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)

Tracking Information

• First Submitted Date: May 8, 2012
• First Posted Date: May 10, 2012
• Results First Submitted Date: June 25, 2020
• Results First Posted Date: July 13, 2020
• Last Update Posted Date: August 6, 2020
• Actual Study Start Date: May 18, 2012
• Actual Primary Completion Date: June 30, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 25, 2020)

• Comparison of Efficacy Based on Symptomatic Urinary Tract Infection (UTI) Between Short-course and Standard-course of Antibiotics. [ Time Frame: 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:

  1. 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
  2. Pyuria on urinalysis AND
  3. 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.
• Comparison of Efficacy Based on Symptomatic Urinary Tract Infection (UTI) Between Short-course and Standard-course of Antibiotics. Per-protocol Population. [ Time Frame: 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:

  1. 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
  2. Pyuria on urinalysis AND
  3. 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.

Original Primary Outcome Measures (submitted: May 8, 2012)

Occurrence of treatment failures between short-course and standard-course therapies [ Time Frame: 12-14 days following initation of therapy ]

Comparison of efficacy, based on symptomatic UTI as assessed up to or at the TOC visit (Day 12-14), between short-course and standard-course therapies.

Current Secondary Outcome Measures (submitted: June 25, 2020)

• 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 ]
• 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 ]
• 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. [ Time Frame: Day 11 through Day 30 ]
  A child would have emergent antibiotic resistance if they:

  1. Had no antibiotic-resistant E.coli or K.pneumoniae at enrollment but one or both are now present. OR
  2. Had either antibiotic-resistant E.coli or K.pneumoniae at enrollment but now the other antibiotic-resistant organism is present OR
  3. Had antibiotic-resistant E.coli and/or K.pneumoniae at enrollment, but have now developed resistance to new antibiotics in either organism.
• 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. [ Time Frame: Day 11 through Day 30 ]
  A child would have emergent antibiotic resistance if they:

  1. Had no antibiotic-resistant E.coli or K.pneumoniae at enrollment but one or both are now present. OR
  2. Had either antibiotic-resistant E.coli or K.pneumoniae at enrollment but now the other antibiotic-resistant organism is present OR
  3. Had antibiotic-resistant E.coli and/or K.pneumoniae at enrollment, but have now developed resistance to new antibiotics in either organism.
• Comparison of the Number of Subjects With Asymptomatic Bacteriuria Following Short-course Versus Standard-course of Antibiotics. [ Time Frame: Day 11 through Day 14 ]
  Asymptomatic Bacteriuria is defined in any SCOUT subject by:

  1. 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
  2. A positive urine culture
     • 5 x 104 CFU/mL (catheterized or suprapubic aspiration urine specimen) OR
     • >105 CFU/mL (clean void specimen).
• Comparison of the Number of Subjects With Asymptomatic Bacteriuria Following Short-course Versus Standard-course of Antibiotics. Per-protocol Population. [ Time Frame: Day 11 through Day 14 ]
  Asymptomatic Bacteriuria is defined in any SCOUT subject by:

  1. 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
  2. A positive urine culture
     • 5 x 104 CFU/mL (catheterized or suprapubic aspiration urine specimen) OR
     • >105 CFU/mL (clean void specimen).
• 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 ]
• 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 ]
• Comparison of the Number of Subjects With Positive Urine Cultures Following Short-course Versus Standard-course of Antibiotics. [ Time Frame: Up to Day 14 ]
• 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 ]

Original Secondary Outcome Measures (submitted: May 8, 2012)

• Occurrence of recurrent infections [ Time Frame: 12-14 days following initation of therapy ]
  Comparison of number of subjects that have a recurrent infection (includes a relapse UTI or a reinfection) at any time after the TOC visit (Day 12-14), following short-course versus standard-course (of antibiotics.
• Occurrence of colonization with antimicrobial resistant bacteria [ Time Frame: 24-26 days following initiation of therapy ]
  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 as assessed through Day 24-26, following short-course versus standard course of antibiotics.
• Occurrence of asymptomatic bacteriuria [ Time Frame: 12-14 days following initiation of therapy ]
  Comparison of the number of subjects with asymptomatic bacteriuria in subjects treated with short-course therapy as compared to the number of subjects treated with standard course therapy at the TOC visit
• Occurrence of clinical symptoms [ Time Frame: 12-14 days following initiation of therapy ]
  Comparison of the number of subjects with clinical symptoms that may be related to a UTI in subjects treated with short-course therapy as compared to the number of subjects treated with standard course therapy prior to or at the TOC visit.
• Occurrence of positive urine cultures [ Time Frame: 12-14 days following initiation of therapy ]
  Comparison of the number of subjects with positive urine culture prior to or at TOC between subjects treated with short-course therapy and those treated with standard course therapy.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The SCOUT Study: "Short Course Therapy for Urinary Tract Infections in Children"
• Official Title: Targeted Clinical Trials to Reduce the Risk of Antimicrobial Resistance The SCOUT Study: "Short Course Therapy for Urinary Tract Infections in Children"
• 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).
• 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Urinary Tract Infection

Intervention

• 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
• Other: Placebo
  Placebo to match the other four active treatments
• 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.

Study Arms

• 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)
  Interventions:

  • Drug: Cefixime
  • Drug: Cephalexin
  • Drug: Trimethoprim/Sulfamethoxazole
• Placebo Comparator: Placebo treatment
  5 days of placebo treatment to match physician-initiated therapy
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 8, 2019): 717
• Original Estimated Enrollment (submitted: May 8, 2012): 746
• Actual Study Completion Date: August 12, 2019
• Actual Primary Completion Date: June 30, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

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

   2. 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

4. 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)
5. 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Months to 10 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01595529
• Other Study ID Numbers: 09-0103
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• Original Responsible Party: Theoklis Zaoutis, Children's Hospital of Philadelphia, Associate Chief, Division of Infectious Diseases
• Current Study Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Original Study Sponsor: Children's Hospital of Philadelphia
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: National Institute of Allergy and Infectious Diseases (NIAID)
• Verification Date: October 22, 2013