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

美国使用氨甲环酸治疗血小板减少症的试验 (A-TREAT) - DCC

• 批准号: 9123668
• 负责人: Scott S Emerson
• 金额: $ 50.77万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9123668
• 关键词: 6-Aminocaproic Acid; Accounting; Achievement; Address; Adherence; Adopted; Affect; Amendment; American; Antifibrinolytic Agents; Blinded; Blood; Blood Platelets; Blood coagulation; Bone Marrow Diseases; Case Report Form; Clinic; Clinical; Clinical Trials; Clinical Trials Data Monitoring Committees; Coagulation Process; Collaborations; Communities; Critical Illness; Data; Data Coordinating Center; Data Set; Defect; Development; Dictionary; Disease; Dose; Double-Blind Method; Eligibility Determination; Ensure; Event; Fibrinolysis; Funding; Funding Agency; Future; Goals; Health; Hematopoietic stem cells; Hemophilia A; Hemorrhage; Hospitals; Human Resources; Immunotherapy; Incidence; Informatics; Information Dissemination; Inpatients; Institutional Review Boards; Interview; Investigation; Knowledge; Laboratories; Lead; Letters; Link; Maintenance; Manuals; Manuscripts; Marrow; Meta-Analysis; Methods; Monitor; National Health Services; National Heart, Lung, and Blood Institute; Online Systems; Outpatients; Patient Care; Patients; Pharmaceutical Preparations; Phase; Physical Examination; Physicians; Placebos; Platelet Count measurement; Platelet Transfusion; Preparation; Prevention; Procedures; Protocols documentation; Radiation; Radiation therapy; Randomized; Recruitment Activity; Refractory; Reporting; Research; Research Design; Research Personnel; Safety; Sample Size; Sampling; Secondary to; Site Visit; Source; Staging; Statistical Data Interpretation; Statistical Models; Testing; Therapeutic Trials; Thrombocytopenia; Thrombosis; Training; Tranexamic Acid; Transfusion; Transplantation; United Kingdom; Universities; Washington; Work; Writing; arm; base; chemotherapy; clinical research site; data management; design; diaries; experience; human subject; improved; inhibitor/antagonist; operation; patient population; placebo controlled study; prevent; professor; prophylactic; prospective; randomized placebo controlled trial; randomized trial; sound; standard of care; treatment effect

 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.

 描述（由申请人提供）：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和造血干细胞紊乱，出血仍然是血小板减少症患者的一个问题。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，出血发生率似乎不依赖于血小板计数。在 1272 名患者参与的 PLADO（血小板剂量）试验中，无论输注的血小板剂量如何，大约 70% 的受试者发生了 WHO 2 级出血。同样，在一项 600 名患者参与的治疗性血小板与预防性血小板试验中 输血（TOPPS）、出血仍然是常见事件。停止输血可能会导致严重和致命的出血。由于严重血小板减少症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。难治性血小板输注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值以上可能需要日常实验室工作和频繁输血。用于减少出血的其他方法包括抗纤维蛋白溶解药物治疗，该药物在术中和术后使用多年，适用于患有血小板功能和血友病等凝血缺陷的患者。关于使用抗纤维蛋白溶解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是可以预防或停止的。这种轶事、回顾性单中心报告导致许多医生为血小板输注难治的血小板减少症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其成为护理标准。对纤维蛋白溶解抑制剂 Epsilon Aminocaproic Acid (EACA) 的一项关键研究将引导医生采用或放弃其使用，从而改善患者护理 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 疗法预防原发性骨髓疾病或化疗、免疫疗法和/或放射疗法引起的血小板减少症患者出血的有效性。这项研究将通过提供证据证明 EACA 在用作血小板输注治疗的辅助疗法时是否有效且安全，从而改变实践。目的还比较了继发于原发性骨髓疾病、HSCT 或化疗、免疫治疗和/或放射随机接受 EACA 或安慰剂的低增殖性血小板减少症患者 30 天出血、输血和血栓形成的发生率。该研究设计是一项双盲、随机、安慰剂对照试验。将筛选血小板计数可能为 =10,000/μl 且持续 =5 天的受试者的资格。每天将使用图表审查、受试者访谈和体检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日记并至少每周去诊所就诊。