoxazole: 8 mg/kg/day of Trimethoprim-sulfamethoxazole (TMP-SMX) orally in 2 divided doses, with a maximum dose of 160 mg twice a day.	5 days of placebo treatment to match physician-initiated therapy Placebo: Placebo to match the other four active treatments
Overall Number of Participants Analyzed	280	289
Measure Type: Count of Participants; Unit of Measure: Participants
Test of Cure Visit (Day 11-14)	22 7.9%	28 9.7%
Outcome Assessment Visit (Day 24-30)	23 8.2%	23 8.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments	At Test of Cure Visit
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4184
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments	At Outcome Assessment Visit
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9782
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

7. Secondary Outcome

Title	Comparison of the Number of Subjects With Asymptomatic Bacteriuria Following Short-course Versus Standard-course of Antibiotics.
Description	Asymptomatic Bacteriuria is defined in any SCOUT subject by: Absence of symptoms attributable to UTI including fever AND/OR the following: Symptoms for all children (ages two months to 10 years): fever (a documented temperature of at least 100.4 °F OR 38°C measured anywhere on the body) dysuria Additional symptoms for children > 2 years of age: suprapubic, abdominal, or flank pain or tenderness OR urinary urgency, frequency, or hesitancy (defined as an increase in these symptoms from pre-diagnosis conditions) Additional symptoms for children = 2 months to 2 years of age: poor feeding OR vomiting AND; A positive urine culture 5 x 104 CFU/mL (catheterized or suprapubic aspiration urine specimen) OR >105 CFU/mL (clean void specimen).
Time Frame	Day 11 through Day 14

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) Population: All subjects taking at least one dose of study treatment between Day 6 and Day 10 who have been evaluated for treatment success at TOC or have failed prior to TOC.

Arm/Group Title	Standard Course Treatment	Short Course Treatment
Arm/Group Description:	5 days of active therapy to match the physician-initiated therapy, Trimethoprim sulfamethoxazole, Cefixime or Cefdinir or Cephalexin (subjects originally receiving Cefdinir will receive Cefixime) Cefixime: Cefixime 8 mg/kg/day orally, in 1 dose, with a maximum of 400 mg. Subjects originally receiving Cefdinir will receive Cefixime. Cephalexin: Cephalexin 50mg/kg/day in 3 divided doses Trimethoprim/Sulfamethoxazole: 8 mg/kg/day of Trimethoprim-sulfamethoxazole (TMP-SMX) orally in 2 divided doses, with a maximum dose of 160 mg twice a day.	5 days of placebo treatment to match physician-initiated therapy Placebo: Placebo to match the other four active treatments
Overall Number of Participants Analyzed	328	336
Measure Type: Count of Participants; Unit of Measure: Participants
	11 3.4%	29 8.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.05277
	Confidence Interval	(2-Sided) 95%; -0.08857 to -0.01698
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Comparison of the Number of Subjects With Asymptomatic Bacteriuria Following Short-course Versus Standard-course of Antibiotics. Per-protocol Population.
Description	Asymptomatic Bacteriuria is defined in any SCOUT subject by: Absence of symptoms attributable to UTI including fever AND/OR the following: Symptoms for all children (ages two months to 10 years): fever (a documented temperature of at least 100.4 °F OR 38°C measured anywhere on the body) dysuria Additional symptoms for children > 2 years of age: suprapubic, abdominal, or flank pain or tenderness OR urinary urgency, frequency, or hesitancy (defined as an increase in these symptoms from pre-diagnosis conditions) Additional symptoms for children = 2 months to 2 years of age: poor feeding OR vomiting AND; A positive urine culture 5 x 104 CFU/mL (catheterized or suprapubic aspiration urine specimen) OR >105 CFU/mL (clean void specimen).
Time Frame	Day 11 through Day 14

Outcome Measure Data

Analysis Population Description

Per-protocol Population (PP): The enrolled subjects who were adherent to their assigned study regimen and completed more than 80% of the prescribed dose between Day 6 and Day 10 (per-protocol population).

Arm/Group Title	Standard Course Treatment	Short Course Treatment
Arm/Group Description:	5 days of active therapy to match the physician-initiated therapy, Trimethoprim sulfamethoxazole, Cefixime or Cefdinir or Cephalexin (subjects originally receiving Cefdinir will receive Cefixime) Cefixime: Cefixime 8 mg/kg/day orally, in 1 dose, with a maximum of 400 mg. Subjects originally receiving Cefdinir will receive Cefixime. Cephalexin: Cephalexin 50mg/kg/day in 3 divided doses Trimethoprim/Sulfamethoxazole: 8 mg/kg/day of Trimethoprim-sulfamethoxazole (TMP-SMX) orally in 2 divided doses, with a maximum dose of 160 mg twice a day.	5 days of placebo treatment to match physician-initiated therapy Placebo: Placebo to match the other four active treatments
Overall Number of Participants Analyzed	308	314
Measure Type: Count of Participants; Unit of Measure: Participants
	11 3.6%	29 9.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.05664
	Confidence Interval	(2-Sided) 95%; -0.09479 to -0.01850
	Estimation Comments	[Not Specified]

9. Secondary Outcome

Title	Comparison of the Number of Subjects With Clinical Symptoms That May be Related to a UTI Following Short-course Versus Standard-course of Antibiotics.
Description	[Not Specified]
Time Frame	Up to Day 14

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) Population: All subjects taking at least one dose of study treatment between Day 6 and Day 10 who have been evaluated for treatment success at TOC or have failed prior to TOC.

