An Oral, Direct Factor Xa Inhibitor, BAY59-7939, for Prophylaxis Against Venous Thromboembolism After Total Knee Replacement: a Dose-Ranging Study

This study has been completed.
Sponsor:
Information provided by:
Bayer
ClinicalTrials.gov Identifier:
NCT00402467
First received: November 21, 2006
Last updated: April 19, 2010
Last verified: April 2010
  Purpose

The study drug, BAY59-7939, is a new drug currently being tested in the prevention of VTE. It directly inhibits factor Xa, a blood component in the pathway which leads to coagulation (clotting of blood cells). It is available as a tablet. The purpose of this study is to compare the safety and efficacy of BAY59-7939 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. In this study 4 different doses of the investigational drug BAY59-7939 will be tested in comparison to Enoxaparin. You will receive during the study either one of the following BAY59-7939 treatments or Enoxaparin. The following doses of BAY59-7939 will be tested: Dose I ; Dose II, Dose III, Dose IV. This study will run for approximately 7 months in a number of countries. In total, up to 600 patients may participate in this study.


Condition Intervention Phase
Venous Thromboembolism
Drug: Rivaroxaban (BAY59-7939)
Drug: Rivaroxaban, (BAY59-7939)
Drug: Enoxaparine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Prevention

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Composite endpoints of Deep vein Thrombosis (proximal and/or distal),non fatal PE and death from all causes [ Time Frame: 5-9 days after surgery or earlier in case of symptoms indicating deep vein Thrombosis. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of DVTs (total, proximal, distal) [ Time Frame: Day 6-10 ] [ Designated as safety issue: Yes ]
  • Incidence of symptomatic VTEs [ Time Frame: Day 6-10 ] [ Designated as safety issue: Yes ]
  • The composite endpoint that results from the primary endpoint by substituting VTE related death for all deaths [ Time Frame: Day 6-10 ] [ Designated as safety issue: Yes ]
  • Incidence of symptomatic VTEs (total, PE, DVT) [ Time Frame: Day 6-10 ] [ Designated as safety issue: Yes ]

Enrollment: 600
Study Completion Date: November 2004
Arms Assigned Interventions
Experimental: Arm 6 Drug: Enoxaparine
30mg bid
Experimental: Arm 1 Drug: Rivaroxaban (BAY59-7939)
2.5mg bid
Experimental: Arm 2 Drug: Rivaroxaban, (BAY59-7939)
5mg bid
Experimental: Arm 3 Drug: Rivaroxaban, (BAY59-7939)
10 mg bid
Experimental: Arm 4 Drug: Rivaroxaban, (BAY59-7939)
20mg bid
Experimental: Arm 5 Drug: Enoxaparine
30mg bid

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male subjects aged 18 years or above and postmenopausal female subjects
  • Subjects scheduled for elective total knee replacement
  • Subjects written informed consent for participation after receiving detailed written and oral information previous to any study specific procedures

Exclusion Criteria:

Related to medical history:

  • Any prior DVT or PE
  • Myocardial infarction (MI), TIA or ischaemic stroke within the last 6 months prior to randomization
  • History of heparin-induced thrombocytopenia, allergy to heparins
  • Intracerebral or intraocular bleeding within the last 6 months prior to randomization
  • History of gastrointestinal disease (e.g. active peptic ulcer) with gastrointestinal bleeding within the last 6 months prior to randomization
  • History or presence of gastrointestinal disease which could result in an impaired absorption of the study drug (e.g. severe active inflammatory bowel disease, short gut syndrome)
  • 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)including patients with acquired or congenital thrombophilia
  • Thrombocytopenia (platelets < 100,000/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 or decreased creatinine clearance < 30ml/min)
  • 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:

  • Therapy with oral anticoagulants (e.g. phenprocoumon, warfarin-sodium, heparins and factor Xa inhibitors other than study medication) and fibrinolytic therapy
  • Therapy with acetylic salicylic acid or other thrombocyte aggregation inhibitors (e.g. clopidogrel, dipyridamole and ticlopidine) should be stopped one week before enrollment. Patient not able to stop ASA therapy will be excluded
  • All other drugs influencing coagulation, (exception: NSAIDs with half life < 17 hrs will be allowed)
  • Systemic and topical treatment with azole compounds (e.g. ketoconazole, fluconazole, itraconazole). Azole compounds should be stopped at least four days before enrollment

Miscellaneous:

  • Planned intermittent pneumatic compression during active treatment period
  • Planned epidural anaesthesia with indwelling epidural catheter (spinal and epidural anaesthesia without indwelling catheter is allowed)
  • Therapy with another investigational product within 30 days prior to the start of the study
  • Concomitant participation in another trial or study

Removal of Subjects from Study:

A subject who withdraws is one who discontinued a clinical study for any reason.

Subjects may be withdrawn from the study for the following reasons:

  • At their own request or at the request of their legally acceptable representative
  • If, in the investigator's opinion, continuation in the study would be detrimental to the subject's well-being
  • At the specific request of the sponsor
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00402467

  Show 36 Study Locations
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Therapeutic Area Head, Bayer Healthcare Pharmaceutical Inc.
ClinicalTrials.gov Identifier: NCT00402467     History of Changes
Other Study ID Numbers: 10945
Study First Received: November 21, 2006
Last Updated: April 19, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Bayer:
Prevention of venous thromboembolism

Additional relevant MeSH terms:
Venous Thromboembolism
Venous Thrombosis
Thromboembolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Thrombosis
Rivaroxaban
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014