Evaluation of ASEPSIS Score as a Secondary Endpoint in the Phase 3 SHIELD II Trial of D-PLEX100 in Colorectal Surgery

Authors:
Robert Sawyer, Livnat Levy, Elena Zafirovikj

Body of Abstract:
Background: D-PLEX100 is a novel extended-release doxycycline delivery system applied as a single dose to the surgical site prior to incision closure. D-PLEX100 was evaluated in SHIELD II, a randomized, double-blind, controlled trial in patients undergoing abdominal colorectal surgery. The study met its primary endpoint, demonstrating a significantly lower rate of treatment failure (defined as occurrence of any of the following: surgical site infection (SSI) in the target incision, re-intervention, or death) in the D-PLEX100 arm compared with standard of care (SoC). ASEPSIS score was used as a post-operative wound surveillance tool to standardize the assessment and grading of surgical site infections based on observable clinical criteria. The score is determined based on the following characteristics: Additional treatment, Serous discharge, Erythema, Purulent exudate, Separation of deep tissue, Isolation of bacteria, Stay duration as inpatient. It provides an objective and standardized approach to wound assessment, offering a quantitative measure of SSI severity derived from specific, predefined clinical findings. Herein, we report on key secondary endpoints related to ASEPSIS scoring.

Methods: Abdominal colorectal surgery patients were randomized to receive D-PLEX100 plus SoC systemic antibiotics or SoC alone. The primary outcome was treatment failure defined as a composite of any one of the following: adjudicated incision SSI, re-intervention at the target incision site, and mortality. One of the three key secondary endpoints was determining ASEPSIS scores at each study visit as part of the surgical site assessment. Number of subjects with at least one ASEPSIS score of >20 within 30 days post abdominal (index) surgery were compared between both study arms in the intention-to-treat (ITT) population. The averages of cumulative ASEPSIS assessment scores were also reported for those who experienced adjudicated SSI within 30 days post index surgery.

Results: SHIELD II had 798 subjects [n = 405 (D-PLEX arm) n = 393 (SOC arm)] in the ITT population. There was a 38% relative risk reduction in the primary outcome in the D-PLEX100 arm compared to SoC [44 (10.9%) vs 71 (18.1%); difference -7.2 (95% CI, -12.1 to -2.3), p = 0.0039]. The proportion of subjects with at least one ASEPSIS score >20 was lower in the D-PLEX100 arm [8/391 (2.0%)] compared to the SoC arm [21/377 (5.6%)]. The stratified risk difference was -3.5 (95% CI -6.2 to ‑0.8; p = 0.0103). The median cumulative ASEPSIS score was 175 in the D-PLEX arm and 216.25 in the SoC arm. The median cumulative ASEPSIS score within the SSI period was 110 in the D-PLEX arm and 160 in the SoC arm.

Conclusions: The use of D-PLEX100 resulted in improved outcomes for abdominal colorectal surgery patients, specifically demonstrating reduction in treatment failures compared to SoC antibiotics. D-PLEX100 was also associated with lower rates of wound infections as determined by ASEPSIS scoring.