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

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01595529
• Collaborator: (none)
• Enrollment: 717
• Location: 1
• Arms: 2
• Actual Duration (Months): 86.8
• Patients Per Site Per Month: 8.3

Study Details

Study Description

Brief Summary

The SCOUT study is a multi-center, centrally randomized, double-blind, placebo-controlled non-inferiority clinical trial. 746 participants will be enrolled over a 4.5 year period. 672 will be evaluated for the study's primary outcome measure. After the first 5 days of primary care physician initiated antimicrobial therapy, patients who are afebrile and asymptomatic will then be randomized (1:1) to the standard course therapy arm of 5 more days of the same antibiotic therapy or the short course therapy arm of a placebo for 5 more days (for 10 days total). The primary objective of this study is to determine if halting antimicrobial therapy in subjects who have exhibited clinical improvement 5 days after starting antibiotic therapy (short course therapy) have the same failure rate (symptomatic UTI) through visit Day 11-14 as subjects who continue to take antibiotics for an additional 5 days (standard course therapy).

Condition or Disease	Intervention/Treatment	Phase
Urinary Tract Infection	Drug: Cefixime; Drug: Cephalexin; Other: Placebo; Drug: Trimethoprim/Sulfamethoxazole	Phase 2

Detailed Description

The SCOUT Study is a multi-center, centrally randomized, double-blind, placebo-controlled non-inferiority clinical trial of 746 children ages two months (at least 36 weeks gestation from birth for subjects < two years of age) to 10 years with a confirmed diagnosis of a urinary tract infection (UTI) to evaluate 672 for the study's primary outcome measure. UTI is one of the most common serious bacterial infections during childhood. Escherichia coli (E. coli) isolates account for 80-90 percent of all outpatient UTIs in children. Although antibiotics are the first treatment choice for urinary tract infections, antibiotic-resistant strains of E. coli, the most common cause of UTIs, are increasing worldwide. The study will enroll 746 children who have demonstrated clinical improvement five days after starting the originally prescribed antibiotic (afebrile and asymptomatic) and they will be randomized either to the standard-course arm or the short-course arm at a 1:1 ratio. Subjects will be enrolled over approximately a four and a half year period. Study duration for each individual subject will be approximately five weeks. The study product will consist of trimethoprim-sulfamethoxazole (TMP-SMX), cefixime, cefdinir, cephalexin and the corresponding placebos. The primary objective of this study is to determine if halting antimicrobial therapy in subjects who have exhibited clinical improvement 5 days after starting antibiotic therapy (short course therapy) have the same failure rate (symptomatic UTI) through visit Day 11-14 as subjects who continue to take antibiotics for an additional 5 days (standard course therapy). The secondary objectives are: 1) to determine if short-course therapy compared to standard course therapy results in similar numbers of children experiencing a recurrent urinary tract infection (relapse and reinfection; 2) to determine if short-course therapy compared to standard course therapy results in similar numbers of children with asymptomatic bacteriuria; 3) to determine if short-course therapy compared to standard course therapy results in similar numbers of children with gastrointestinal colonization of antimicrobial resistant Escherichia coli (E. coli) and Klebsiella pneumonia (K. pneumoniae); 4) to determine if short-course therapy compared to standard course therapy results in similar numbers of subjects presenting with clinical symptoms that may be related to UTI; 5) to determine if the number of subjects with positive urine culture prior to or at visit Day 11-14 is similar after short-course therapy compared to standard course therapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 717 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Targeted Clinical Trials to Reduce the Risk of Antimicrobial Resistance The SCOUT Study: "Short Course Therapy for Urinary Tract Infections in Children"
• Actual Study Start Date: May 18, 2012
• Actual Primary Completion Date: Jun 30, 2019
• Actual Study Completion Date: Aug 12, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active treatment 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)	Drug: Cefixime; Cefixime 8 mg/kg/day orally, in 1 dose, with a maximum of 400 mg. Subjects originally receiving Cefdinir will receive Cefixime.; Drug: Cephalexin; Cephalexin 50mg/kg/day in 3 divided doses; Drug: 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.
Placebo Comparator: Placebo treatment 5 days of placebo treatment to match physician-initiated therapy	Other: Placebo; Placebo to match the other four active treatments

Outcome Measures

Primary Outcome Measures

1. Comparison of Efficacy Based on Symptomatic Urinary Tract Infection (UTI) Between Short-course and Standard-course of Antibiotics. [Day 11 through Day 14]

   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.

