TY - JOUR
T1 - Effect of local prolonged-release incisional doxycycline on surgical site infection prophylaxis in abdominal colorectal surgery
T2 - the SHIELD 1 randomized clinical trial
AU - SHIELD 1 Investigators
AU - Zmora, Oded
AU - Fleshner, Phillip
AU - Barie, Philip S.
AU - Segev, Lior
AU - Viola, George M.
AU - Senagore, Anthony J.
AU - Spinelli, Antonino
AU - Belotserkovsky, Olga
AU - Sharoni, Shmuel
AU - Emanuel, Noam
N1 - Publisher Copyright:
Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
PY - 2024/10/1
Y1 - 2024/10/1
N2 - 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 greater than 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 greater than 20 cm subpopulation: 8% (D-PLEX) versus 17.5% (SOC) [RDE, -9.4%; 95% CI (-15.5%, -3.2%), P =0.0032]. In the greater than 10 to less than or equal 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.
AB - 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 greater than 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 greater than 20 cm subpopulation: 8% (D-PLEX) versus 17.5% (SOC) [RDE, -9.4%; 95% CI (-15.5%, -3.2%), P =0.0032]. In the greater than 10 to less than or equal 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.
UR - http://www.scopus.com/inward/record.url?scp=85213597062&partnerID=8YFLogxK
U2 - 10.1097/JS9.0000000000001824
DO - 10.1097/JS9.0000000000001824
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C2 - 38869970
AN - SCOPUS:85213597062
SN - 1743-9191
VL - 110
SP - 6658
EP - 6666
JO - International Journal of Surgery
JF - International Journal of Surgery
IS - 10
ER -