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.