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Patients undergoing surgery, especially hip and knee surgery, are at high risk for VTE (up to 60 % without prophylaxis). The administration of drugs for thromboprophylaxis, such as heparins, significantly lowers that risk, but heparins have to be applied below the skin (subcutaneously). Additionally, there is a chance of developing a heparin-induced thrombocytopenia (decrease in platelets). Therefore, there is still a need for new agents which are safer and more efficient and which are easier to apply.The purpose of this study is to compare the safety and efficacy of BAY 59-7939 with the safety and efficacy of the licensed drug Enoxaparin. Enoxaparin, a so-called low molecular heparin, is approved and widely used in the area of thromboprophylaxis and will be given once daily subcutaneously.Another important purpose of the study is to find the optimal dose of BAY 59-7939 for thromboprophylaxis after hip replacement surgery. Therefore, there are several dose steps planned.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 2 | Active Comparator |
| |
| Arm 1 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rivaroxaban (BAY59-7939) | Drug | 2,5 mg bid,5 mg bid,10mg bid, 20 mg bid, 20 mg tid, 30 mg bid, dose escalation trial |
|
| Measure | Description | Time Frame |
|---|---|---|
| The primary efficacy endpoint is a composite endpoint of: - Any DVT (proximal and/or distal) and - Non fatal PE and - Death from all causes. The primary endpoint will be evaluated 5 - 9 days after surgery. | Assymptomatic DVT will be measured 5-9 days after surgery Symptomatc DVT , non-fatal PE and Death from all causes will be measured 41 days after surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of DVTs (total, proximal, distal) | will be evaluated 5 - 9 days after surgery. | |
| Incidence of symptomatic VTEs | 41 days after surgery | |
| The composite endpoint that results from the primary endpoint by using alternative definition of deaths (i.e. VTE related death) |
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Inclusion Criteria:
Exclusion Criteria:
DVT or PE within the previous 6 months prior to study entry.
Myocardial infarction (MI) or cerebrovascular attack (CVA), TIA or ischaemic stroke within the last 6 months prior to study entry.
History of heparin-induced thrombocytopenia, allergy to heparins.
Intracerebral or intraocular bleeding within the last 6 months prior to study entry.
History of gastrointestinal disease with gastrointestinal bleeding within the last 6 months prior to the study.
History or presence of gastrointestinal disease which could result in an impaired absorption of the study drug
Amputation of one leg.Related to current symptoms or findings
Heart insufficiency NYHA III-IV.
Congenital or acquired haemorrhagic diathesis (PT INR/aPTT not within normal limits).
Thrombocytopenia (platelets < 50.000/µl).
Macroscopic haematuria.
Allergy to contrast media.
Severe hypertension (SBP > 200mmHg, DBP > 100 mmHg).
Impaired liver function (transaminases > 2 x ULN).
Impaired renal function (serum creatinine > 1.5 x ULN).
Active malignant disease.
Presence of active peptic ulcer or gastrointestinal disease with increased risk of gastrointestinal bleeding.
Body weight < 45 kg.
Drug- or alcohol abuse.
Related to current treatment
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| Name | Affiliation | Role |
|---|---|---|
| Bayer Study Director | Bayer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Wiener Neustadt | Lower Austria | 2700 | Austria | |||
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| Enoxaparin | Drug | 40 mg bid |
|
| 41 days after surgery |
| Incidence of symptomatic VTEs (total, PE, DVT) within 30 days after stop of treatment with the study drug. | 41 days after surgery |
| Vienna |
| State of Vienna |
| 1220 |
| Austria |
| Linz | Upper Austria | 4010 | Austria |
| Baudour | 7331 | Belgium |
| Brussels | 1090 | Belgium |
| Ghent | 9000 | Belgium |
| Huy | 4500 | Belgium |
| Hellerup | 2900 | Denmark |
| Herlev | 2730 | Denmark |
| Hørsholm | DK-2970 | Denmark |
| Silkeborg | 8600 | Denmark |
| Amiens | 80030 | France |
| Lille | 59037 | France |
| Nancy | 54037 | France |
| Rheinfelden | Baden-Wurttemberg | 79618 | Germany |
| Fürth | Bavaria | 90766 | Germany |
| Garmisch-Partenkirchen | Bavaria | 82467 | Germany |
| Frankfurt am Main | Hesse | 60528 | Germany |
| Frankfurt am Main | Hesse | 65929 | Germany |
| Dresden | Saxony | 01307 | Germany |
| Berlin | State of Berlin | 14165 | Germany |
| Haifa | Israel | 31096 | Israel |
| Tel Aviv | 64239 | Israel |
| Tel Litwinsky | 52621 | Israel |
| Ẕerifin | 70300 | Israel |
| Amersfoort | 3818 ES | Netherlands |
| Zwolle | 8025 AB | Netherlands |
| Notodden | NO-3675 | Norway |
| Oslo | 0440 | Norway |
| Rjukan | NO-3660 | Norway |
| Bialystok | 15-276 | Poland |
| Gdansk | 80-742 | Poland |
| Krakow | 31-826 | Poland |
| Lodz | 91-425 | Poland |
| Lublin | 20-090 | Poland |
| Lublin | 20-718 | Poland |
| Warsaw | 00-909 | Poland |
| Gothenburg | 416 85 | Sweden |
| Jönköping | 551 85 | Sweden |
| Kungälv | 442 83 | Sweden |
| London | Greater London | SE5 9RS | United Kingdom |
| ID | Term |
|---|---|
| D013923 | Thromboembolism |
| ID | Term |
|---|---|
| D016769 | Embolism and Thrombosis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000069552 | Rivaroxaban |
| D017984 | Enoxaparin |
| ID | Term |
|---|---|
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D009025 | Morpholines |
| D010078 | Oxazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006495 | Heparin, Low-Molecular-Weight |
| D006493 | Heparin |
| D006025 | Glycosaminoglycans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
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