Urinary Tract Infections | The SCOUT Study: Short Course Therapy for Urinary Tract Infections in Children
Urinary Tract Infections research study
What is the primary objective of this study?
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).
Who is eligible to participate?
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.
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Urinary Tract Infections
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:Trimethoprim sulfamethoxazole, cefixime, or cephalexinAfter five days of active drug, five additional days of one of the following: 1) Oral suspension 200 mg of sulfamethoxazole/40 mg trimethoprim per 5mL. 8 mg/kg/day Trimethoprim in 2 divided doses 2) Reconstituted oral suspension containing 100 mg of cefixime as a trihydrate per 5 mL for small children or 200 mg of cefixime as a trihydrate per 5 mL for large children 3) Reconstituted oral suspension 250mg anhydrous cephalexin per 5mL for small children and two packages of oral suspension of 250mg anhydrous cephalexin per 5mL for large children
Drug:PlaceboAfter five days of active drug, five days of placebo with the same flavoring as active counterpart. Dosage, dosage form, frequency and duration would be matched to each active counterpart.
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
Standard course (10 days of active antibiotic)Five days of continued antibiotic following five days of the antibiotic originally prescribed by the patient's treating clinician. Treatments include: 8 mg/kg/day of Trimethoprim in 2 divided doses (Max 160mg BID); 8 mg/kg/day cefixime in 1 dose (Max 400 mg); 50mg/kg/day cephalexin in 3 divided doses
Short course (5 days of active antibiotic, 5 days of placebo)Five days of placebo following five days of the antibiotic originally prescribed by the patient's treating clinician.
Start Date: May 2012
Completed Date: April 2018
Phase: Phase 2
Primary Outcome: Occurrence of treatment failures between short-course and standard-course therapies
Secondary Outcome: Occurrence of recurrent infections
Study sponsors, principal investigator, and references
Principal Investigator: Theoklis Zaoutis, MD, MSCE
Lead Sponsor: Children's Hospital of Philadelphia
Collaborator: University of Pittsburgh