Title: Prospective, randomized, double-blind, Phase 2 dose-ranging study comparing efficacy and safety of imipenem/cilastatin plus relebactam with imipenem/cilastatin alone in patients with complicated urinary tract infections
Sims, M et al.
What You Need to Know:
Results of a phase 2 study found that addition of relebactam, a β-lactamase inhibitor used to restore the activity of imipenem against imipenem non-susceptible pathogens, was as effective as treatment with imipenem/cilastatin alone in patients with complicated urinary tract infections (cUTI) or acute pyelonephritis.
- Phase 2 study evaluated the safety, efficacy, and tolerability of relebactam in patients with cUTI or acute pyelonephritis
- Patients were randomized (1:1:1) to receive imipenem/cilastatin + 250mg relebactam, imipenem/cilastatin + 125mg relebactam, or imipenem/cilastatin alone; each was administered every 6 hours for 4-14 days
- Primary endpoint: “favourable microbiological response rate (pathogen eradication) at discontinuation of intravenous therapy (DCIV) in the microbiologically evaluable (ME) population”
- “Non-inferiority of imipenem/cilastatin+relebactam over imipenem/cilastatin alone was defined as lower bounds of the 95% CI for treatment differences being above –15%”
- ME population included 71 patients in the imipenem/cilastatin + 250mg relebactam group, 79 patients in the imipenem/cilastatin + 125mg relebactam group, and 80 patients in the imipenem/cilastatin group
- Microbiological response rates: 95.5% for imipenem/cilastatin + 250mg relebactam patients, 98.6% for imipenem/cilastatin + 125mg relebactam patients, and 98.7% for imipenem/cilastatin patients
- Non-inferiority over imipenem/cilastatin was confirmed for both doses of imipenem/cilastatin + relebactam
- Clinical response rates: 97.1%, 98.7%, and 98.8% for the imipenem/cilastatin + 250mg relebactam, imipenem/cilastatin + 125mg relebactam, and imipenem/cilastatin groups, respectively
- Microbiological responses at DCIV for patients with imipenem non-susceptible pathogens (n=23): 100% in each group
- Treatment-emergent adverse events: experienced by 28.3% of imipenem/cilastatin + 250mg relebactam patients, 29.3% of imipenem/cilastatin + 125mg relebactam patients, and 30.0% of imipenem/cilastatin patients
- Across groups, the most common treatment-related adverse events were diarrhea, nausea, and headache, which occurred in 1-4% of patients