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

基本信息

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
项目类别：
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

项目摘要

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。出血发生率似乎并未受到血小板输注阈值增加的影响。在 1272 的 PLADO（血小板剂量）试验中，当血小板计数高于 5,000/μl 时，似乎不依赖于血小板计数。在一项 600 名患者的治疗性血小板与预防性血小板试验中，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。输血（TOPPS）时，停止输血可能会导致严重和致命的出血，因为严重血小板减少症和危重患者的血小板存活时间可能会缩短。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点以上可能需要每天进行实验室检查和频繁输血，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以及患有血小板功能和凝血缺陷的患者中使用多年。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，表明许多患者的出血是可以预防或停止的，这种轶事、回顾性单中心报告引起了许多医生的关注。为难治性血小板输注的血小板减少症患者开具抗纤维蛋白溶解药物，但缺乏有效性和安全性证据，阻止其成为护理标准。对纤维蛋白溶解抑制剂 Epsilon Aminocaproic Acid (EACA) 的一项关键研究将改善领先医生对患者的护理。采用它或放弃它的使用作为预防血小板减少性出血的治疗方法，我们计划进行一项前瞻性、随机、安慰剂对照试验，评估 EACA 疗法在预防原发性骨髓疾病或化疗、免疫治疗和/或放射治疗引起的血小板减少症患者中的有效性。将通过提供 EACA 作为血小板输注治疗的辅助疗法是否有效和安全的证据来改变实践。目标也是比较 30 天出血、输血和血栓形成患者的发生率。继发于原发性骨髓疾病、HSCT 或化疗、免疫治疗和/或放射治疗的随机接受 EACA 或安慰剂的低增殖性血小板减少症该研究设计是一项双盲、随机、安慰剂对照试验，受试者的血小板计数可能为 =10,000/μl。持续=5天的患者将接受资格筛查。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，门诊患者将每天记录日记并在以下时间就诊。至少每周一次去诊所。