A Multicenter, Randomized, Double-Blind, Imipenem/Cilastatin-Controlled Clinical Study of Cefiderocol for the Treatment of Complicated Urinary Tract Infections Caused by Gram-Negative Pathogens in Chinese Adults

BACKGROUND: Cefiderocol, a siderophore cephalosporin, is approved for the treatment of complicated urinary tract infections (cUTIs) and other indications in the USA, Europe, and Japan. However, clinical data from China are lacking. METHODS: This multicenter, randomized, double-blind, active-controlled bridging study was conducted in China closely mirroring the global APEKS-cUTI study. Adult patients (aged ≥18 years) with cUTI (with or without pyelonephritis) and ≥2 clinical symptoms were randomized 2:1 to receive either cefiderocol (2 g) or imipenem-cilastatin sodium (IPM/CS; 1 g) every 8 hours for 5-14 days. The primary endpoint was the composite response rate at the test-of-cure (TOC) visit within the microbiological intention-to-treat (micro-ITT) population. The point estimate of the difference >-15% in the primary endpoint between the two groups demonstrates the consistency with the efficacy results of the APEKS-cUTI study. RESULTS: Of 150 patients (cefiderocol, 100; IPM/CS, 50), 67 and 34 patients were in the micro-ITT population, respectively. At TOC, 62.7% (42/67) and 26.5% (9/34) of patients in the cefiderocol and IPM/CS groups achieved the composite response, respectively, (difference: 35.93% [95% CI, 17.92%-53.93%]). Treatment-emergent adverse events (TEAEs) occurred in 74.0% (74/100) and 80.0% (40/50) in the cefiderocol and IPM/CS groups, with drug-related TEAEs occurring in 27.0% (27/100) and 40.0% (20/50) of patients, respectively. TEAEs were mostly mild. However, four patients in the cefiderocol group discontinued due to TEAEs. CONCLUSION: Cefiderocol demonstrated efficacy, which was non-inferior to imipenem, and safety in Chinese adult cUTI patients supporting its approval in China, consistent with findings from the APEKS-cUTI study. TRIAL NUMBER: ChiCTR2400090538.