Trial Results

The Hokusai-VTE Trial was the largest single VTE trial to date—and the only VTE trial to prospectively evaluate factors that increase bleeding risk* and allow for a dose reduction in eligible patients 1,2

Trial Design1

Trial Overview1

    • Patients 18 years of age or older were eligible if they had objectively diagnosed, acute, symptomatic deep-vein thrombosis involving the popliteal, femoral, or iliac veins or acute, symptomatic pulmonary embolism (with or without deep-vein thrombosis)
    • Patients were excluded if they had contraindications to heparin or warfarin, had received treatment for more than 48 hours with therapeutic doses of heparin, had received more than one dose of a vitamin K antagonist, had cancer for which long-term treatment with low-molecular-weight heparin was anticipated, had another indication for warfarin therapy, continued to receive treatment with aspirin at a dose of more than 100 mg daily or dual antiplatelet therapy, or had creatinine clearance of less than 30 ml per minute
    • Flexible 3- to 12-month treatment duration
    • Included a well-managed warfarin comparator, with patients in the therapeutic INR range of 2.0 to 3.0 for 63.5% of the time (median time in therapeutic range)

Patient Baseline Characteristics1

The Hokusa-VTE Trial studied a broad range of eligible patients, including a high percentage of patients with varying disease severities or other factors that increase bleeding risk.1,4

  • Patient baseline characteristics were well balanced across study arms1
  • Eligible patients may have had one or more of the above comorbidities or other factors that increase bleeding risk1

Flexible 3- to 12-month treatment duration and initial heparin therapy ensured enrollment of a broad range of eligible patients—including those with more severe disease1

  • ~60% of patients had deep vein thrombosis (DVT) (~40% of whom had extensive DVT [proximal with a clot involving the common femoral or iliac vein])1
  • ~40% had PE with or without DVT (~1/3 of whom also had right ventricular dysfunction [examined by computed tomography (CT) and N-terminal pro-brain natriuretic peptide [NT-proBNP] levels (500 pg/mL)]1

Consistent results across doses and subgroups4

In the Hokusai-VTE trial:

  • Efficacy results in major subpopulations, including patients with varying severities or other factors that increase bleeding risk, were consistent with the overall study population4
  • Bleeding results in major subpopulations, including patients with factors that increase bleeding risk,* were consistent with the overall study population4
  • *

    One or more of the following factors: moderate renal impairment (creatinine clearance [CrCl] of 30-50 mL/min), low body weight (≤60 kg/132 lbs), concomitant use of P-glycoprotein (P-gp) inhibitors (eg, cyclosporine, dronedarone, ketoconazole, erythromycin).6

  • §

    Major bleeding in nonsurgical patients was defined as4

    1. Fatal bleeding, and/or
    2. Symptomatic bleeding in critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, or intramuscular with compartment syndrome, and/or
    3. Bleeding causing a fall in haemoglobin level of 20 g/L-1 (1.24 mml/L-1) or more, or leading to transfusing of 2 or more units of whole blood or red cells.
  • §

    Clinically relevant nonmajor bleeding was defined as overt bleeding not meeting the criteria for major bleeding* but associated with medical intervention, unscheduled contact (visit or telephone call) with a physician, (temporary) cessation of study treatment, or associated with any other discomfort such as pain, or impairment of activities of daily life.1