2. Comparison of Efficacy Based on Symptomatic Urinary Tract Infection (UTI) Between Short-course and Standard-course of Antibiotics. Per-protocol Population. [Day 11 through Day 14]

   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.

Secondary Outcome Measures

1. 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. [Day 11 through Day 44]

2. 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. [Day 11 through Day 44]

3. 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. [Day 11 through Day 30]

   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.

4. 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. [Day 11 through Day 30]

   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.

5. Comparison of the Number of Subjects With Asymptomatic Bacteriuria Following Short-course Versus Standard-course of Antibiotics. [Day 11 through Day 14]

   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).

6. Comparison of the Number of Subjects With Asymptomatic Bacteriuria Following Short-course Versus Standard-course of Antibiotics. Per-protocol Population. [Day 11 through Day 14]

   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).

7. Comparison of the Number of Subjects With Clinical Symptoms That May be Related to a UTI Following Short-course Versus Standard-course of Antibiotics. [Up to Day 14]

8. 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 [Up to Day 14]

9. Comparison of the Number of Subjects With Positive Urine Cultures Following Short-course Versus Standard-course of Antibiotics. [Up to Day 14]

10. Comparison of the Number of Subjects With Positive Urine Cultures Following Short-course Versus Standard-course of Antibiotics. Per-protocol Population. [Up to Day 14]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Months to 10 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age at randomization: at least two months (at least 36 weeks gestational age for subjects less than two years of age) to 10 years of age (120 months).

2. Confirmed UTI (Urinary Tract Infection) diagnosis.

3. Documented Clinical Improvement at Randomization.

4. Afebrile: No documented temperature > / = 100.4 degrees Fahrenheit or 38 degrees Celsius (measured anywhere on the body) 24 hours prior to the enrollment visit

5. Asymptomatic: report NONE of the following symptoms:

• Symptoms for all children (ages two months to 10 years):

• Fever (a documented temperature of at least 100.4 degrees Fahrenheit OR 38 degrees Celsius 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

1. Only children who have been prescribed one of the four antibiotics for which a placebo is available will be eligible to participate.

• TMP-SMX; Cefixime; Cefdinir or Cephalexin. (Note a child that received a one-time dose of I.M. or I.V. medication (i.e. in ER or clinic) prior to starting on the one of the four oral medications is eligible for enrollment)

1. Parental or guardian permission (informed consent) and if appropriate, child assent (if > / = seven years of age).

Exclusion Criteria:

1. A urine culture proven infection with a second uropathogen > 10,000 CFU/mL collected via suprapubic aspiration or catheter or > 50,000 CFU/mL collected via clean void.

2. A child hospitalized with a UTI that has the following: concomitant bacteremia associated with the UTI, urosepsis, or is in intensive care.

3. A child whose urine culture reveals an organism that is resistant to the initially prescribed antibiotic.

4. A child with a catheter-associated UTI.

5. A child with known anaphylactic allergies to the study products.

6. A child with phenylketonuria (PKU).

7. A child diagnosed with congenital anomalies of the genitourinary tract.

8. UTI in children with known anatomic abnormalities of the genitourinary tract other than VUR (Vesicoureteral reflux), duplicated collection systems, and hydronephrosis.

9. A child that is not able to take oral medications.

10. Previous surgery of the genitourinary tract (except circumcision in male children).

11. Presence of an immunocompromising condition (e.g., HIV, malignancy, solid-organ transplant recipients, use of chronic corticosteroids or other immunosuppressive agents).

12. Unlikely to complete follow-up (e.g. not available for the two follow-up study visits and the follow-up phone call).

13. A child with a known history of type I hypersensitivity of the study antibiotics to be prescribed .

14. Enrollment in another antibiotic study less than 30 days prior to enrollment visit.

15. Previous enrollment of individuals in this study.

16. Planned enrollment during this study coincides with enrollment in another therapeutic drug study (excluding vaccine).