Arm/Group Title	Standard Course Treatment	Short Course Treatment
Arm/Group Description:	5 days of active therapy to match the physician-initiated therapy, Trimethoprim sulfamethoxazole, Cefixime or Cefdinir or Cephalexin (subjects originally receiving Cefdinir will receive Cefixime) Cefixime: Cefixime 8 mg/kg/day orally, in 1 dose, with a maximum of 400 mg. Subjects originally receiving Cefdinir will receive Cefixime. Cephalexin: Cephalexin 50mg/kg/day in 3 divided doses Trimethoprim/Sulfamethoxazole: 8 mg/kg/day of Trimethoprim-sulfamethoxazole (TMP-SMX) orally in 2 divided doses, with a maximum dose of 160 mg twice a day.	5 days of placebo treatment to match physician-initiated therapy Placebo: Placebo to match the other four active treatments
Overall Number of Participants Analyzed	328	336
Measure Type: Count of Participants; Unit of Measure: Participants
	30 9.1%	41 12.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.03056
	Confidence Interval	(2-Sided) 95%; -0.07744 to 0.016323
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	Comparison of the Number of Subjects With Clinical Symptoms That May be Related to a UTI Following Short-course Versus Standard-course of Antibiotics. Per-protocol Population
Description	[Not Specified]
Time Frame	Up to Day 14

Outcome Measure Data

Analysis Population Description

Per-protocol Population (PP): The enrolled subjects who were adherent to their assigned study regimen and completed more than 80% of the prescribed dose between Day 6 and Day 10 (per-protocol population).

Arm/Group Title	Standard Course Treatment	Short Course Treatment
Arm/Group Description:	5 days of active therapy to match the physician-initiated therapy, Trimethoprim sulfamethoxazole, Cefixime or Cefdinir or Cephalexin (subjects originally receiving Cefdinir will receive Cefixime) Cefixime: Cefixime 8 mg/kg/day orally, in 1 dose, with a maximum of 400 mg. Subjects originally receiving Cefdinir will receive Cefixime. Cephalexin: Cephalexin 50mg/kg/day in 3 divided doses Trimethoprim/Sulfamethoxazole: 8 mg/kg/day of Trimethoprim-sulfamethoxazole (TMP-SMX) orally in 2 divided doses, with a maximum dose of 160 mg twice a day.	5 days of placebo treatment to match physician-initiated therapy Placebo: Placebo to match the other four active treatments
Overall Number of Participants Analyzed	308	314
Measure Type: Count of Participants; Unit of Measure: Participants
	29 9.4%	33 10.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.01094
	Confidence Interval	(2-Sided) 95%; -0.0580 to 0.036117
	Estimation Comments	[Not Specified]

11. Secondary Outcome

Title	Comparison of the Number of Subjects With Positive Urine Cultures Following Short-course Versus Standard-course of Antibiotics.
Description	[Not Specified]
Time Frame	Up to Day 14

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) Population: All subjects taking at least one dose of study treatment between Day 6 and Day 10 who have been evaluated for treatment success at TOC or have failed prior to TOC.

Arm/Group Title	Standard Course Treatment	Short Course Treatment
Arm/Group Description:	5 days of active therapy to match the physician-initiated therapy, Trimethoprim sulfamethoxazole, Cefixime or Cefdinir or Cephalexin (subjects originally receiving Cefdinir will receive Cefixime) Cefixime: Cefixime 8 mg/kg/day orally, in 1 dose, with a maximum of 400 mg. Subjects originally receiving Cefdinir will receive Cefixime. Cephalexin: Cephalexin 50mg/kg/day in 3 divided doses Trimethoprim/Sulfamethoxazole: 8 mg/kg/day of Trimethoprim-sulfamethoxazole (TMP-SMX) orally in 2 divided doses, with a maximum dose of 160 mg twice a day.	5 days of placebo treatment to match physician-initiated therapy Placebo: Placebo to match the other four active treatments
Overall Number of Participants Analyzed	328	336
Measure Type: Count of Participants; Unit of Measure: Participants
	6 1.8%	41 12.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.10373
	Confidence Interval	(2-Sided) 95%; -0.14161 to -0.06585
	Estimation Comments	[Not Specified]

12. Secondary Outcome

Title	Comparison of the Number of Subjects With Positive Urine Cultures Following Short-course Versus Standard-course of Antibiotics. Per-protocol Population.
Description	[Not Specified]
Time Frame	Up to Day 14

Outcome Measure Data

Analysis Population Description

Per-protocol Population (PP): The enrolled subjects who were adherent to their assigned study regimen and completed more than 80% of the prescribed dose between Day 6 and Day 10 (per-protocol population).

