Results of Major International VTE Prevention Phase III Program Show Superior Benefits of the Pentasaccharide Org31540/SR90107APARIS, Dec. 5, 2000--The results of the four Phase III international clinical trials on the pentasaccharide Org31540/SR90107A, were presented yesterday at the 42nd annual meeting of the American Society of Hematology in San Francisco. These results, which were the subject of a press release from McMaster University, Ontario, Canada, are outlined below.
The results of the international Phase III program on the pentasaccharide Org31540/SR90107A show that Org31540/SR90107A provides a superior benefit over a low molecular weight heparin (reference treatment) in major orthopedic surgery patients, with an overall relative risk reduction of 50% and a similar safety profile.
Phase III of the world-wide venous-thromboembolism (VTE) prevention program was carried out on more than 7,000 patients undergoing major orthopedic surgery and constitutes the largest, most comprehensive development program ever conducted in this patient population.
The program consisted of four multicenter, prospective, double blind, randomized Phase III trials all of which compared Org31540/SR90107A with the reference treatment in the prevention of VTE:
- EPHESUS: following elective hip replacement surgery;
- PENTATHLON 2000: following elective hip replacement surgery;
- PENTHIFRA: following hip fracture surgery;
- PENTAMAKS: following elective major knee surgery.
A major improvement in the efficacy of VTE prophylaxis following major orthopedic surgery
Patients undergoing major orthopedic surgery are at high risk of venous thromboembolic events. Prophylaxis is thus required to prevent deep-vein thrombosis (DVT) and pulmonary embolism (PE). Despite the prevention provided by current therapies, there are still unmet medical needs in terms of efficacy.
The clinical data generated by the four studies show that the new compound Org31540/SR90107A provides a major improvement in terms of efficacy in the prevention of VTE following orthopedic surgery. Versus the reference treatment, Org31540/SR90107A reduced incidence of both total and proximal DVT by 50%.
In the four studies constituting the Phase III program, the same dose regimen of Org31540/SR90107A (2.5mg once daily started post-operatively) was compared to the standard, approved regimens of the reference treatment. The benefit of Org31540/SR90107A was consistent whatever the type of surgery, the type of anesthesia and the regimens of the reference treatment, and regardless of patients' gender, age and weight. The benefit of Org31540/SR90107A was also consistent whatever the location of deep-vein thrombosis (DVT), i.e. proximal, distal or both.
Org31540/SR90107A is thus the first antithrombotic agent to demonstrate a significant benefit over the reference treatment for the prevention of VTE in all three types of orthopedic surgery: hip fracture, hip replacement and knee surgery.
A well tolerated antithrombotic agent
The safety profile of Org31540/SR90107A is similar to that of the reference treatment. Mortality rates for any cause (15 deaths with Org31540/SR90107A and 21 deaths with the reference treatment at day 11) were similar in the two groups.
Bleeding rates within the two groups were also similar for the most clinically relevant bleeding criteria: fatal bleeding (no fatal bleeding with Org31540/SR90107A; one with the reference treatment); bleeding in critical organs (no non-fatal bleeding with Org31540/SR90107A; one with the reference treatment); and bleeding leading to intervention (0.33% for Org31540/SR90107A and 0.25% for the reference treatment).
Patients requiring a transfusion of more than or equal to 2 units and/or with a decrease of hemoglobin greater than or equal to 2g/dl, represented 2.3% of patients in the Org31540/SR90107A group and 1.4% of patients in the reference treatment group.
Total incidence of other bleedings (minor) was similar in the two groups (3.0% in Org31540/SR90107A group and 2.7% in the reference treatment group).
Org31540/SR90107A is the first agent of a new class of antithrombotics: selective factor Xa inhibitors. An original, entirely synthetic compound, Org31540/SR90107A was discovered and is being co-developed by Sanofi-Synthélabo and Organon in the prophylaxis and treatment of venous and arterial thrombo-embolic diseases.
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Posted: June 2004