17. A child with a history of UTI within the past 30 days.

18. A child with known Grade III-V VUR.

19. A child taking antibiotic prophylaxis for any reason.

20. A child who has started Day 6 of the originally prescribed antibiotic treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Pittsburgh of UPMC - General Academic Pediatric	Pittsburgh	Pennsylvania	United States	15213-3205

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Sep 20, 2018
• Statistical Analysis Plan - Feb 25, 2020

More Information

Publications

None provided.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT01595529
• Other Study ID Numbers: 09-0103
• First Posted: May 10, 2012
• Last Update Posted: Aug 6, 2020
• Last Verified: Oct 22, 2013

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): antibiotic therapy; antimicrobial resistance; children; E.coli; K.pneumoniae; parent study; SCOUT Study; spectrum stool bacteria; stool culture; urinary tract infections
• Additional relevant MeSH terms: Infections; Communicable Diseases; Urinary Tract Infections; Trimethoprim; Sulfamethoxazole; Cephalexin; Cefixime

Study Results

Participant Flow

Pre-assignment Detail	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	348	345
Treated	337	340
Evaluated for Primary Endpoint, ITT	328	336
ITT Without Treatment Failure	326	322
ITT With Stool Sample at TOC	298	310
Per-protocol, Completed 80% of Dose	308	314
Per-protocol Without Treatment Failure	306	305
Per-protocol With Stool Sample at TOC	280	289
Completed All Milestones	318	318
COMPLETED	324	325
NOT COMPLETED	24	20

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 Participants	328	336	664
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	4.31 (2.71)	4.16 (2.62)	4.23 (2.66)
Age, Customized (Count of Participants)
2 months - 35 months	95 29%	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 (Count of Participants)
Female	316 96.3%	323 96.1%	639 96.2%
Male	12 3.7%	13 3.9%	25 3.8%
Race/Ethnicity, Customized (Count of 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%
Native Hawaiian/Other Pacific Islander	0 0%	2 0.6%	2 0.3%
American Indian/Alaska Native	0 0%	2 0.6%	2 0.3%
Multi-Racial	23 7%	25 7.4%	48 7.2%
Other	9 2.7%	6 1.8%	15 2.3%
Unknown	1 0.3%	0 0%	1 0.2%
Race/Ethnicity, Customized (Count of Participants)
Hispanic	33 10.1%	27 8%	60 9%
Not Hispanic	295 89.9%	309 92%	604 91%

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
Measure Participants	328	336
Count of Participants [Participants]	2 0.6%	14 4.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments
	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.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.035569
	Confidence Interval	(1-Sided) 95%; to 0.054844
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Measure Participants	308	314
Count of Participants [Participants]	2 0.6%	9 2.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments
	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.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.022169
	Confidence Interval	(1-Sided) 95%; to 0.03939
	Parameter Dispersion	Type: Value:
	Estimation Comments

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.
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
Measure Participants	326	322
Count of Participants [Participants]	12 3.7%	13 3.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.00356
	Confidence Interval	(2-Sided) 95%; -0.03323 to 0.026102
	Parameter Dispersion	Type: Value:
	Estimation Comments

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.
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
Measure Participants	306	305
Count of Participants [Participants]	10 3%	13 3.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.00994
	Confidence Interval	(2-Sided) 95%; -0.04012 to 0.020236
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Measure Participants	298	310
Test of Cure Visit (Day 11-14)	22 6.7%	31 9.2%
Outcome Assessment Visit (Day 24-30)	23 7%	28 8.3%

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
Statistical Test of Hypothesis	p-Value	0.2282
	Comments
	Method	Chi-squared
	Comments

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
Statistical Test of Hypothesis	p-Value	0.4876
	Comments
	Method	Chi-squared
	Comments

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
Measure Participants	280	289
Test of Cure Visit (Day 11-14)	22 6.7%	28 8.3%
Outcome Assessment Visit (Day 24-30)	23 7%	23 6.8%

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
Statistical Test of Hypothesis	p-Value	0.4184
	Comments
	Method	Chi-squared
	Comments

