PHARMACOMECHANICAL CATHETER-DIRECTED THROMBOLYSIS FOR ACUTE DVT - ATTRACT TRIAL

描述(由申请人提供)：血栓后综合征(PTS)在近端深静脉血栓形成(DVT)患者中经常发生(25%-50%)，尽管使用了标准的抗凝治疗。PTS会导致生活方式受限症状、工作残疾、腿部溃疡、生活质量(QOL)受损和重大医疗成本。初步研究表明，影像引导下的血管内血栓清除手术可以迅速恢复深静脉通畅，从而预防急性近端DVT患者的PTS。然而，这些研究受到以下因素的限制：依赖临床意义有限的替代解剖结果测量、非随机设计、单中心设计和样本量小。因此，目前医学界对急性近端深静脉血栓的一线治疗是否应常规使用血管内血栓取出术存在较大争议。拟议项目的长期目标是确定血管内血栓清除是否应该转化为在急性DVT患者中广泛、一线使用。在这项拟议的研究中，我们将进行一项名为“急性静脉血栓形成：辅助导管定向溶栓(CATIL)”的第三阶段多中心、开放标签、评估者盲法随机对照试验，以确定药物机械导管定向溶栓(PCDT)的使用是否导致a)较低的PTS患病率和b)较高的生活质量(QOL)，这两个临床重要的治疗结果在有症状的首次发作的急性近端DVT患者中出现。本文提出的研究具有创新性和重要意义。这项研究将是第一个评估最先进的影像引导血管内策略预防PTS的多中心随机试验。如果这项研究为PCDT建立了一个有利的风险-收益比，这一发现将从根本上改变临床实践，并使数千名DVT患者能够预防PTS。如果PCDT不能预防PTS，或者如果它的风险-收益比被证明是不利的，这一发现将减少或取消常规使用昂贵和潜在风险的治疗。因此，建议的研究结果中的任何一项都将极大地改善临床实践，降低急性DVT患者的发病率，急性DVT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。 项目简介：CATRACT试验将确定药物机械导管定向溶栓是否可以预防深静脉血栓(DVT)患者的血栓后综合征(PTS)。如果试验是阳性的，这一发现将最终证实“开放静脉假说”，从而a)立即能够在每年数千名DVT患者中预防PTS，这是一种常见、病态和昂贵的疾病；以及b)催化向新的治疗模式的根本转变，在这种治疗模式中，早期静脉血栓清除被认为是初始DVT治疗的基本要素。如果试验结果为阴性，这一发现将消除常规使用昂贵且具有潜在危险的疗法。因此，任何一项研究结果都将降低DVT的发病率，改善公共健康，并推进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.