Fondaparinux clinical trials

Fondaparinux, the factor Xa-binding pentasaccharide (Arixtra, MW 1,728 Da), is prepared synthetically, unlike UFH, LMWH and danaparoid, which are obtained from animal sources. Despite only inactivating free factor Xa, clinical trials indicate that fondaparinux is an effective antithrombotic agent, both for venous thromboembolism prophylaxis and treatment, as well as for acute coronary syndrome and ST elevation myocardial infarction [4]. 

Thrombocytopenia Moderate thrombocytopenia (platelet counts between 100,000/mm and 50,000/mm ) occurred at a rate of 2.9% in patients in orthopedic clinical trials. Severe thrombocytopenia (platelet counts less than 50,000/mm ) occurred at a rate of 0.2% in patients in orthopedic clinical trials. Moderate thrombocytopenia occurred at a rate of 0.5% in patients given the fondaparinux treatment regimen in the DVT and PE treatment clinical trials. Severe thrombocytopenia occurred at a rate of 0.04% in patients given the fondaparinux treatment regimen in the DVT and PE treatment clinical trials. 

Fondaparinux is a chemically synthesized pentasaccharide that mimics the antithrombin-binding site of heparin and LMWH. Its molecular size (1728Da) is too small to bind to thrombin molecules while it is bound to antithrombin, Therefore, it is a pure anti-Xa inhibitor. It binds very little to platelets, proteins, or endothelium and is excreted in the urine, It does not form a complex with PF4 or other positively charged molecules. It is not neutralizable by protamine sulfate, Recent clinical trials have resulted in FDA approval for prophylaxis of deep vein thrombosis in orthopedic surgery, It has been shown to be effective and safe for the treatment of pulmonary embolism (20,21) and ACS (non-ST-elevation Ml) (OASIS 5—Michelangelo Trial) (17). 

Idraparinux is an analog of fondaparinux that has a very long duration of effect (see Table 19-6) and has been developed to be administered once weekly by subcutaneous injection." Idraparinux is currently undergoing phase III clinical trials evaluating its utility for both the acute and long-term management of VTE." ... 

In a series of large, well-designed phase III clinical trials, fondaparinux was superior to enoxaparin for the prevention of VTE in patients undergoing lower extremity orthopedic surgery. However, the rate of symptomatic PE and death was... 

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