Arm/Group Title	Standard Course Treatment	Short Course Treatment
Arm/Group Description:	5 days of active therapy to match the physician-initiated therapy, Trimethoprim sulfamethoxazole, Cefixime or Cefdinir or Cephalexin (subjects originally receiving Cefdinir will receive Cefixime) Cefixime: Cefixime 8 mg/kg/day orally, in 1 dose, with a maximum of 400 mg. Subjects originally receiving Cefdinir will receive Cefixime. Cephalexin: Cephalexin 50mg/kg/day in 3 divided doses Trimethoprim/Sulfamethoxazole: 8 mg/kg/day of Trimethoprim-sulfamethoxazole (TMP-SMX) orally in 2 divided doses, with a maximum dose of 160 mg twice a day.	5 days of placebo treatment to match physician-initiated therapy Placebo: Placebo to match the other four active treatments
Overall Number of Participants Analyzed	308	314
Measure Type: Count of Participants; Unit of Measure: Participants
	6 1.9%	35 11.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.09198
	Confidence Interval	(2-Sided) 95%; -0.13006 to -0.05391
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Day 6 to Day 44 Follow-up Phone Call
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Standard Course Treatment		Short Course Treatment
Arm/Group Description	5 days of active therapy to match the physician-initiated therapy, Trimethoprim sulfamethoxazole, Cefixime or Cefdinir or Cephalexin (subjects originally receiving Cefdinir will receive Cefixime) Cefixime: Cefixime 8 mg/kg/day orally, in 1 dose, with a maximum of 400 mg. Subjects originally receiving Cefdinir will receive Cefixime. Cephalexin: Cephalexin 50mg/kg/day in 3 divided doses Trimethoprim/Sulfamethoxazole: 8 mg/kg/day of Trimethoprim-sulfamethoxazole (TMP-SMX) orally in 2 divided doses, with a maximum dose of 160 mg twice a day.		5 days of placebo treatment to match physician-initiated therapy Placebo: Placebo to match the other four active treatments
All-Cause Mortality
	Standard Course Treatment		Short Course Treatment
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/328 (0.00%)		0/336 (0.00%)
Serious Adverse Events
	Standard Course Treatment		Short Course Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/328 (0.61%)		4/336 (1.19%)
Congenital, familial and genetic disorders
URETHRAL VALVES † 1	0/328 (0.00%)	0	1/336 (0.30%)	1
General disorders
PYREXIA † 1	1/328 (0.30%)	1	1/336 (0.30%)	1
Infections and infestations
PYELONEPHRITIS † 1	0/328 (0.00%)	0	1/336 (0.30%)	1
Injury, poisoning and procedural complications
HUMERUS FRACTURE † 1	1/328 (0.30%)	1	0/336 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
ASTHMA † 1	0/328 (0.00%)	0	1/336 (0.30%)	1
1 Term from vocabulary, MedDRA (Unspecified); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	1%
	Standard Course Treatment		Short Course Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	155/328 (47.26%)		147/336 (43.75%)
Gastrointestinal disorders
DIARRHOEA † 1	42/328 (12.80%)		34/336 (10.12%)
VOMITING † 1	11/328 (3.35%)		20/336 (5.95%)
CONSTIPATION † 1	8/328 (2.44%)		7/336 (2.08%)
ABDOMINAL PAIN † 1	3/328 (0.91%)		5/336 (1.49%)
TEETHING † 1	1/328 (0.30%)		4/336 (1.19%)
General disorders
PYREXIA † 1	15/328 (4.57%)		18/336 (5.36%)
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION † 1	10/328 (3.05%)		10/336 (2.98%)
VIRAL INFECTION † 1	1/328 (0.30%)		4/336 (1.19%)
GASTROENERITIS † 1	4/328 (1.22%)		0/336 (0.00%)
NASOPHARYNGITIS † 1	2/328 (0.61%)		5/336 (1.49%)
OTITIS MEDIA ACUTE † 1	5/328 (1.52%)		3/336 (0.89%)
Respiratory, thoracic and mediastinal disorders
RHINORRHOEA † 1	12/328 (3.66%)		16/336 (4.76%)
COUGH † 1	21/328 (6.40%)		23/336 (6.85%)
OROPHARYNGEAL PAIN † 1	7/328 (2.13%)		5/336 (1.49%)
RESPIRATORY DISORDER † 1	4/328 (1.22%)		4/336 (1.19%)
NASAL CONGESTION † 1	1/328 (0.30%)		4/336 (1.19%)
Skin and subcutaneous tissue disorders
DERMATITIS DIAPER † 1	10/328 (3.05%)		12/336 (3.57%)
RASH † 1	11/328 (3.35%)		12/336 (3.57%)
1 Term from vocabulary, MedDRA (Unspecified); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Elizabeth Rowley
• Organization: Westat
• Phone: (919) 941-8325
• EMail: ElizabethRowley@westat.com

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT01595529
• Other Study ID Numbers: 09-0103
• First Submitted: May 8, 2012
• First Posted: May 10, 2012
• Results First Submitted: June 25, 2020
• Results First Posted: July 13, 2020
• Last Update Posted: August 6, 2020