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：
9284286
负责人：
Susanne May
金额：
$ 51.48万
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/9284286
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 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 Postoperative Period 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 Statistical Data Interpretation Statistical Models Testing Therapeutic Trials Thrombocytopenia Thrombosis Time 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 public health relevance 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（由适用提供）：尽管血小板输血疗法取得了重大进展，但由于化学疗法引起的骨髓性增长症和造血干细胞疾病，血小板减少症患者的出血仍然是一个问题。出血率似乎不会受到血小板输血阈值的影响，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，大约70％的受试者发生了2级出血，无论血小板剂量输了什么。同样，在600例治疗与预防性血小板的患者试验中输血（TOPPS），出血仍然是一个常见事件。预扣输血可能导致严重和致命的出血。由于严重血小板减少症和重症患者的血小板存活缩短，因此很难维持安全的血小板计数。患者对血小板输血的难治可能需要昂贵且难以获得匹配的血小板。维持在门诊患者中规定的触发器上方的血小板计数可能需要日常实验室工作和经常转移。用于降低出血的其他手段包括用抗纤维蛋白水解剂进行治疗，该毒剂多年和积极地用于血小板功能和血小板功能和凝结缺陷（例如血友病）的患者。令人鼓舞的是预防或治疗血小板减少性出血的抗纤维蛋白水解药物的报道令人鼓舞，并建议在许多患者中可以预防或停止出血。这种轶事回顾性单中心报告导致许多医生在血小板减少患者对血小板输血的难治性中开出抗纤维蛋白水解剂。但是，缺乏效率和安全性的证据阻止了这一标准的护理标准。纤维蛋白溶解抑制剂EPSILON氨基酸氨基酸（EACA）的关键研究将通过导致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方法。我们计划进行一项前瞻性，随机，安慰剂对照试验，以评估EACA治疗因原发性骨髓疾病或化学疗法，免疫疗法和/或放射疗法而导致的EACA治疗以防止患者血小板减少患者出血的有用性。这项研究将通过提供证据表明EACA在用作血小板输血疗法的辅助方面是否有效和安全来改变实践。这些目标太比较了继发于原发性骨髓疾病，HSCT或化学疗法，免疫疗法和/或放射随机的血小板减少症患者的出血，输血和血栓形成的30天发电，随机接受EACA或安慰剂。研究设计是一项双盲，随机，安慰剂对照试验。可能会使用图表审查，受试者访谈和身体检查，每天将在每天的住院医师每天进行筛选，以进行5天的血小板计数= 10,000/µL = 5天的受试者将进行筛查，并且血栓形成评估将进行。门诊受试者每天将保持日记，并至少每周在诊所中看到。