Effect of local prolonged-release incisional doxycycline on surgical site infection prophylaxis in abdominal colorectal surgery: The SHIELD 1 randomized clinical trial.

Autor:	Zmora O; Department of Surgery, Shamir Medical Center, Be'er Ya'akov, Israel., Fleshner P; Division of Colorectal Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Barie PS; Department of Surgery, Weill Cornell Medicine, New York, NY, USA., Segev L; Department of General and Oncological Surgery-Surgery C, Sheba Medical Center, Tel Hashomer, Israel.; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel., Viola GM; Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Senagore AJ; Colorectal Surgeon. AJS Innovative Solutions LLC, Holland, Michigan, USA., Spinelli A; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele - Milan, Italy.; IRCCS Humanitas Research Hospital, Rozzano - Milan, Italy., Belotserkovsky O; PolyPid Ltd., Petach Tikvah, Israel., Sharoni S; PolyPid Ltd., Petach Tikvah, Israel., Emanuel N; PolyPid Ltd., Petach Tikvah, Israel.
Jazyk:	angličtina
Zdroj:	International journal of surgery (London, England) [Int J Surg] 2024 Jun 13. Date of Electronic Publication: 2024 Jun 13.
DOI:	10.1097/JS9.0000000000001824
Abstrakt:	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. Competing Interests: Conflict of Interest Disclosures: Barie was a consultant to the sponsoring company as part of a scientific advisory board held on the study results. Viola and Spinelli were members of the adjudication committee. Emanuel, Belotserkovsky, Senagore and Sharoni are paid employees or scientific advisors of the sponsoring company and own stock/stock options. No other disclosures have been reported. (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
Databáze:	MEDLINE
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