Abramowitz Steven D, Marko Xhorlina, D'Souza Donna, Noor Sonya, Pereira Keith, Silver Mitchell J, Rosenberg Stuart P, Markovitz Craig D, Tu Thomas, Weinberg Ido, Black Stephen
MedStar Health, Washington, DC.
Corewell Health, Dearborn, MI.
Am Heart J. 2025 Mar;281:92-102. doi: 10.1016/j.ahj.2024.10.016. Epub 2024 Nov 3.
Deep vein thrombosis (DVT) is a common medical condition that is associated with clinically significant sequelae, including postthrombotic syndrome (PTS). Anticoagulation alone remains the guideline-recommended treatment for many patients with iliofemoral DVT. Recent technological advances have led to an increase in the use of mechanical thrombectomy for DVT, but mechanical thrombectomy-based procedures have not yet been compared with standard-of-care anticoagulation therapy in randomized studies.
The DEFIANCE study (ClinicalTrials.gov: NCT05701917) is an international and actively enrolling randomized controlled trial (RCT) in lower extremity DVT assessing an interventional strategy that includes mechanical thrombectomy with the ClotTriever System (Inari Medical, Irvine, CA) versus anticoagulation alone. Approximately 300 patients with unilateral iliofemoral DVT and symptom duration ≤ 12 weeks will be randomized 1:1. Study conduct includes an independent core laboratory for duplex ultrasound assessment, an independent medical monitor for safety adjudication, and evaluation of PTS severity on the Villalta scale using best clinical practices. The primary endpoint is a composite outcome structured as a hierarchal win ratio of 1) the occurrence of treatment failure or therapy escalation as adjudicated by the medical monitor, with failure defined as amputation or gangrene of the target leg or venous thromboembolism-related mortality, and 2) the assessment of PTS severity at the 6-month follow-up visit. In addition to being a component of the primary endpoint, the severity of PTS at 6 months is also evaluated as a stand-alone secondary endpoint. An additional secondary endpoint is a composite of outcomes at the 10-day visit and is structured as a hierarchal win ratio of 1) vessel compressibility on duplex ultrasound, 2) patient-reported pain, and 3) improvement of edema. The safety endpoints are access site complications requiring endovascular or surgical repair and the occurrence through the 30-day visit of mortality, major bleeding, or new symptomatic pulmonary embolism.
DEFIANCE will be the first RCT to evaluate a mechanical thrombectomy-based interventional approach versus anticoagulation therapy alone for DVT. The results will inform the treatment of patients with iliofemoral DVT and the prevention of PTS-associated morbidity.
DEFIANCE: RCT of ClotTriever System Versus Anticoagulation In Deep Vein Thrombosis (DEFIANCE), ClinicalTrials.gov: NCT05701917, URL: https://clinicaltrials.gov/study/NCT05701917?cond=Deep%20Vein%20Thrombosis&term=defiance&rank=1.
深静脉血栓形成（DVT）是一种常见的医学病症，与具有临床意义的后遗症相关，包括血栓形成后综合征（PTS）。对于许多髂股静脉DVT患者，单独抗凝仍然是指南推荐的治疗方法。最近的技术进步导致机械血栓切除术在DVT治疗中的应用增加，但在随机研究中，基于机械血栓切除术的治疗方法尚未与标准的抗凝治疗进行比较。
DEFIANCE研究（ClinicalTrials.gov：NCT05701917）是一项针对下肢DVT的国际、正在积极招募受试者的随机对照试验（RCT），评估一种介入策略，该策略包括使用ClotTriever系统（Inari Medical，尔湾，加利福尼亚州）进行机械血栓切除术与单独抗凝治疗。大约300名单侧髂股静脉DVT且症状持续时间≤12周的患者将按1:1随机分组。研究实施包括一个用于双功超声评估的独立核心实验室、一个用于安全判定的独立医学监测员，以及使用最佳临床实践按照Villalta量表评估PTS严重程度。主要终点是一个复合结局，构建为分层获胜率，包括：1）由医学监测员判定的治疗失败或治疗升级的发生情况，失败定义为目标腿截肢或坏疽或静脉血栓栓塞相关死亡率；2）在6个月随访时对PTS严重程度的评估。除作为主要终点的一个组成部分外，6个月时PTS的严重程度也作为一个独立的次要终点进行评估。另一个次要终点是在10天访视时的复合结局，构建为分层获胜率，包括：1）双功超声检查时血管的可压缩性；2）患者报告的疼痛；3）水肿的改善情况。安全终点是需要血管内或手术修复的穿刺部位并发症以及在30天访视时发生的死亡、大出血或新的有症状肺栓塞。
DEFIANCE将是首个评估基于机械血栓切除术的介入方法与单独抗凝治疗用于DVT的RCT。研究结果将为髂股静脉DVT患者的治疗及PTS相关发病率的预防提供依据。
DEFIANCE：ClotTriever系统与深静脉血栓形成抗凝治疗的RCT（DEFIANCE），ClinicalTrials.gov：NCT05701917，网址：https://clinicaltrials.gov/study/NCT05701917?cond=Deep%20Vein%20Thrombosis&term=defiance&rank=1 。
