RCT 非劣勢 Phase 2/3
6 g ZTI-01 (IV fosfomycin) intravenously administered every 8 hours (18g total daily dose for 7-14 calendar days)
4.5 g piperacillin/tazobactam (4 g piperacillin/0.5 g tazobactam) intravenously administered every 8 hours (13.5g total daily dose for 7-14 calendar days)
Primary Outcome Measures
Number of Patients With an Overall Success [ Time Frame: TOC Visit (Day 19) ]
Clinical cure (resolution or significant improvement in signs and symptoms) and microbiologic eradication (baseline pathogen) in m-MITT population
Safety and Efficacy of ZTI-01 (IV Fosfomycin) vs Piperacillin/Tazobactam for Treatment cUTI/AP Infections - Full Text View - ClinicalTrials.gov
ZTI-01 (fosfomycin for injection) is an epoxide antibiotic with a differentiated mechanism of action (MOA) inhibiting an early step in bacterial cell wall synthesis. ZTI-01 has broad in vitro spectrum of activity, including multidrug-resistant Gram-negative pathogens, and is being developed for treatment of complicated urinary tract infection (cUTI) and acute pyelonephritis (AP) in the United States.
Hospitalized adults with suspected or microbiologically confirmed cUTI/AP were randomized 1:1 to 6 g ZTI-01 q8h or 4.5 g IV piperacillin-tazobactam (PIP-TAZ) q8h for a fixed 7-day course (no oral switch); patients with concomitant bacteremia could receive up to 14 days.
Of 465 randomized patients, 233 and 231 were treated with ZTI-01 and PIP-TAZ, respectively. In the microbiologic Modified Intent-to-Treat (m-MITT) population, ZTI-01 met the primary objective of noninferiority compared with PIP-TAZ with overall success rates of 64.7% (119/184 patients) vs 54.5% (97/178 patients), respectively; treatment difference was 10.2% (95% CI: 0.4, 20.8). Clinical cure rates at test-of-cure (TOC, Day 19-21) were high and similar between treatments (90.8% [167/184] vs 91.6% [163/178], respectively). In post-hoc analysis using unique pathogens typed by pulsed-field gel electrophoresis, overall success rates at TOC in mMITT were 69.0% (127/184) for ZTI-01 vs 57.3% (102/178) for PIP-TAZ (difference 11.7% 95% CI: 1.3, 22.1). ZTI-01 was well tolerated. Most TEAEs, including hypokalemia and elevated serum aminotransferases, were mild and transient.
ZTI-01 was effective for treatment of cUTI including AP, and offers a new IV therapeutic option with a differentiated MOA for patients with serious Gramnegative infections.
Clinical Trial Registration