PHARMACOMECHANICAL CATHETER-DIRECTED THROMBOLYSIS FOR ACUTE DVT - ATTRACT TRIAL

描述（由申请人提供）：尽管使用标准抗凝治疗，近端深静脉血栓形成（DVT）患者仍经常发生（25-50%）血栓后综合征（PTS）。PTS导致生活方式受限症状、工作残疾、腿部溃疡、生活质量（QOL）损害和主要医疗保健费用。初步研究表明，图像引导的血管内血栓清除术可以快速恢复深静脉通畅，从而预防急性近端DVT患者的PTS。然而，这些研究的局限性在于依赖于临床意义有限的替代解剖结果测量、非随机设计、单中心设计和小样本量。因此，在急性近端DVT的一线治疗中，是否应常规采用血管内血栓清除术，目前医学界存在较大争议。拟议项目的长期目标是确定血管内血栓清除术是否应该在急性深静脉血栓患者中广泛应用。在拟议的研究中，我们将进行一项III期、多中心、开放标签、评估盲法、随机对照试验，题为“急性静脉血栓形成：“用辅助导管定向溶栓（吸引）去除血栓”，以确定是否使用药物力学导管定向溶栓（PCDT），一种最先进的血管内血栓清除方法，导致a)更低的PTS发病率和b)更高的生活质量（QOL），两个临床重要的治疗结果，在有症状的，首发的急性近端DVT患者中。本研究具有创新意义。该研究将是第一个多中心随机试验，以评估最先进的图像引导血管内策略预防PTS。如果该研究为PCDT建立了有利的风险-收益比，这一发现将从根本上改变临床实践，并使成千上万的DVT患者能够预防PTS。如果PCDT不能预防PTS，或者其风险-收益比被证明是不利的，这一发现将减少或取消这种昂贵且具有潜在风险的治疗方法的常规使用。因此，该研究的任何一个结果都将极大地改善临床实践，降低急性深静脉血栓患者的发病率，这是一种常见的血液疾病。因此，这项研究将明显改善公众健康，推进NHLBI的使命。

Description (provided by applicant): Post-Thrombotic Syndrome (PTS) develops frequently (25-50%) in patients with proximal deep vein thrombosis (DVT) despite the use of standard anticoagulant therapy. PTS leads to lifestyle-limiting symptoms, work disability, leg ulcers, quality of life (QOL) impairment, and major healthcare costs. Preliminary studies indicate that image-guided Endovascular Thrombus Removal procedures can rapidly restore deep venous patency and thereby prevent PTS in acute proximal DVT patients. However, these studies are limited by reliance upon surrogate anatomic outcome measures of limited clinical significance, non-randomized design, single-center design, and small sample size. For this reason, there currently exists major controversy within the medical community as to whether or not Endovascular Thrombus Removal should be routinely used in the first-line treatment of acute proximal DVT. The long-term goal of the proposed project is to determine whether Endovascular Thrombus Removal should be translated into widespread, first-line use in patients with acute DVT. In the proposed study, we will conduct a Phase III, multicenter, open label, assessor-blinded, randomized controlled trial entitled "Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis (ATTRACT)" to determine whether the use of Pharmacomechanical Catheter-Directed Thrombolysis (PCDT), a state-of-the-art Endovascular Thrombus Removal method, results in a) a lower prevalence of PTS and b) superior quality of life (QOL), two clinically important treatment outcomes, in symptomatic, first episode, acute proximal DVT patients. The proposed research is both innovative and significant. The study will be the first multicenter randomized trial to evaluate a state-of-the-art image-guided endovascular strategy for the prevention of PTS. If the study establishes a favorable risk-benefit ratio for PCDT, this finding will fundamentally change clinical practice and enable prevention of PTS in thousands of DVT patients. If PCDT does not prevent PTS or if its risk-benefit ratio proves to be unfavorable, this finding will reduce or eliminate the routine use of a costly and potentially risky therapy. Hence, either outcome of the proposed study will greatly improve clinical practice and decrease morbidity in patients with acute DVT, a common blood disorder. Therefore, the study will clearly improve public health and advance the NHLBI's mission. Project Narrative: The ATTRACT Trial will determine whether Pharmacomechanical Catheter-Directed Thrombolysis can prevent the Post-Thrombotic Syndrome (PTS) in patients with Deep Vein Thrombosis (DVT). If the Trial is positive, this finding will conclusively validate the "Open Vein Hypothesis" and thereby a) immediately enable prevention of PTS, a common, morbid, and expensive condition, in thousands of DVT patients each year; and b) catalyze a fundamental shift towards a new treatment paradigm in which early venous thrombus removal is considered an essential element of initial DVT therapy. If the Trial is negative, this finding will eliminate the routine use of a costly and potentially dangerous therapy. Hence, either study outcome will decrease morbidity from DVT, improve public health, and advance the NHLBI's mission.