Prevention of venous thromboembolism in patients with primary elective total knee replacement
Conditions
Interventions
Product Name: dabigatran etexilate
Product Code: BIBR 1048 MS
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: dabigatran etexilate
Sponsors
Boehringer Ingelheim Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients scheduled to undergo a primary, unilateral elective total knee replacement 2. Male or female 18 years of age or older 3. Patients weighing at least 40 kg 4. Written informed consent prior to the start of study participation. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. History of bleeding diathesis 2. Constitutional or acquired coagulation disorders that in the investigator’s judgment puts the patient at excessive risk for bleeding 3. Major surgery or trauma (e.g. hip fracture) within the last 3 months 4. Recent unstable cardiovascular disease, such as uncontrolled hypertension at the time of enrollment (investigator’s judgment) or history of myocardial infarction within the last 3 months 5. Spinal or epidural anesthesia, for which more than 3 attempts (sticks) at placement were made, or the placement was traumatic. Please note that patients, who are not excluded under this criterion, are to have the catheter pulled at the completion of surgery. 6. Any history of hemorrhagic stroke or any of the following intracranial pathologies: bleeding, neoplasm, AV malformation or aneurysm 7. History of VTE still requiring specific treatment 8. Clinically relevant bleeding (e.g. gastrointestinal, pulmonary, intraocular or urogenital bleeding) within the last 6 months 9. Gastric or duodenal ulcer within the last year 10. Liver disease expected to have any potential impact on survival (e.g. hepatitis B or C, cirrhosis, but not Gilbert’s syndrome or hepatitis A with complete recovery) 11. Elevated AST or ALT >2x upper limit of normal, based on central lab results or local lab results within 1 month before enrollment 12. Known severe renal insufficiency (CrCl 160 mg/day or NSAID with t½ > 12 hours within 7 days prior to knee replacement surgery or anticipated need during the study treatment period (COX-2 selective inhibitors are allowed) 15. Anticipated required use of intermittent pneumatic compression and electric stimulation of lower limb 16. Pre-menopausal women (last menstruation ?1 year prior to signing informed consent) who: a) are pregnant b) are nursing c) are of child-bearing potential and are NOT practicing acceptable methods of birth control, or do NOT plan to continue practicing an acceptable method throughout the study. Acceptable methods of birth control include Intra Uterine Device (IUD), oral, implantable, patch or injectable contraceptives and surgical sterility. 17. Known allergy to radio opaque contrast media 18. History of thrombocytopenia (including heparin induced thrombocytopenia) or a platelet count < 100,000 cells/microliter at visit 1 19. Allergy to heparins or dabigatran 20. Active malignant disease or current cytostatic treatment 21. Participation in a clinical trial during the last 30 days 22. Leg amputee 23. Known alcohol or drug abuse which would interfere with completion of the study 24. Contraindications to enoxaparin 25. Previous participation in this st
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The goal of this study is to determine the comparative efficacy and safety of two different dose regimens (75mg day 1 followed by 150 mg day 2 to completion, and 110 mg day 1 followed by 220 mg day 2 to completion) of dabigatran administered orally (capsules), compared to enoxaparin 30 mg twice a day subcutaneous, in prevention of venous thromboembolism in patients with primary elective total knee replacement surgery. ; Secondary Objective: Secondary efficacy endpoints will include any of the following that occur during the treatment period: 1. Composite of major VTE (defined as proximal DVT and PE) and VTE related mortality (endpoint recommended in the EMEA advice for non-inferiority therapeutic confirmatory trials (1)) 2. Proximal Deep-Vein Thrombosis (DVT) 3. Total DVT 4. Symptomatic DVT 5. Pulmonary Embolism (PE) 6. Death An additional secondary efficacy endpoint will be the composite of total VTE and all-cause mortality during the follow-up period. ; Primary end point(s): The primary efficacy endpoint of this study is the composite of total venous thromboembolic events (VTE) and all-cause mortality. Total VTE includes: - deep vein thrombosis (proximal and distal) as detected by routine bilateral venography performed within 24 hours after the last oral study medication - symptomatic DVT occurring during the treatment period, confirmed by venography, venous duplex ultrasound or by autopsy - pulmonary embolism confirmed by perfusion (Q) scintigraphy and chest X-ray or pulmonary angiography or spiral CT | — |
Countries
United Kingdom
Outcome results
None listed