PROBLEMA 2014.

Trial name or title	Randomized Trial of Epsilon Aminocaproic Acid Versus Platelet Transfusions for the Prevention of Bleeding in Thrombocytopenic Patients With Hematological Malignancies (PROBLEMA) (NCT02074436)
Methods	Single‐centre (USA), randomised parallel, open‐label study Duration of patient participation: 6 months
Participants	Inclusion Criteria: Age > 18 years with a haematological malignancy Informed consent Thrombocytopenia with platelet counts < 20 x 10⁹/L in the outpatient or < 10 x 10⁹/L in the inpatient and one of the following criteria. Acute thrombocytopenia in people with haematological malignancies in remission receiving myelosuppressive consolidation chemotherapy that is expected to induce marrow aplasia for at least 2 weeks or; Chronic thrombocytopenia in people with newly diagnosed marrow failure syndromes, myelodysplastic syndromes, aplastic anaemia,chronic myelomonocytic leukaemia or myelofibrosis or; Chronic thrombocytopenia in people with relapsed or refractory hematological malignancy or; Haematopoietic stem cell transplant recipients with chronic thrombocytopenia due to chronic graft versus host disease (GVHD) or other Exclusion Criteria: APML Person receiving anticoagulation Person receiving antiplatelet or antifibrinolytic agents Person receiving procoagulant agent including 1‐deamino‐8‐D‐arginine vasopressin (DDAVP), recombinant factor VIIa or prothrombin complex concentrate within 24 hours of enrolment Person with known congenital bleeding disorders or platelet dysfunction DIC Fibrinogen level < 150 mg/dL Person with known lupus anticoagulant or positive antiphospholipid antibody History of arterial or venous thromboembolic disease 6 months prior to screening Person requiring platelet transfusion threshold of > 20 x 10⁹/L Active WHO grade ≥ 2 bleeding at the time of randomisation, including haematuria History of WHO grade 4 bleeding Haematopoietic stem cell transplant recipient within 100 days posttransplant Pregnancy Known allergy to EACA History of veno‐occlusive disease of the liver Myocardial infarction 6 months prior to screening
Interventions	Intervention: Prophylactic EACA 1000 mg PO twice daily if platelet count < 20 x 10⁹/L. Additional platelet transfusion will be administered in case of WHO grade 3 or 4 bleeding. Comparator: Platelet transfusion if platelet count is < 20 x 10⁹/L. Additional platelet transfusion will be administered in case of grade 3 or 4 bleeding.
Outcomes	Primary outcome: Proportion of patients who develop major bleeding episodes (WHO grades 3 or 4) [ Time Frame: 6 months ] Secondary outcomes: Proportion of patients with any bleeding during the study period in each arm The total number of units of platelets transfused in each arm at the end of the study QoL as measured in each arm before the study and at the end of the study Safety in each arm
Starting date	May 2014
Contact information	Ana G. Antun, MD 4045936732 ana.antun@emoryhealthcare.org Ann Shen, CRN 4047785982 ann.shen@emory.edu Emory University Hospital Atlanta, Georgia, United States, 30322
Notes	Planned enrolment: 100 Planned study completion: May 2017