Testing a Novel Approach to Chemotherapy-Associated Thrombocytopenia

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

NCT02578901

National Heart, Lung, and Blood Institute

University of Pittsburgh, University of North Carolina, University of Washington

330 patients

In this double-blind, randomized, placebo-controlled trial, patients who are likely to have platelet counts of ≤10,000/µL for ≥ five days are assigned receive either the antifibrinolytic agent, tranexamic acid (TXA), or placebo. The thrombocytopenia must be hypoproliferative, secondary to primary marrow disorders, chemotherapy, immunotherapy, radiation and/or hematopoietic stem cell transplant. The dose of TXA is 1.0 g intravenously or 1.3 g by mouth every eight hours. Study medication is initiated once the platelet count drops below 30,000/µL, and the study period continues until the count is greater than or equal to 30,000/µL for three consecutive days without transfusion support or for 30 days after initiation, whichever is shorter. The primary endpoints are bleeding and thrombosis throughout the study period or 30 days after initiation of study drug. Assessments will be performed daily on inpatient subjects via chart review, subject interview and physical examination. Outpatient subjects will maintain a daily diary and be seen at least weekly in clinic.

The majority of patients with thrombocytopenia due to chemotherapy-induced marrow aplasia and primary hematopoietic stem cell disorders will experience bleeding at some point during the treatment course. While most of this bleeding is low grade, rates increase significantly when the platelet count drops below 5,000/µL, and the majority of patients require one or more platelet transfusions to remain safely above this threshold. Keeping the platelet count above any threshold is often challenging for several reasons, and even low-grade bleeding can have a negative impact on patient quality of life and resource utilization. Any intervention that could reduce rates of bleeding and/or platelet transfusions would have major safety and cost-saving implications. ε-aminocaproic acid (EACA) and TXA are inhibitors of fibrinolysis that can be given either intravenously or orally.

The possibility that antifibrinolytic agents, which can be given either intravenously or orally, could lower the risk of bleeding and/or reduce the use of donor platelets is exciting but unproven. This pivotal, well-designed randomized trial will test the hypothesis that tranexamic acid is a safe and effective treatment for patients with thrombocytopenia due to chemotherapy-related myelotoxicity or a primary hematopoietic stem cell disorder. In addition to determining whether the number of platelet transfusions or bleeding episodes is reduced, the study will provide key evidence as to whether TXA affects any clinically important increase in the risk of thrombosis.