American Trial Using Tranexamic Acid in Thrombocytopenia (A-TREAT) - DCC

 描述（由申请人提供）：尽管血小板输注治疗取得了重大进展，但由于化疗诱导的骨髓再生障碍和造血干细胞疾病导致的血小板减少症患者的出血仍然是一个问题。出血发生率似乎不受增加血小板输注阈值的影响，并且当血小板计数高于5，000/µl时，似乎不依赖于血小板计数。在1272例患者的PLADO（血小板剂量）试验中，无论输注的血小板剂量如何，约70%的受试者发生WHO 2级出血。同样，在一项600例患者的治疗性与预防性血小板试验中， 输血（TOPPS），出血仍然是常见事件。停止输血可能导致严重和致命的出血。由于严重血小板减少和危重患者的血小板存活时间缩短，维持安全的血小板计数可能很困难。血小板输注难治的患者可能需要昂贵且难以获得匹配的血小板。 维持血小板计数高于规定的触发在门诊患者可能需要每天的实验室工作和频繁的输血。用于减少出血的其他方法包括使用抗纤维蛋白溶解剂治疗，在术中和术后以及患有血小板功能和凝血缺陷（如血友病）的患者中使用多年。抗纤溶药物预防或治疗血小板减少性出血的报告令人鼓舞，并表明许多患者的出血可以预防或停止。此类轶事性、回顾性单中心报告导致许多医生在血小板输注难治性血小板减少症患者中开具抗纤溶药物。然而，缺乏有效性和安全性的证据阻止其成为标准治疗。一项关于纤维蛋白溶解抑制剂表氨基己酸（EACA）的关键性研究将通过引导医生采用或放弃其使用来改善患者护理 作为预防血小板减少性出血的治疗。我们计划进行一项前瞻性、随机、安慰剂对照试验，评估EACA治疗对预防原发性骨髓疾病或化疗、免疫治疗和/或放疗所致血小板减少患者出血的有效性。这项研究将通过提供证据来证明EACA作为血小板输注治疗的辅助治疗是否有效和安全，从而改变实践。目的也是比较原发性骨髓疾病、HSCT或化疗、免疫治疗和/或放疗继发低增殖性血小板减少症患者随机接受EACA或安慰剂治疗的30天出血、输血和血栓形成发生率。研究设计为双盲、随机、安慰剂对照试验。将对血小板计数≥ 10，000/µl ≥ 5天的受试者进行合格性筛选。将通过病历审查、受试者访谈和体格检查，每天对住院患者进行出血和血栓形成评估。门诊受试者将每天记录日记，并至少每周在门诊就诊。

 DESCRIPTION (provided by applicant): Despite major advances in platelet transfusion therapy, bleeding remains a problem in patients with thrombocytopenia due to chemotherapy induced marrow aplasia and hematopoietic stem cell disorders. Bleeding incidence does not appear to be affected by increasing the platelet transfusion threshold and does not appear to be dependent on the platelet count when it is above 5,000/µl. In the PLADO (Platelet Dose) Trial of 1272 patients, WHO grade 2 bleeding occurred in approximately 70% of subjects regardless of platelet dose transfused. Similarly in a 600 patient trial of therapeutic vs. prophylactic platelet transfusion (TOPPS), bleeding remained a common event. Withholding transfusion may lead to serious and fatal bleeding. Maintenance of a safe platelet count may be difficult due to shortening of platelet survival in severely thrombocytopenic and critically ill patients. Patients refractory to platelet transfusion may require expensive and difficult to obtain matched platelets. Maintenance of the platelet count above a prescribed trigger in outpatients may require daily laboratory work and frequent transfusions. Other means used to decrease bleeding include treatment with antifibrinolytic agents, used for years intra- and postoperatively and in patients with platelet function and coagulation defects such as hemophilia. Reports of antifibrinolytic drugs to prevent or treat thrombocytopenic bleeding are encouraging and suggest that in many patients bleeding can be prevented or stopped. Such anecdotal, retrospective single center reports lead many physicians to prescribe antifibrinolytic agents in thrombocytopenic patients refractory to platelet transfusions. However lack of evidence of efficacy and safety prevent this becoming standard of care. A pivotal study of Epsilon Aminocaproic Acid (EACA), an inhibitor of fibrinolysis, will improve patient care by leading physicians to either adopt it or abandon its use as treatment for prevention of thrombocytopenic bleeding. We plan to conduct a prospective, randomized, placebo controlled trial evaluating the usefulness of EACA therapy to prevent bleeding in patients thrombocytopenic due to primary bone marrow disorders or chemotherapy, immunotherapy and/or radiation therapy. This study will change practice by providing evidence as to whether EACA is effective and safe when used as an adjunct to platelet transfusion therapy. The objectives are too compare the 30 day incidences of bleeding, transfusion, and thrombosis in patients with hypoproliferative thrombocytopenia secondary to primary marrow disorder, HSCT, or chemotherapy, immunotherapy and/or radiation randomized to receive EACA or placebo. The study design is a double blind, randomized, placebo controlled trial. Subjects likely to have platelet counts of =10,000/µl for =5 days will be screened for eligibility Bleeding and thrombotic assessments will be performed on inpatients daily using chart review, subject interview and physical examination. Outpatient subjects will maintain a diary daily and be seen at least weekly in clinic.