Thrive I: Efficacy and Tolerability of the Novel, Oral Direct Thrombin Inhibitor Ximelagatran Compared with Standard Therapy for the Treatment of Acute Deep Venous Thrombosis

Reviewer: Walter F. Sall, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: December 10, 2001

Presenter: Sam Schulman
Presenter's Affiliation: Karolinska Hospital, Stockholm, Sweden
Type of Session: Scientific

Background

Ximelagatran is an orally available, direct thrombin inhibitor. It is absorbed and converted to its active form, melagatran. It has a rapid onset, reaching peak serum concentration after 2-3 hours and does not require dose titration or routine coagulation monitoring. No drug or food interactions are known.

The objective of this study was to determine the safety, efficacy and optimal dosing for this drug in comparison to standard dalteparin followed by coumadin for patients with documented DVT.

Materials and Methods

This was a randomized, controlled, dose-blinded study from 41 centers in Europe. Four dose levels of Ximelegatran (from 24 to 60 mg twice daily) vs. Dalteparin (20 mg/kg) plus warfarin were tested.

Outcome measures included change in thrombus size and Marder score as assessed by venography on the day of randomization and on day 14. Symptomatic progression was also assessed.

350 patients were evaluated. 4% of patients had cancer.

Up to 24 hours of treatment with conventional anti-coagulation was allowed prior to randomization.

Results

69% of patients had regression of thrombus. The change was similar among all dose levels and the dalteparin group.

No difference in the change in Marder Score was seen in any of the groups.

A similar improvement in pain symptoms was seen in all groups.

The PE rate was 1-2% in all groups. 1-2% discontinued therapy due to bleeding complications in all groups.

Author's Conclusions

Ximelegatran is a well tolerated and efficacious alternative to standard dalteparin/coumadin in the treatment of DVT.

Routine monitoring of seum drug levels or coagulation is not necessary.

Initial parenteral treatment with heparin or low molecular weight heparin is unneccessary.

Comparable effect of different dose levels of the drug suggest a wide range of therapeutic efficacy

Clinical/Scientific Implications
Oral ximelegatran appears to be a satisfactory alternative to conventional parenteral anticoagulant therapy in the initial treatment of DVT. Its oral formulation promises to improve patient compliance and simplify treatment.

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