Zmora Oded, Fleshner Phillip, Barie Philip S, Segev Lior, Viola George M, Senagore Anthony J, Spinelli Antonino, Belotserkovsky Olga, Sharoni Shmuel, Emanuel Noam
Department of Surgery, Shamir Medical Center, Be'er Ya'akov.
Division of Colorectal Surgery, Cedars-Sinai Medical Center, Los Angeles, CA.
Int J Surg. 2024 Oct 1;110(10):6658-6666. doi: 10.1097/JS9.0000000000001824.
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.
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.
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).
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.
尽管采取了先进的感染控制措施，包括术前抗生素预防，但手术部位感染（SSI）仍然是一个挑战。本研究旨在测试在伤口闭合前局部应用一种新型的长效强力霉素-聚合物-脂质包封基质（D-PLEX），并与标准治疗（SOC）同时使用，是否能降低择期腹部结直肠手术后切口SSI的发生率。
这是一项2020年6月至2022年6月间进行的3期随机、对照、双盲、多国研究（SHIELD 1）。至少有一个腹部切口长度大于10 cm的患者按1:1随机分为研究组（D-PLEX+SOC）或对照组（SOC）。主要结局是切口SSI、切口再次干预和全因死亡率的综合指标。
共分析了974例患者，其中579例（59.4%）为男性。平均年龄（±标准差）为64.2±13.0岁。主要结局在D-PLEX组患者中的发生率为9.3%，而SOC组为12.1%[风险差异估计值（RDE），-2.8%；95%置信区间（-6.7%，1.0%），P =0.1520]。在按切口长度进行的预先指定分析中，在切口长度大于20 cm的亚组中观察到主要结局有所降低：8%（D-PLEX）对17.5%（SOC）[RDE，-9.4%；95%置信区间（-15.5%，-3.2%），P =0.0032]。在切口长度大于10 cm至小于或等于20 cm的亚组中，未观察到降低：9.9%对7.9%[RDE，2.0%；95%置信区间（-2.8%，6.7%），P =0.4133]。对SSI风险增加（≥1种患者特异性合并症）患者的探索性事后分析表明，主要结局的发生率有所降低：9.0%（D-PLEX）对13.7%（SOC）[RDE，-4.8%；95%置信区间（-9.5%，-0.1%），P =0.0472]。D-PLEX的安全性良好（两组间治疗中出现的不良事件无差异）。
SHIELD 1研究未达到降低切口SSI、切口再次干预或全因死亡率的主要结局。预先指定和事后分析表明，D-PLEX可能降低包括长切口在内的SSI风险增加患者的主要结局事件发生率。
