每日一次基于菠萝蛋白酶的酶促清创术治疗下肢静脉溃疡与凝胶载体（安慰剂）及非手术标准护理的对照研究：一项三臂多中心、双盲、随机对照试验。
Once daily Bromelain-based enzymatic debridement of venous leg ulcers versus gel vehicle (placebo) and non-surgical standard of care: a three-arm multicenter, double blinded, randomized controlled study.
作者信息
Shoham Yaron, Snyder Robert J, Katz Levy Yael, David Zarbiv Keren, Klinger Ety, Kramer Miri, Dove Cyaandi R, Avrahami Ram, Reyzelman Alex, Sigal Felix, Tovmassian Gregory, Shapira Eyal, Harats Moti, Perez-Clavijo Francisco, Lantis John C, Cazzell Shawn M, Dhillon Yadwinder S, Cuffy Cherison A, Egozi Dana, Vayser Dean, Singer Adam J, Galperin Richard C, Hanft Jason R, Martinez Cindy, Shalom Avshalom, Toutous-Trellu Laurence, Rosenberg Lior
机构信息
Department of Plastic and Reconstructive Surgery, Soroka University Medical Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheba, Israel.
MediWound Ltd., Yavne, Israel.
出版信息
EClinicalMedicine. 2024 Jul 27;75:102750. doi: 10.1016/j.eclinm.2024.102750. eCollection 2024 Sep.
BACKGROUND
Debridement is considered the first step in treatment of chronic wounds, however, current enzymatic and autolytic debridement agents are slow or ineffective. Previous studies have shown positive initial results with EscharEx® (EX-02 formulation), a Bromelain-based enzymatic debridement agent in development for chronic wounds. The main objective of this study was to assess its efficacy in debriding venous leg ulcers (VLU), compared to gel vehicle (GV) as a placebo control and to non-surgical standard of care (NSSOC).
METHODS
A prospective, randomized, multicenter, placebo-controlled trial in patients with VLU from 20 medical centers and clinics in the United States, Switzerland and Israel was undertaken. Patients were treated with daily topical applications of either EX-02, GV, or NSSOC (in a 3:3:2 ratio), until reaching complete debridement or up to 8 daily treatments (within 2 weeks), and then followed-up for up to 14 weeks. The primary efficacy endpoint was the incidence of complete debridement. This study is registered with ClinicalTrials.gov (NCT03588130) and EudraCT (number 2020-004861-38).
FINDINGS
A total of 196 patients were enrolled, and 119 randomized (between November 12th, 2019, and February 15th, 2022); 46 to the EX-02 arm, 43 to the GV arm, and 30 to the NSSOC arm. Eight patients dropped out of the study (2 in EX-02, 2 in GV, 4 in NSSOC). The incidence of complete debridement within 8 daily treatments was 63% (29/46 patients) in the EX-02 arm as compared to 30.2% (13/43 patients) in the GV arm (p = 0.004) and 13.3% (4/30 patients) in the NSSOC arm (p < 0.001). Sixty-five patients reported wound related adverse events throughout the study; 24 (52.2%), 27 (62.8%) and 14 (46.7%) patients in the EX-02, GV and NSSOC arms (p = NS). No deaths occurred during the study.
INTERPRETATION
EX-02 lead to a significantly higher incidence of complete debridement as compared to GV and NSSOC, without significant safety issues. Additional studies are needed to explore the benefits of EX-02 in VLU and other chronic wound etiologies.
FUNDING
MediWound Ltd.
背景
清创术被认为是慢性伤口治疗的第一步，然而，目前的酶解清创剂和自溶性清创剂作用缓慢或效果不佳。先前的研究表明，EscharEx®（EX - 02配方）作为一种正在开发用于治疗慢性伤口的菠萝蛋白酶基酶解清创剂，初步结果呈阳性。本研究的主要目的是评估其在清创下肢静脉溃疡（VLU）方面的疗效，与作为安慰剂对照的凝胶载体（GV）以及非手术标准护理（NSSOC）进行比较。
方法
在美国、瑞士和以色列的20个医疗中心和诊所对患有VLU的患者进行了一项前瞻性、随机、多中心、安慰剂对照试验。患者每日局部应用EX - 02、GV或NSSOC（比例为3:3:2）进行治疗，直至完全清创或最多进行8次每日治疗（在2周内），然后随访长达14周。主要疗效终点是完全清创的发生率。本研究已在ClinicalTrials.gov（NCT03588130）和EudraCT（编号2020 - 004861 - 38）注册。
研究结果
共纳入196例患者，119例被随机分组（在2019年11月12日至2022年2月15日期间）；46例进入EX - 02组，43例进入GV组，30例进入NSSOC组。8例患者退出研究（EX - 02组2例，GV组2例，NSSOC组4例）。在每日8次治疗内，EX - 02组完全清创的发生率为63%（29/46例患者），而GV组为30.2%（13/43例患者）（p = 0.004），NSSOC组为13.3%（4/30例患者）（p < 0.001）。在整个研究过程中，65例患者报告了与伤口相关的不良事件；EX - 02组、GV组和NSSOC组分别有24例（52.2%）、
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