Safety and efficacy of a D-Dimer-guided strategy for extension of secondary prophylaxis of venous thromboembolism - a prospective and randomized management trial

急性深静脉血栓（DVT）首次发作后复发的风险相对较高，临床后果很重要。因此，在这些患者中通常采用口服抗凝治疗（OAT）进行二级预防。这种治疗非常有效地降低了复发的风险，但会增加出血的风险。主要出血并发症的发生率为2%。因此，目前的建议将OAT的期限限制在3至12个月。然而，在停止OAT治疗后，10%的无因性深静脉血栓患者将在1年内复发。这组患者可能受益于延长OAT。两项独立观察性研究的结果显示，停用OAT后d -二聚体水平升高的患者复发风险显著增加。d -二聚体是一种生物标志物，表明纤维蛋白形成后纤维蛋白溶解。基于这些数据，我们假设d -二聚体检测可以成功地用于调整无诱因深静脉血栓发作后患者的OAT持续时间。本临床试验将采用前瞻性、随机和对照设计来研究这一假设。大约300名患者在停用OAT后显示d -二聚体增加（> 500 ng/ml），将被随机分配到治疗组和非治疗组。在24个月的持续治疗期间，客观记录的DVT/肺栓塞率（主要疗效终点）和出血率（主要安全性终点）将被记录下来。持续12个月的随访期将显示停止延长OAT后是否出现追赶现象。结果将显示基于d -二聚体的治疗算法是否可以实施到临床实践中。

After a first episode of acute deep venous thrombosis (DVT) the risk of recurrence is relatively high and clinical consequences are important. Therefore, secondary prophylaxis using oral anticoagulant treatment (OAT) is usually established in these patients. This treatment very effectively reduces the risk of recurrences but induces an increased risk of bleeding. Major bleeding complications can be expected in »2% patient-years. Therefore, current recommendations limit OAT to a period of 3 to 12 months. After stopping of OAT, however, »10 % of patients with an initial episode of unprovoked DVT will develop a recurrent event within 1 year. This group of patients may benefit from prolonged OAT. The results of 2 independent observational studies showed a significantly higher risk of recurrence in patients showing increased levels of D-Dimer after withdrawal of OAT. D-Dimer is a biomarker that indicates fibrin formation followed by fibrinolysis. Based on these data we hypothesize that D-Dimer testing can be successfully used to tailor the duration of OAT in patients after an unprovoked episode of DVT. This clinical trial will investigate this hypothesis using a prospective, randomized, and controlled design. Approximately 300 patients showing increased D-Dimer (> 500 ng/ml) after withdrawal of OAT will be randomly assigned to a treatment and a non-treatment group. During a 24-months lasting treatment period the rates of objectively documented DVT/pulmonary embolism (primary efficacy endpoint) and of hemorrhages (primary safety endpoint) will be documented. A 12-months lasting follow up period will show whether a catch-up phenomenon occurs after stopping of extended OAT. The results will show if D-Dimer-based treatment algorithms can be implemented into clinical practice.