C1. Clinical trials (abstracts submitted to C1 should choose a secondary category that describes the subject matter of the trial)
Late Breaking Abstract Submission
Background: Cefiderocol (CFDC) is a novel siderophore cephalosporin with activity against a broad range of Gram-negative bacteria. In this study, Day 14 all-cause mortality (ACM) rates were compared between CFDC and meropenem (MEM) in patients with nosocomial Gram-negative pneumonia.
Methods: The study (NCT03032380) was a Phase 3, international, double-blind, randomized, non-inferiority study in hospitalized patients with ventilator-associated, hospital-acquired, or healthcare-associated pneumonia caused by suspected Gram-negative bacteria. Patients were treated with CFDC (2 g, q8h) or MEM (2 g, q8h), both infused for 3 hours, for 7–14 days. Adjunctive linezolid (600 mg, q12h, ≥5 days) was given in both arms to cover Gram-positive bacteria. The primary endpoint was non-inferiority of CFDC to MEM for Day 14 ACM rate in the modified intent-to-treat population (mITT; non-inferiority margin: –12.5%). Key secondary endpoints were clinical and microbiological outcomes at test of cure (TOC), and Day 28 mortality. Safety was investigated up to 28 days after the end of treatment.
Results: In the ITT population, 148 pts were randomized to CFDC and 150 to MEM: 59.7% were ventilated, 32.6% had failure of prior therapy, the median APACHE II score was 15, and 6.0% had concomitant Gram-negative bacteremia at baseline. In the mITT population, non-inferiority of CFDC to MEM for Day 14 ACM was demonstrated; CFDC: 12.4% (18 out of 145 pts) vs MEM: 11.6% (17 out of 146 pts); treatment difference: 0.8; 95% confidence interval: –6.6; 8.2. Comparable Day 28 ACM (CFDC: 21.0% vs MEM: 20.5%), clinical cure (CFDC: 64.8% vs MEM: 66.7%), and microbiological eradication (CFDC: 47.6% vs MEM: 48.0%) rates were demonstrated in the mITT population at TOC. Clinical cure rates for major target pathogens at TOC were similar between CFDC and MEM arms (Figure). The rates of treatment-emergent adverse events (TEAEs), drug-related TEAEs, serious AEs, discontinuation due to TEAEs, and deaths were similar between treatment arms (Table).
Conclusion: This study demonstrated the non-inferiority of CFDC to high-dose MEM for the pre-specified endpoint of Day 14 ACM. No unexpected safety signals were observed in the study.