Ertapenem versus piperacillin/tazobactam for diabetic foot infections in China: A Phase 3, multicentre, randomized, double-blind, active-controlled, non-inferiority trial

Abstract

Objectives: Few randomized controlled studies have compared antibiotic regimens against diabetic foot infections (DFIs) in Chinese patients. We evaluated the efficacy and safety of ertapenem versus piperacillin/tazobactam for the treatment of DFIs in Chinese patients. Methods: Patients with moderate to severe DFIs requiring parenteral antibiotics were randomized in a 1:1 ratio to receive ertapenem(1.0 g once daily) or piperacillin/tazobactam(4.5 g every 8 h) by 30 min intravenous (iv) infusions for ≥5 days. The primary outcome was favourable clinical response at discontinuation of iv therapy (DCIV). An evaluable-patient population was identified for primary analysis of non-inferiority at 215%. Safety was assessed. ClinicalTrials.gov: NCT01370616. Results: Of 565 patients randomized, 443 patients (ertapenem=219 and piperacillin/tazobactam=224) were clinically evaluable for primary analysis. In the clinically evaluable population, the proportions of patientswith favourable clinical response at DCIV were 93.6%(205/219) and 97.3%(218/224) in the ertapenemand piperacillin/tazobactam groups, respectively (difference: 23.8%, 95% CI: 28.3%, 0.0%). Ertapenem had a significantly lower favourable clinical response rate (91.5% versus 97.2%, 95% CI for difference: 212.1%, 20.3%) at DCIV in severe DFI patients. In the modified ITT population, 88.8% (237/267) and 90.6% (241/266) of patients in the ertapenem and piperacillin/ tazobactam groups, respectively, had favourable clinical responses at DCIV (difference: 21.9%, 95% CI: 27.3%, 3.3%). Microbiological eradications of causative pathogens and adverse events were similar between treatment groups. Conclusions: Treatment with ertapenem was non-inferior to piperacillin/tazobactam in Chinese patients with DFIs. Ertapenem treatment resulted in a markedly lower rate of clinical resolution in severe DFIs.