227. Impact of Asymptomatic Bacteriuria on Primary Efficacy Analyses in the Evaluation of Novel Antimicrobials for the Treatment of Patients with Urinary Tract Infection
Abstract
Per FDA Guidance, the primary efficacy endpoint for trials evaluating antimicrobials for treatment of uncomplicated urinary tract infection (uUTI) and complicated urinary tract infection (cUTI) is a combined clinical/microbiologic outcome response. Overall success requires both resolution of UTI symptoms and demonstration that the causative uropathogen is reduced to < 103 CFU/mL at a fixed time point after randomization, regardless of whether the patient is symptomatic. In clinical practice, it is not standard of care to routinely screen for or treat asymptomatic bacteriuria (ASB), nor to obtain ‘proof of cure’ cultures. In the clinical trial setting, the impact of post-treatment asymptomatic bladder recolonization on the rates of microbiologic response, re-infection, or emergence of resistance is unknown.
Study IT001-301 and -302 are double blind, double-dummy, Phase 3 randomized trials comparing sulopenem to comparator for patients with pyuria, bacteriuria, and clinical signs/symptoms of uUTI and cUTI, respectively. In Study 301, 1671 ambulatory female adults with uUTI were randomized to oral sulopenem bid x 5d or oral ciprofloxacin bid x 3d. In Study 302, 1395 hospitalized adults with cUTI were randomized to sulopenem IV once daily x 5d followed by oral sulopenem bid or ertapenem IV once daily x 5d followed by either oral ciprofloxacin or amoxicillin-clavulanate bid, depending on baseline uropathogen susceptibility. The primary endpoint was overall (clinical +…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 1,671 participants or records.
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