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

NCT01595529 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 09-0103
• Study Type: interventional
• Target: 717
• Locations: 1 country
• Sites: 1

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).

Conditions

Urinary Tract Infection

Keywords

antibiotic therapy; antimicrobial resistance; children; E.coli; K.pneumoniae; parent study; SCOUT Study; spectrum stool bacteria; stool culture; urinary tract infections

Outcome Measures

Primary Outcomes (2)

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

  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.

  Day 11 through Day 14

• Comparison of Efficacy Based on Symptomatic Urinary Tract Infection (UTI) Between Short-course and Standard-course of Antibiotics. Per-protocol Population.

  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.

  Day 11 through Day 14

Secondary Outcomes (10)

• 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

• 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

• 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

• 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

• Comparison of the Number of Subjects With Asymptomatic Bacteriuria Following Short-course Versus Standard-course of Antibiotics.

  Day 11 through Day 14

Study Arms (2)

Active treatment

EXPERIMENTAL

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; Drug: Cephalexin; Drug: Trimethoprim/Sulfamethoxazole

Placebo treatment

PLACEBO COMPARATOR

5 days of placebo treatment to match physician-initiated therapy

Other: Placebo

Interventions

Cefixime DRUG

Cefixime 8 mg/kg/day orally, in 1 dose, with a maximum of 400 mg. Subjects originally receiving Cefdinir will receive Cefixime.

Active treatment

Cephalexin DRUG

Cephalexin 50mg/kg/day in 3 divided doses

Active treatment

Placebo OTHER

Placebo to match the other four active treatments

Placebo treatment

Trimethoprim/Sulfamethoxazole DRUG

8 mg/kg/day of Trimethoprim-sulfamethoxazole (TMP-SMX) orally in 2 divided doses, with a maximum dose of 160 mg twice a day.

Active treatment

Eligibility Criteria

• Age: 2 Months - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).
• Confirmed UTI (Urinary Tract Infection) diagnosis.
• Documented Clinical Improvement at Randomization.
• Afebrile: No documented temperature \> / = 100.4 degrees Fahrenheit or 38 degrees Celsius (measured anywhere on the body) 24 hours prior to the enrollment visit
• 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
• Only children who have been prescribed one of the four antibiotics for which a placebo is available will be eligible to participate.

You may not qualify if:

• 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.
• 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 (Vesicoureteral reflux), 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Children's Hospital of Pittsburgh of UPMC - General Academic Pediatric

Pittsburgh, Pennsylvania, 15213-3205, United States

Location

Related Publications (1)

• Zaoutis T, Shaikh N, Fisher BT, Coffin SE, Bhatnagar S, Downes KJ, Gerber JS, Shope TR, Martin JM, Muniz GB, Green M, Nagg JP, Myers SR, Mistry RD, O'Connor S, Faig W, Black S, Rowley E, Liston K, Hoberman A. Short-Course Therapy for Urinary Tract Infections in Children: The SCOUT Randomized Clinical Trial. JAMA Pediatr. 2023 Aug 1;177(8):782-789. doi: 10.1001/jamapediatrics.2023.1979.

  PMID: 37358858 DERIVED

MeSH Terms

Conditions

Urinary Tract Infections; Escherichia coli Infections

Interventions

Cefixime; Cephalexin; Trimethoprim, Sulfamethoxazole Drug Combination

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Elizabeth Rowley
• Organization: Westat

ElizabethRowley@westat.com

(919) 941-8325

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2012
• First Posted: May 10, 2012
• Study Start: May 18, 2012
• Primary Completion: June 30, 2019
• Study Completion: August 12, 2019
• Last Updated: August 6, 2020
• Results First Posted: July 13, 2020

Record last verified: 2013-10-22

Locations

US (1)