Abstract

Context: Urinary tract infections (UTIs) represent a 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 patients selection and the efficacy endpoints in febrile pediatric UTI CTs. Data Sources: Medline, Embase, Cochrane central databases and ClinicalTrials.gov between January 1, 1990, and November 24, 2016. Study Selection: We combined MeSH and free-text terms for: “urinary tract infections”, AND “therapeutics”, AND “clinical trials” in children (0–18 years), identifying 3,086 papers. Data Extraction: Two independent reviewers assessed study quality and performed data extraction. Results: Forty CTs investigating 4,381 cases of pediatric febrile UTIs were included. Positive urine culture and fever were the most common inclusion criteria (93% and 78%, respectively). Urine sampling method, pyuria and colonies thresholds were highly variable. Clinical and microbiological endpoints were assessed in 88% and 93% of the studies, respectively. Timing for endpoints 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 endpoints consistently with this guidance. Limitations: Mixed population of healthy children and with underlying condition. Six trials studied a subgroup of patients with afebrile UTI. Conclusions: We observed a wide variability in the microbiological inclusion criteria and the timing for endpoints 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 required.