Hokusai-VTE

A SYMPTOMATIC RECURRENT VENOUS THROMBOEMBOLISM TRIAL

Hokusai-VTE was the largest single comparative VTE trial to date with a NOAC1

The study design aimed to broaden the applicability of LIXIANA® in the real-world treatment of DVT and PE through:

  • Enrollment of a broad range of patients, including those with extensive disease
  • Use of heparin, as recommended by clinical guidelines
  • Dose adjustment of LIXIANA® at randomisation or during the study (50% reduction i.e. from 60 mg to 30 mg) for patients perceived to be at increased risk of bleeding due to LIXIANA® overexposure – to reflect clinical practice*
  • Flexible treatment duration (3, 6 or 12 months), based on evolving evidence or clinician discretion


Study design1

Dosing strategy

Hokusai-VTE prospectively allowed for dose reduction in patients with one or more clinical factors which put them at increased risk of bleeding on LIXIANA® both at randomisation and during the trial:*1

  • Renal impairment (CrCl 30 to 50 ml/min)
  • Low body weight (≤60 kg/132 lbs)
  • Concomitant use of P-gp inhibitors verapamil, dronedarone or quinidine††


Hokusai-VTE: Studied DVT and PE patients you may see in your practice

Hokusai-VTE studied a broad range of patients, with varying degrees of DVT and PE, including challenging subgroups.1

Study highlights

  •  *

    60 mg is the recommended dose for most patients (~82%, n=3,385). ~18% (n=733) of patients received a dose reduction at randomisation from 60 mg to 30 mg LIXIANA® if they had one or more of the following clinical factors:
    - Renal impairment (CrCl 30 to 50 ml/min)
    - Low body weight (≤60 kg/132 lbs)
    - Concomitant use of P-gp inhibitors verapamil, dronedarone or quinidineclass
    The SPC differs from the clinical trial. Hence, no dose adjustment is required for concomitant use of verapamil, amiodarone and quinidine. In patients taking LIXIANA® and the following P-gp inhibitors; dronedarone, erythromycin, ketoconazole or ciclosporin, the recommended dose is LIXIANA® 30 mg once daily.

  • **

    Twenty-five patients did not receive study drug, resulting in 4,118 patients included in the efficacy and safety analysis.

  • Twenty-seven patients did not receive study drug, resulting in 4,122 patients included in the efficacy and safety analysis.

  • ††

    The SPC differs from the clinical trial. Hence, no dose adjustment is required for concomitant use of verapamil, amiodarone and quinidine. In patients taking LIXIANA® and the following P-gp inhibitors; dronedarone, erythromycin, ketoconazole or ciclosporin, the recommended dose is LIXIANA® 30 mg once daily.

  • The primary safety endpoint of Hokusai-VTE was a composite of major and clinically relevant nonmajor bleeding, as defined by the International Society on Thrombosis and Haemostasis (ISTH). Major bleeding was defined as overt bleeding associated with a decrease in haemoglobin of 2.0 g/L or more, or requiring a transfusion of 2 or more units of blood, occurring in a critical site or contributing to death. 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 other discomfort such as pain, or impairment of activities daily life.4

References

  1. The Hokusai-VTE Investigators. NEJM 2013;369(15):1406–1415.
  2. Data on file, Daiichi Sankyo UK Limited, DOF-EDX-002, June 2015.
  3. Raskob G et al. J Thromb Haemost 2013;11(7):1287–1294.
  4. The van Gogh Investigators. NEJM 2007;357:1094–1104.