The SCOUT Study: "Short Course Therapy for Urinary Tract Infections in Children"
Condition: Urinary Tract Infection
MeSH terms: Infections; Communicable Diseases; Urinary Tract Infections
Intervention: Cefixime; Cephalexin; Placebo; Trimethoprim/Sulfamethoxazole
Intervention description: Cefixime 8 mg/kg/day orally, in 1 dose, with a maximum of 400 mg. Subjects originally receiving Cefdinir will receive Cefixime.; Cephalexin 50mg/kg/day in 3 divided doses; Placebo to match the other four active treatments; 8 mg/kg/day of Trimethoprim-sulfamethoxazole (TMP-SMX) orally in 2 divided doses, with a maximum dose of 160 mg twice a day.
Intervention MeSH terms: Trimethoprim; Sulfamethoxazole; Cephalexin; Cefixime
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 717.0
Sex: All
Minimum age: 2 Months
Maximum age: 10 Years
Healthy volunteers: No
Keywords: antibiotic therapy; antimicrobial resistance; children; E.coli; K.pneumoniae; parent study; SCOUT Study; spectrum stool bacteria; stool culture; urinary tract infections

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).
    

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.