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
Statistical Test of Hypothesis	p-Value	0.9782
	Comments
	Method	Chi-squared
	Comments

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
Measure Participants	328	336
Count of Participants [Participants]	11 3.4%	29 8.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.05277
	Confidence Interval	(2-Sided) 95%; -0.08857 to -0.01698
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Measure Participants	308	314
Count of Participants [Participants]	11 3.4%	29 8.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.05664
	Confidence Interval	(2-Sided) 95%; -0.09479 to -0.01850
	Parameter Dispersion	Type: Value:
	Estimation Comments

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.
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
Measure Participants	328	336
Count of Participants [Participants]	30 9.1%	41 12.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.03056
	Confidence Interval	(2-Sided) 95%; -0.07744 to 0.016323
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
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
Measure Participants	308	314
Count of Participants [Participants]	29 8.8%	33 9.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.01094
	Confidence Interval	(2-Sided) 95%; -0.0580 to 0.036117
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Comparison of the Number of Subjects With Positive Urine Cultures Following Short-course Versus Standard-course of Antibiotics.
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
Measure Participants	328	336
Count of Participants [Participants]	6 1.8%	41 12.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.10373
	Confidence Interval	(2-Sided) 95%; -0.14161 to -0.06585
	Parameter Dispersion	Type: Value:
	Estimation Comments

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.
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
Measure Participants	308	314
Count of Participants [Participants]	6 1.8%	35 10.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Course Treatment, Short Course Treatment
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.09198
	Confidence Interval	(2-Sided) 95%; -0.13006 to -0.05391
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Day 6 to Day 44 Follow-up Phone Call
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	0/328 (0%)		0/336 (0%)
Serious Adverse Events
	Standard Course Treatment		Short Course Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/328 (0.6%)		4/336 (1.2%)
Congenital, familial and genetic disorders
URETHRAL VALVES	0/328 (0%)	0	1/336 (0.3%)	1
General disorders
PYREXIA	1/328 (0.3%)	1	1/336 (0.3%)	1
Infections and infestations
PYELONEPHRITIS	0/328 (0%)	0	1/336 (0.3%)	1
Injury, poisoning and procedural complications
HUMERUS FRACTURE	1/328 (0.3%)	1	0/336 (0%)	0
Respiratory, thoracic and mediastinal disorders
ASTHMA	0/328 (0%)	0	1/336 (0.3%)	1
Other (Not Including Serious) Adverse Events
	Standard Course Treatment		Short Course Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	155/328 (47.3%)		147/336 (43.8%)
Gastrointestinal disorders
DIARRHOEA	42/328 (12.8%)		34/336 (10.1%)
VOMITING	11/328 (3.4%)		20/336 (6%)
CONSTIPATION	8/328 (2.4%)		7/336 (2.1%)
ABDOMINAL PAIN	3/328 (0.9%)		5/336 (1.5%)
TEETHING	1/328 (0.3%)		4/336 (1.2%)
General disorders
PYREXIA	15/328 (4.6%)		18/336 (5.4%)
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION	10/328 (3%)		10/336 (3%)
VIRAL INFECTION	1/328 (0.3%)		4/336 (1.2%)
GASTROENERITIS	4/328 (1.2%)		0/336 (0%)
NASOPHARYNGITIS	2/328 (0.6%)		5/336 (1.5%)
OTITIS MEDIA ACUTE	5/328 (1.5%)		3/336 (0.9%)
Respiratory, thoracic and mediastinal disorders
RHINORRHOEA	12/328 (3.7%)		16/336 (4.8%)
COUGH	21/328 (6.4%)		23/336 (6.8%)
OROPHARYNGEAL PAIN	7/328 (2.1%)		5/336 (1.5%)
RESPIRATORY DISORDER	4/328 (1.2%)		4/336 (1.2%)
NASAL CONGESTION	1/328 (0.3%)		4/336 (1.2%)
Skin and subcutaneous tissue disorders
DERMATITIS DIAPER	10/328 (3%)		12/336 (3.6%)
RASH	11/328 (3.4%)		12/336 (3.6%)

Limitations/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.