AN EXPLORATORY TRIAL OF 2 DOSAGES OF A NOVEL SYNTHETIC THROMBIN INHIBITOR (NAPSAGATRAN, RO 46-6240) COMPARED WITH UNFRACTIONATED HEPARIN FOR TREATMENT OF PROXIMAL DEEP-VEIN THROMBOSIS - RESULTS OF THE EUROPEANMULTICENTER ADVENT TRIAL

One hundred and ten patients with acute proximal deep-vein thrombosis were randomized in a sequential dose-finding design, to receive contin uous intravenous infusion of napsagatran, a novel synthetic thrombin-i nhibitor, at a fixed dose of 5 mg/h (n = 37) or 9 mg/h (n = 26), or AP TT-adjusted unfractionated heparin (n = 47). Oral anticoagulants were started on the 2nd day and the study drug was discontinued from the 5t h treatment day, as soon as the International Normalized Ratio was abo ve 2. Control venogram (97 venogram pairs evaluable) after 5-8 days of treatment showed improvement in 3 napsagatran-treated patients (versu s none in heparin-treated patients) and worsening in 4 napsagatran-tre ated patients (versus 2 in heparin-treated patients). The venographic Marder's score did not change among the treatment groups. New lung sca n perfusion defects (99 scintigram pairs evaluable) occurred in 4 (11% ), 4 (21%), and 4 (10%) patients in the napsagatran (5 mg/h) group, in the napsagatran (9 mg/h) group, and in the heparin control group, res pectively. Then was no statistically significant difference in any of these endpoints between the 3 groups. No major bleeding was observed a nd the rare minor bleedings occurred at a similar rate in the three tr eatment groups. In conclusion, the ADVENT trial has shown data that su ggest comparable efficacy and safety of a synthetic, direct thrombin i nhibitor (napsagatran) and conventional heparin therapy for treatment of proximal DVT. These results suggest that synthetic direct thrombin inhibitors are a promising class of antithrombotic agents which deserv es further development in this field.