Hematologic Malignacies, Leukemia, Lymphoma, Multiple Myeloma (MM), Lymphoma, Large B-Cell, Diffuse (DLBCL), Lymphoma, PE - Pulmonary Embolism, Venous Thromboembolic Disease, VTE (Venous Thromboembolism)
Conditions
Keywords
Apixaban, Rivaroxaban, Low-Molecular-Weight Heparin, Venous Thromboembolism, Cancer-Associated Thrombosis, Hematologic Malignancies, Direct Oral Anticoagulants
Brief summary
This study investigates the efficacy and safety of direct oral anticoagulants (DOACs) in comparison with standard low-molecular-weight heparin (LMWH) for the prevention of venous thromboembolism in patients with hematological malignancies. Eligible participants will be randomized to receive reduced-dose apixaban, reduced-dose rivaroxaban, or standard-dose LMWH. The primary objective is to evaluate the incidence of venous thromboembolism during a 6-month follow-up period. Secondary objectives include assessment of bleeding complications, overall survival, and treatment adherence. The results of this study may provide evidence for safer and more convenient thromboprophylaxis strategies in patients with blood cancers.
Detailed description
Patients with hematologic malignancies are at high risk of developing venous thromboembolism (VTE). Low-molecular-weight heparin (LMWH) is currently the standard of care for thromboprophylaxis in this population; however, daily subcutaneous administration is burdensome and may impair adherence. Direct oral anticoagulants (DOACs), such as apixaban and rivaroxaban, have demonstrated efficacy in the prevention and treatment of VTE in patients with solid tumors, but data in hematologic malignancies are limited. This study is designed as a prospective, randomized, open-label, parallel-group trial to compare the efficacy and safety of reduced-dose apixaban and rivaroxaban with standard-dose LMWH in patients with hematologic malignancies requiring primary thromboprophylaxis. Approximately 100 patients will be randomized in a 1:1:1 ratio to receive: Apixaban 2.5 mg orally twice daily, Rivaroxaban 10 mg orally once daily, or LMWH (enoxaparin 40 mg subcutaneously once daily or equivalent). The primary endpoint is the incidence of symptomatic or objectively confirmed VTE within 6 months of randomization. Secondary endpoints include major and clinically relevant non-major bleeding events (as defined by ISTH), treatment adherence, and overall survival at 6 months. This study aims to address the unmet clinical need for optimized, patient-friendly thromboprophylaxis in hematologic malignancies and to provide high-quality data that may guide future clinical practice.
Interventions
DRUGApixaban
Oral tablet, 2.5 mg twice daily, for at least 6 months.
DRUGRivaroxaban
Oral tablet, 10 mg once daily, for at least 6 months.
Subcutaneous injection, 40 mg once daily (or equivalent), for at least 6 months.
Sponsors
Medical University of Gdansk
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Masking description
This is an open-label study; no masking will be applied.
Intervention model description
Patients will be randomized in a 1:1:1 ratio to receive reduced-dose apixaban, reduced-dose rivaroxaban, or standard low-molecular-weight heparin.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Active hematologic malignancy at the time of initiation of systemic therapy, including multiple myeloma, myeloproliferative neoplasm, lymphoma or other hematologic cancer with a Khorana score ≥ 2 points (intermediate or high risk of venous thromboembolism, VTE) * Use of anticoagulant agents for primary thromboprophylaxis, including direct oral anticoagulants (DOACs) at reduced doses (apixaban 2.5 mg twice daily or rivaroxaban 10 mg once daily) or low-molecular-weight heparin (LMWH) (enoxaparin 40 mg subcutaneously once daily).
Exclusion criteria
* Major bleeding within the last month (including gastrointestinal or intracranial bleeding). * Active major bleeding. * Hemoglobin concentration \< 8 g/dL. * Thrombocytopenia with platelet count \<30 × 10⁹/L. * ECOG performance status of 3 or 4. * Expected survival \<6 months. * History of mechanical heart valve or severe mitral stenosis. * Estimated glomerular filtration rate (eGFR) \< 25 mL/min. * Hepatic impairment (ALT ≥ 3× upper limit of normal or bilirubin ≥ 2× upper limit of normal). * Acute coronary syndrome or ischemic stroke within the last 6 months. * Anticipated significant drug-drug interactions between DOACs and anticancer agents. * Known antiphospholipid syndrome (APS).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Venous Thromboembolism (VTE) | 6 months from randomization | Number of patients who develop symptomatic or incidental venous thromboembolism (deep vein thrombosis or pulmonary embolism) confirmed by objective imaging during the study treatment period. |
| Incidence of Major Bleeding (ISTH criteria) | 6 months from randomization | Number of patients experiencing major bleeding as defined by the International Society on Thrombosis and Haemostasis (ISTH). |
| Incidence of Clinically Relevant Non-Major Bleeding (CRNMB) | 6 months from randomization | Number of patients experiencing clinically relevant non-major bleeding (CRNMB) according to ISTH definition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 6 months | Proportion of patients alive at 6 months after randomization. |
| Treatment Discontinuation Due to Adverse Events | 6 months | Number of patients who discontinued study drug due to adverse events, including bleeding and intolerance. |
Countries
Poland
Contacts
Primary ContactAgata Ogłoza-Puchowska, MD
Backup ContactEwa Lewicka, Professor
Outcome results
None listed