Trial Using Epsilon Aminocaproic Acid Therapy in Thrombocytopenia - DCC

 描述(申请人提供)：尽管血小板输注疗法取得了重大进展，但由于化疗引起的骨髓再生障碍性贫血和造血干细胞疾病而导致的血小板减少症患者，出血仍然是一个问题。出血发生率似乎不受提高血小板输注阈值的影响，当血小板计数高于5,000/µL时，出血发生率似乎不依赖于血小板计数。在对1,272名患者进行的PLADO(血小板剂量)试验中，无论输注血小板剂量如何，约70%的受试者发生世卫组织2级出血。类似地，在一项600名患者的治疗性与预防性血小板试验中也是如此 输血(TOPS)、出血仍是常见事件。停止输血可能会导致严重和致命的出血。由于严重的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是困难的。对血小板输注无效的患者可能需要昂贵且难以获得匹配的血小板。 将门诊患者的血小板计数维持在规定的触发水平以上可能需要日常的实验室工作和频繁的输血。其他用于减少出血的方法包括术中和术后多年使用的抗纤溶药物治疗，以及有血小板功能和凝血缺陷的患者，如血友病。抗纤溶药物预防或治疗血小板减少性出血的报道令人鼓舞，并表明在许多患者中，出血是可以预防或停止的。这种坊间的、回顾性的单中心报告导致许多内科医生给血小板输注无效的血小板减少患者开出抗纤溶药物。然而，缺乏有效性和安全性的证据阻碍了这一成为护理的标准。一项关键的氨基己酸(EACA)研究将通过引导医生采用或放弃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疗法预防因原发骨髓疾病或化疗、免疫治疗和/或放射治疗引起的血小板减少患者出血的有效性。这项研究将改变实践，提供证据，证明EACA作为血小板输注治疗的辅助手段是否有效和安全。目的也是比较因原发骨髓疾病、HSCT或化疗、免疫治疗和/或随机接受EACA或安慰剂治疗而继发的低增殖性血小板减少症患者30天内出血、输血和血栓形成的发生率。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出血筛查，并将通过图表复习、受试者访谈和体检每天对住院患者进行血栓形成评估。门诊受试者将每天写日记，并至少每周在诊所看到一次。

 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.