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A dose-ranging study evaluating once-daily oral administration of the factor Xa inhibitor rivaroxaban in the treatment of patients with acute symptomatic deep vein thrombosis: the Einstein–DVT Dose-Ranging Study

Harry R. Buller, Anthonie W. A. Lensing, Martin H. Prins, Giancarlo Agnelli, Alexander Cohen, Alexander S. Gallus, Frank Misselwitz, Gary Raskob, Sebastian Schellong and Annelise Segers

Data supplements

Article Figures & Data

Figures

  • Figure 1

    Patient disposition. Chart of patients by randomized regimen. * indicates baseline or end-of-treatment CUS/PLS not done or not evaluable or not in time window. # indicates CUS/PLS performed more than 10 days after cessation of study medication, insufficient compliance, not allowed comedication. § indicates less than 4 days of LMWH, insufficient INR control, or CUS/PLS performed more than 10 days after cessation of study medication.

Tables

  • Table 1

    Baseline characteristics and treatment details of the safety population

    Patient characteristicRivaroxabanLWMH/VKA n = 137
    20 mg, n = 13530 mg, n = 13440 mg, n = 136
    Male sex, n (%)64 (47)69 (51)71 (52)73 (53)
    Age, y (range)*58 (22-87)57 (18-89)60 (22-94)57 (21-92)
    Weight, kg (range)80 (45-140)81 (40-140)81 (37-154)79 (41-134)
    BMI, kg/m2 (range)28 (16-47)27 (18-53)28 (15-45)27 (18-39)
    Active cancer, n (%)11 (8)14 (10)16 (12)10 (7)
    Previous DVT or PE, n (%)28 (21)25 (19)31 (23)40 (29)
    Recent surgery or trauma, n (%)26 (19)36 (27)30 (22)33 (24)
    Recent immobilization for >3 days, n (%)18 (13)20 (15)21 (15)18 (13)
    Most proximal DVT location, n (%)
        Trifurcation8 (6)6 (4)6 (4)4 (3)
        Popliteal vein48 (37)46 (35)44 (33)49 (37)
        Superficial femoral vein31 (24)38 (29)38 (29)32 (24)
        Common femoral vein44 (34)42 (32)45 (34)49 (37)
    Perfusion defect at baseline, n (%)90 (67)103 (77)91 (67)89 (65)
    Rivaroxaban trough levels at day 43, median (IQR) ng/mL32 (19-60)47 (24-83)50 (31-96)
    Rivaroxaban peak levels at day 84, median (IQR) ng/mL244 (175-360)293 (184-399)365 (205-564)
    Premature discontinuation, n (%)17 (13)19 (14)12 (9)15 (11)
        Adverse event, n (%)9 (7)7 (5)5 (4)5 (4)
        Consent withdrawn, n (%)2 (1)2 (1)2 (1)3 (2)
        Other, n (%)6 (4)10 (7)5 (4)7 (5)
    • BMI indicates body mass index; IQR, interquartile range; and —, not applicable.

  • Table 2

    Efficacy outcomes in the per-protocol population, n = 449

    RivaroxabanLMWH/VKA n = 101
    20 mg, n = 11530 mg, n = 11240 mg, n = 121
    Primary efficacy outcome
        n (%)7 (6.1)6 (5.4)8 (6.6)10 (9.9)
        95% CI*2.5%-12.1%2.0%-11.3%2.9%-12.6%4.9-17.5%
    Symptomatic events, n (%)3 (2.6)4 (3.6)2 (1.7)7 (6.9)
        Death (VTE-related)0 (0.0)2 (1.8)1 (0.8)0 (0.0)
        PE, nonfatal1 (0.9)1 (0.9)0 (0.0)1 (1.0)
        Recurrent DVT2 (1.7)1 (0.9)1 (0.8)7 (6.9)
    Asymptomatic deterioration on ultrasound and/or perfusion lung scanning, n (%)4 (3.5)2 (1.8)6 (5.0)3 (3.0)
    • CI indicates confidence interval; DVT, deep vein thrombosis; PE, pulmonary embolism; and VTE, venous thromboembolism.

    • * Two-sided 95% confidence intervals are presented.

    • One patient presented with both DVT and PE.

  • Table 3

    Safety outcomes in the safety population, n = 542

    RivaroxabanLMWM/VKA n = 137
    20 mg, n = 13530 mg, n = 13440 mg, n = 136
    Principal safety outcome, n (%)8 (5.9)8 (6.0)3 (2.2)12 (8.8)
        5% CI*2.6%-11.3%2.6%-11.4%0.5%-6.3%4.6%-14.8%
        Major bleeding, n (%)1 (0.7)2 (1.5)0 (0.0)2 (1.5)
        Clinically relevant, nonmajor bleeding, n (%)7 (5.2)6 (4.5)3 (2.2)10 (7.3)
    Any bleeding, n (%)31 (23.0)29 (21.6)29 (21.3)38 (27.7)
    Death (any cause), n (%)4 (3.0)8 (6.0)2 (1.5)5 (3.6)
        PE0 (0)0 (0)0 (0)0 (0)
        Unexplained, PE not excluded0 (0)2 (1.5)1 (0.7)0 (0)
        Bleeding0 (0)0 (0)0 (0)1 (0.7)
        Malignancy3 (2.2)4 (3.0)1 (0.7)3 (2.2)
        Other1 (0.7)2 (1.5)0 (0)1 (0.7)