A Randomized, Observer-Blinded, Active-Controlled, Phase IIIb Study to Compare IV/Oral Delafloxacin Fixed-Dose Monotherapy With Best Available Treatments in a Microbiologically Enriched Population With Surgical Site Infections: The DRESS Study

Abstract

Background: Surgical site infections (SSIs) are the most common skin and skin structure infections and are mostly polymicrobial, requiring hospitalization and broad-spectrum antibiotics. This clinical trial evaluated the noninferiority of delafloxacin vs best available therapy (BAT) for the treatment of superficial or deep incisional SSI following a cardiothoracic/related leg or abdominal surgical procedure.

Methods: In this randomized, observer-blinded, active-controlled, parallel-group, multicenter, phase IIIb study, patients with SSI were randomized 1:1 to receive delafloxacin 300 mg intravenous (IV)/450 mg oral (OS) or BAT IV/OS (vancomycin or linezolid for cardiothoracic SSI, piperacillin/tazobactam or tigecycline for abdominal SSI). The primary end point was clinical success, defined as the clinical response (cure or improved) at test of cure (TOC), performed 7-14 days after end of treatment (EOT) visit. Secondary end points were clinical success at EOT, sustained clinical response at last follow-up (LFU), microbiological response, and safety.

Results: Thi study enrolled 266 patients (delafloxacin = 134; BAT = 132) with comparable baseline characteristics between the 2 treatment arms. Delafloxacin clinical success was noninferior vs BAT at TOC visit (91.8% vs 90.2%, respectively). Similar efficacy was confirmed at LFU (91.8% delafloxacin; 87.9% BAT). Comparable microbiological response was obtained with delafloxacin (89.5%) and BAT (79.4%). Delafloxacin and BAT demonstrated comparable treatment adverse event rates (23.9% and 19.7%, respectively), mostly mild-to-moderate gastrointestinal reactions.

Conclusions: This study provided new data on delafloxacin in SSIs, covering the need for effective empiric treatment against the wide spectrum of pathogens involved in these infections.

Clinical trials registration: NCT04042077; 2018-001082-17 (EudraCT).

Keywords: acute bacterial skin and skin structure infections (ABSSSIs); clinical success; delafloxacin; safety; surgical site infections (SSIs).

Figure 1.

Visits and treatment schedule of the DRESS study. Abbreviations: BAT, best available therapy; DRESS, Delafloxacin intRavenous and oral monothErapy in Surgical Site infections; IRLOS, infection-related length of stay; SSI, surgical site infection.

Figure 2.

Clinical response at the TOC, EOT, and LFU time points in the ITT populations. At TOC visit: CRD = 0.0171 (95% CI, −0.0568 to 0.0910; P = .6661). Noninferiority: met. At EOT visit: CRD = 0.0001 (95% CI, −0.0660 to 0.0662; P = .6254). Noninferiority: met. At LFU visit: CRD = 0.0387 (95% CI, −0.0391 to 0.1165; P = .3126). Noninferiority: met. Confidence intervals were calculated using the Miettinen and Nurminen methods. If the LL of the 2-sided 95% CI was >−0.10, it was concluded that delafloxacin was noninferior to the reference treatment arm for treating patients with cardiothoracic or abdominal SSI. If the LL of the 2-sided 95% CI was >0, then delafloxacin was declared superior to the reference treatment arm for treating patients with cardiothoracic or abdominal SSI. The P value was calculated using the Mantel-Haenszel method. If the P value was lower than .05, then delafloxacin was declared superior to the reference treatment arm for treating patients with cardiothoracic or abdominal SSI. Abbreviations: BAT, best available therapy; CRD, common risk denominator; EOT, end of treatment; ITT, intention-to-treat; LFU, last follow-up; SSI, surgical site infection; TOC, test of cure.

Figure 3.

Clinical response at the TOC, EOT, and LFU time points in the CE populations. At TOC visit: CRD = 0.0322 (95% CI, −0.0325 to 0.0969). Noninferiority: met. At EOT visit: CRD = 0.0424 (95% CI, −0.0193 to 0.1040). Noninferiority: met. At LFU visit: CRD = 0.0359 (95% CI, −0.0330 to 0.1049). Noninferiority: met. Confidence intervals were calculated using the Miettinen and Nurminen methods. If the LL of the 2-sided 95% CI was >−0.10, it was concluded that delafloxacin was noninferior to the reference treatment arm for treating patients with cardiothoracic or abdominal SSI. If the LL of the 2-sided 95% CI was >0, then delafloxacin was declared superior to the reference treatment arm for treating patients with cardiothoracic or abdominal SSI. Abbreviations: BAT, best available therapy; CE, clinically evaluable; CRD, common risk denominator; EOT, end of treatment; LFU, last follow-up; SSI, surgical site infection; TOC, test of cure.