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INTRODUCTION: Despite advanced infection control practices including preoperative antibiotic prophylaxis, surgical site infection (SSI) remains a challenge. This study aimed to test whether local administration of a novel prolonged-release Doxycycline-Polymer-Lipid Encapsulation matriX (D-PLEX) before wound closure, concomitantly with standard of care (SOC), reduces the incidence of incisional SSI after elective abdominal colorectal surgery. MATERIALS AND METHODS: This was a phase 3 randomized, controlled, double-blind, multinational study (SHIELD 1) between June 2020 to June 2022. Patients with at least one abdominal incision length >10 cm were randomized 1:1 to the investigational arm (D-PLEX+SOC) or control (SOC) arm . The primary outcome was a composite of incisional SSI, incisional reintervention, and all-cause mortality. RESULTS: A total of 974 patients were analyzed, of whom 579 (59.4%) were male. The mean age (±SD) was 64.2±13.0 years. The primary outcome occurred in 9.3% of D-PLEX patients versus 12.1% (SOC) (risk difference estimate [RDE], -2.8%; 95% CI [-6.7%, 1.0%], P=0.1520). In a pre-specified analysis by incision length, a reduction in the primary outcome was observed in the >20 cm subpopulation: 8% (D-PLEX) versus 17.5% (SOC) (RDE, -9.4%; 95% CI [-15.5%, -3.2%], P=0.0032). In the >10 to ≤20 cm subgroup, no reduction was observed: 9.9% versus 7.9% (RDE, 2.0%; 95% CI [-2.8%, 6.7%], P=0.4133). Exploratory post-hoc analyses of patients with increased SSI risk (≥1 patient-specific comorbidity) indicated a reduction in the incidence of the primary outcome: 9.0% (D-PLEX) versus 13.7% (SOC) (RDE, -4.8%; 95% CI [-9.5%, -0.1%], P=0.0472). The D-PLEX safety profile was good (no difference in treatment-emergent adverse events between the groups). CONCLUSIONS: The SHIELD-1 study did not meet its primary outcome of reduced incisional SSI, incisional reinterventions, or all-cause mortality. Pre-specified and post-hoc analyses suggested that D-PLEX may reduce the incidence of the primary outcome event in patients with increased SSI risk, including lengthy incisions.

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BACKGROUND: D-PLEX100 is a novel drug-eluting lipid polymer matrix that supplies a high, local concentration of doxycycline for approximately 30 days. The objective of this post-hoc analysis was to assess the efficacy of D-PLEX100 in preventing superficial and deep SSIs in patients with ≥2 risk factors. PATIENTS AND METHODS: A post-hoc analysis of a previously reported prospective randomized trial assessing D-PLEX100 plus Standard of Care (SOC) versus SOC alone in colorectal surgery was performed to assess SSI rate in patients with ≥2 risk factors. RESULTS: The overall incidence of SSI was significantly lower for the D-PLEX100 arm (9.9%) versus SOC (21%), p = 0.033. Patients with ≥2 risk factors, SSI incidence was 37.5% for SOC and 15.8% in D-PLEX100 treated patients. CONCLUSIONS: D-PLEX100 reduces the incidence of SSIs beyond benefits associated with SOC treatment alone and including patients with ≥2 risk factors. D-PLEX100 may be a promising addition to established SSI prophylaxis bundles.

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INTRODUCTION: Sternal wound infection (SWI) is a devastating postcardiac surgical complication. D-PLEX100 (D-PLEX) is a localized prolonged release compound applied as a prophylactic at the completion of surgery to prevent SWI. The D-PLEX technology platform is built as a matrix of alternating layers of polymers and lipids, entrapping an antibiotic (doxycycline). The objective of this study was to assess the safety profile and pharmacokinetics of D-PLEX in reducing SWI rates postcardiac surgery. METHOD: Eighty-one patients were enrolled in a prospective single-blind randomized controlled multicenter study. Sixty patients were treated with both D-PLEX and standard of care (SOC) and 21 with SOC alone. Both groups were followed 6 months for safety endpoints. SWI was assessed at 90 days. RESULTS: No SWI-related serious adverse events (SAEs) occurred in either group. The mean plasma Cmax in patients treated with D-PLEX was about 10 times lower than the value detected following the oral administration of doxycycline hyclate with an equivalent overall dose, and followed by a very low plasma concentration over the next 30 days. There were no sternal infections in the D-PLEX group (0/60) while there was one patient with a sternal infection in the control group (1/21, 4.8%). CONCLUSION: D-PLEX was found to be safe for use in cardiac surgery patients. By providing localized prophylactic prolonged release of broad-spectrum antibiotics, D-PLEX has the potential to prevent SWI postcardiac surgery and long-term postoperative hospitalization, reducing high-treatment costs, morbidity, and mortality.

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