Randomized Trial of Epsilon Aminocaproic Acid Versus Platelet Transfusions for the Prevention of Bleeding in Thrombocytopenic Patients With Hematological Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 29
- 试验地点
- 2
- 主要终点
- Percentage of Participants Who Develop Major Bleeding Episodes
研究概览
简要总结
STUDY BACKGROUND AND PURPOSE:
Patients with hematological malignancies (blood-related cancers) often develop thrombocytopenia (low platelet count), which can be made worse by cancer treatment.
Preventive (prophylactic) platelet transfusion remains the standard of care for thrombocytopenic patients. However, bleeding remains a significant problem in these patients, affecting approximately 20% of patients with acute myeloid leukemia and 34-58% of hematopoietic stem cell transplant recipients. Platelet transfusion refractoriness, the repeated failure to obtain satisfactory response to platelet transfusions, is a common problem. Alternatives to platelet transfusions are desperately needed for these patients.
Epsilon aminocaproic acid (EACA) blocks a process called fibrinolysis that is an essential step in the bleeding process. EACA is approved by the FDA for the treatment of severe bleeding-related diseases and complications. A small study has shown EACA to be well tolerated and associated with low risk of bleeding in patients with hematological malignancies.
This study will compare EACA versus standard prophylactic platelet transfusion for the prevention of bleeding in thrombocytopenic patients with hematological malignancies.
STUDY DESCRIPTION:
This is Phase II study to compare EACA versus standard prophylactic platelet transfusion to prevent bleeding in thrombocytopenic patients with hematological malignancies. Patients who are eligible to take part must give their written agreement before they can be enrolled.
The study will enroll 100 patients who will be assigned randomly to take EACA twice daily or to undergo standard prophylactic platelet transfusion. Patients will be followed for any bleeding events, need for platelet transfusion, and any side effects experienced. Patients will complete questionnaires to assess their quality of life while on the study.
详细描述
Study Treatments: Epsilon aminocaproic acid (EACA) vs. standard prophylactic platelet transfusions.
Study Title: Randomized Trial of Epsilon Aminocaproic Acid versus Platelet Transfusions for the Prevention of Bleeding in Thrombocytopenic Patients with Hematological Malignancies. (PROBLEMA trial: PRevention Of BLeeding in hEmatological Malignancies with Antifibrinolytic agents (epsilon aminocaproic acid).
Phase: Randomized Phase 2
Eligible Population: Adult patients with acute or chronic thrombocytopenia in the setting of hematological malignancies.
Summary and Study Rationale: Compare EACA to standard prophylactic platelet transfusion for the prevention of bleeding in thrombocytopenic patients with hematological malignancies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 18 with a hematological malignancy
- •Informed consent
- •Thrombocytopenia with untransfused platelet counts < 20 x 10⁹/L in the out-patient or in the in-patient setting and one of the following criteria:
- •Acute thrombocytopenia in patients with hematological malignancies who are in remission and are receiving myelosuppressive consolidation chemotherapy that is expected to induce marrow aplasia for at least 2 weeks; or
- •Acute or chronic thrombocytopenia in patients with acute leukemia (myeloblastic or lymphoblastic) receiving induction or re-induction chemotherapy that is expected to induce marrow aplasia for at least 2 weeks; or
- •Expected chronic thrombocytopenia in patients with newly diagnosed marrow failure syndromes, myelodysplastic syndromes, aplastic anemia, chronic myelomonocytic leukemia or myelofibrosis; or
- •Expected chronic thrombocytopenia in patients with relapsed or refractory hematological malignancies; or
- •Hematopoietic stem cell transplant recipients with chronic thrombocytopenia due to chronic graft-versus-host disease (GVHD) or other causes
排除标准
- •Acute promyelocytic leukemia
- •Patient receiving anticoagulation
- •Patient receiving antiplatelet agents
- •Patient treated with antifibrinolytic agents (including EACA) within 14 days prior to screening
- •Subjects receiving procoagulant agent including DDAVP, recombinant factor VII or prothrombin complex concentrate within 24 hours of enrollment
- •Subject with known congenital bleeding disorders or platelet dysfunction
- •Disseminated intravascular coagulation
- •Fibrinogen level < 150 mg/dl
- •Patients with known lupus anticoagulant or positive antiphospholipid antibody
- •History of arterial or venous thromboembolic disease 6 months prior to screening
- •Patient requiring platelet transfusion threshold of > 20 x 10⁹/L
- •Active grade ≥ 2 bleeding at the time of randomization, including hematuria
- •History of grade 4 bleeding
- •Hematopoietic stem cell transplant recipient within 100 days post-transplant
- •Pregnancy
- •Known allergy to EACA
- •History of veno-occlusive disease of the liver
- •Myocardial infarction 6 months prior to screening
- •Unstable angina
- •Grade 2 renal dysfunction: creatinine > 2-3 times the upper limit of normal
研究组 & 干预措施
Prophylactic EACA
Prophylactic EACA 1000 mg PO twice daily if platelets < 20 x 10⁹/L
干预措施: EACA (Drug)
Platelet transfusion
Platelet transfusion if platelet count is < 20 x 10⁹/L in the outpatient or < 10 x 10⁹/L in the inpatient setting
干预措施: Platelet transfusion (Other)
结局指标
主要结局
Percentage of Participants Who Develop Major Bleeding Episodes
时间窗: 6 months
The primary objective of this study is to compare the percentage of patients who develop major bleeding episodes (WHO grades 3-4) in the group randomized to receive prophylactic EACA versus standard of care prophylactic platelet transfusions. Grade 3 bleeding is defined as a bleed that significantly limits the patient's ability to perform routine activities despite symptomatic therapy and leads to reduction of the dose or discontinuation of the study drug. Grade 4 bleeding is a life-threatening bleed that requires discontinuation of the study drug and the patient is at immediate risk of death
次要结局
未报告次要终点
研究者
Ana G. Antun
Principal Investigator
Emory University