Urinary Tract Infection Antibiotic Trial Study Design: A Systematic Review.

CONTEXT: Urinary tract infections (UTIs) represent common bacterial infections in children. No guidance on the conduct of pediatric febrile UTI clinical trials (CTs) exist.

OBJECTIVE: To assess the criteria used for patient selection and the efficacy end points in febrile pediatric UTI CTs.

DATA SOURCES: Medline, Embase, Cochrane central databases, and clinicaltrials.gov were searched between January 1, 1990, and November 24, 2016.

STUDY SELECTION: We combined Medical Subject Headings terms and free-text terms for "urinary tract infections" and "therapeutics" and "clinical trials" in children (0-18 years), identifying 3086 articles.

DATA EXTRACTION: Two independent reviewers assessed study quality and performed data extraction.

RESULTS: We included 40 CTs in which a total of 4381 cases of pediatric UTIs were investigated. Positive urine culture results and fever were the most common inclusion criteria (93% and 78%, respectively). Urine sampling method, pyuria, and colony thresholds were highly variable. Clinical and microbiological end points were assessed in 88% and 93% of the studies, respectively. Timing for end point assessment was highly variable, and only 3 studies (17%) out of the 18 performed after the Food and Drug Administration 1998 guidance publication assessed primary and secondary end points consistently with this guidance.

LIMITATIONS: Our limitations included a mixed population of healthy children and children with an underlying condition. In 6 trials, researchers studied a subgroup of patients with afebrile UTI.

CONCLUSIONS: We observed a wide variability in the microbiological inclusion criteria and the timing for end point assessment. The available guidance for adults appear not to be used by pediatricians and do not seem applicable to the childhood UTI. A harmonized design for pediatric UTIs CT is necessary.