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

Condition(s) targeted: Urinary Tract Infections

Intervention: Trimethoprim sulfamethoxazole, cefixime, or cephalexin (Drug); Placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Children's Hospital of Philadelphia

Official(s) and/or principal investigator(s):
Theoklis Zaoutis, MD, MSCE, Principal Investigator, Affiliation: Children's Hospital of Philadelphia

Overall contact:
Theoklis Zaoutis, MD, MSCE, Phone: 267-426-5570, Email: zaoutis@email.chop.edu

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, defined as symptomatic Urinary Tract Infection (UTI) through Test of Cure (TOC) on Day 11-14, as subjects who continue to take antibiotics for an additional 5 days (standard course therapy). 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).

Official title: Targeted Clinical Trials to Reduce the Risk of Antimicrobial Resistance The SCOUT Study: "Short Course Therapy for Urinary Tract Infections in Children"

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Occurrence of treatment failures between short-course and standard-course therapies

Secondary outcome:

Occurrence of recurrent infections

Occurrence of colonization with antimicrobial resistant bacteria

Occurrence of asymptomatic bacteriuria

Occurrence of clinical symptoms

Occurrence of positive urine cultures

Detailed description: The standard-of-care to treat uncomplicated UTIs is a 10-day course of antibiotics. Some studies in adults have shown that shorter courses of antibiotics are effective in treating urinary tract infections. The SCOUT Study will determine if five days of antibiotics works as well as 10 days of treatment in children. In addition, the SCOUT study will determine if the shorter 5-day course of antibiotics is less likely to contribute to antibiotic resistance. The study will try to find out if reducing the antibiotic course to five days of therapy can reduce the chance that antimicrobial resistant bacteria will develop in the gastrointestinal tract. Antibiotics kill the sensitive bacteria but stronger germs may be left to grow and multiply. Antimicrobial resistant bacteria are the bacteria that survive after taking an antibiotic. If these stronger germs grow, the antibiotics may not be as good at killing them. The study will compare children with urinary tract infections treated with 5 days of antibiotics + five days of placebo (no active medication) versus those treated with 10 full days of antibiotic therapy.

Minimum age: 2 Months. Maximum age: 10 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Age at randomization: at least two months (at least 36 weeks gestational age for

subjects < two years of age) to 10 years of age (120 months)

- Confirmed UTI diagnosis:

I. At least one of the symptoms consistent with the diagnosis of UTI including:

- 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

- Children > 2 years of age: suprapubic, abdominal, or flank pain or tenderness, or

urinary urgency, frequency, or hesitancy

- Children ≥ 2 months to 2 years of age: poor feeding or vomiting

AND II. Pyuria on urinalysis

- >=10 WBC/mm3 (uncentrifuged specimen) OR

- >=5 WBC/hpf (centrifuged specimen), OR

- Leukocyte esterase > trace on dipstick. AND

III. Culture proven infection with a single uropathogen:

- >=5 x 10^4 CFU/mL (catheterized or suprapubic aspiration urine specimen) OR

- >=10^5 CFU/mL (clean void specimen).

- Documented Clinical Improvement at Randomization

- Afebrile : No documented temperature equal or greater than 100. 4 °F or 38°C

(measured anywhere on the body) 24 hours prior to the enrollment visit AND

- Asymptomatic: report NONE of the following symptoms:

- 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

- 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).

- Parental/guardian permission (informed consent) and if appropriate, child assent

(if > seven years of age). Exclusion Criteria:

- A urine culture proven infection with more than one uropathogen of at least 50,000

CFU/mL collected via catheter or suprapubic aspiration OR at least 100,000 CFU/mL collected via clean void.

- A child hospitalized with a UTI that has the following: concomitant bacteremia

associated with the UTI, urosepsis, or is in intensive care.

- A child whose urine culture reveals an organism that is resistant to the initially

prescribed antibiotic.

- A child with a catheter-associated UTI.

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

- A child with phenylketonuria (PKU)

- A child diagnosed with congenital anomalies of the genitourinary tract

- UTI in children with known anatomic abnormalities of the genitourinary tract other

than VUR, duplicated collection systems, and hydronephrosis.

- A child that is not able to take oral medications

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

- Presence of an immunocompromising condition (e. g., HIV, malignancy, solid-organ

transplant recipients, use of chronic corticosteroids or other immunosuppressive agents).

- Unlikely to complete follow-up (e. g. not available for the two follow-up study visits

and the follow-up phone call)

- A child with a known history of type I hypersensitivity of the study antibiotics to

be prescribed

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

- Previous enrollment of individuals in this study.

- Planned enrollment during this study coincides with enrollment in another therapeutic

drug study (excluding vaccine).

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

- A child with Grade III-V VUR

- A child taking antibiotic prophylaxis for any reason.

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

Theoklis Zaoutis, MD, MSCE, Phone: 267-426-5570, Email: zaoutis@email.chop.edu

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States; Recruiting
Theoklis Zaoutis, MD, MSCE, Principal Investigator

Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15224, United States; Recruiting
Alejandro Hoberman, MD, Phone: 412-999-3277, Email: hoberman@chp.edu
Diana Kearney, CCRC, Phone: 412-692-6717, Email: diana.kearney@chp.edu
Alejandro Hoberman, MD, Principal Investigator

Starting date: May 2012
Last updated: June 23, 2015