A Phase II Multicenter Trial With Rivaroxaban in the Treatment of Livedoid Vasculopathy Assessing Pain on a Visual Analog Scale
A Phase II Multicenter Trial With Rivaroxaban in the Treatment of Livedoid Vasculopathy Assessing Pain on a Visual Analog Scale
复制标题
使用利伐沙班治疗青斑血管病的 II 期多中心试验，通过视觉模拟量表评估疼痛
作者：
A. Drabik;Carina Hillgruber;T. Goerge
背景青斑样血管病是一种以皮肤微循环反复血栓形成为特征的罕见皮肤病。它几乎只出现在脚踝、足背和小腿远端。由于血管闭塞，患者遭受强烈的局部缺血性疼痛。青斑样血管病变的发病率估计约为1：100，000。目前还没有批准的青斑样血管病变的治疗方法，使标签外治疗成为唯一的选择。在欧洲，低分子肝素的血栓预防治疗已被广泛接受。目的本试验的目的是统计学验证抗凝剂利伐沙班治疗青斑样血管病变的疗效。方法我们进行了一项治疗性IIa期试验，设计为前瞻性、单臂、多中心、干预性病例系列，计算样本量为20例患者。主要结局是根据视觉模拟量表（VAS）评估局部疼痛，基线和12周之间的个体内差异为2个值。结果入组于2012年12月开始，在提交之日仍处于开放状态。这项研究预计将于2014年11月完成。结论青斑样血管病变与皮肤微循环血栓形成有关，持续应用抗凝剂有助于改善症状。皮肤梗死的原因是异质性的，但最终遵循已知的凝血级联机制。利伐沙班影响凝血级联反应并抑制凝血因子Xa依赖性的凝血酶原转化为凝血酶，从而显著降低血栓形成的风险。试验注册试验注册EudraCT编号：2012-000108-13-DE; https://www.clinicaltrialsregister.eu/ctr-search/search? query=eudract_number：2012-000108-13（WebCite存档，网址：http：//www.webcitation.org/6UCktWVCA）;德国临床试验注册中心（DRKS）：DRKS 00004652; https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do? navigationId=trial.HTML&TRIAL_ID= DRKS 00004652（由WebCite在http：//www.webcitation.org/6UCIAKYCS存档）。
Background Livedoid vasculopathy is an orphan skin disease characterized by recurrent thrombosis of the cutaneous microcirculation. It manifests itself almost exclusively in the ankles, the back of the feet, and the distal part of the lower legs. Because of the vascular occlusion, patients suffer from intense local ischemic pain. Incidence of livedoid vasculopathy is estimated to be around 1:100,000. There are currently no approved treatments for livedoid vasculopathy, making off-label therapy the only option. In Europe, thromboprophylactic treatment with low-molecular-weight heparins has become widely accepted. Objective The aim of this trial is the statistical verification of the therapeutic effects of the anticoagulant rivaroxaban in patients suffering from livedoid vasculopathy. Methods We performed a therapeutic phase IIa trial designed as a prospective, one-armed, multicenter, interventional series of cases with a calculated sample size of 20 patients. The primary outcome is the assessment of local pain on the visual analog scale (VAS) as an intraindividual difference of 2 values between baseline and 12 weeks. Results Enrollment started in December 2012 and was still open at the date of submission. The study is expected to finish in November 2014. Conclusions Livedoid vasculopathy is associated with increased thrombophilia in the cutaneous microcirculation and the continuous use of anticoagulants helps improve the symptoms. The causes of cutaneous infarctions are heterogenous, but ultimately follow the known mechanisms of the coagulation cascade. Rivaroxaban affects the coagulation cascade and inhibits the factor Xa–dependent conversion of prothrombin to thrombin, thereby considerably reducing the risk of thrombosis. Trial Registration Trial Registration EudraCT Number: 2012-000108-13-DE; https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000108-13 (Archived by WebCite at http://www.webcitation.org/6UCktWVCA); German Clinical Trials Register (DRKS): DRKS00004652; https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00004652 (Archived by WebCite at http://www.webcitation.org/6UCIAKyCS).