Dabigatran Etexilate Compared With Enoxaparin in Prevention of Venous Thromboembolism (VTE) Following Total Hip Arthroplasty
Condition: Venous Thromboembolism
MeSH terms: Thromboembolism; Venous Thromboembolism
Intervention: Enoxaparin; Dabigatran etexilate
Intervention description: 40 mg once daily; 220 mg once daily
Intervention MeSH terms: Enoxaparin; Dabigatran
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 2055.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of the trial is to demonstrate non-inferiority of 220 mg oral
      dabigatran etexilate compared to 40 mg subcutaneous enoxaparin administered once daily.
      Safety and efficacy will be compared between the treatment groups.
    

Eligibility criteria:

        Inclusion criteria:

          -  Patients scheduled to undergo primary, unilateral, elective total hip arthroplasty.

          -  Male or female 18 years of age or older.

          -  Patients giving written informed consent for study participation.

        Exclusion criteria:

          -  Patients weighing less than 40 kg.

          -  History of bleeding diathesis.

          -  Patients who in the investigators judgement are perceived as having an excessive risk
             of bleeding, for example, constitutional or acquired coagulation disorders or because
             of anticipated need of quinidine, verapamil or other restricted medication during the
             treatment period (see Section 4.2.2).

          -  Major surgery or trauma (e.g., hip fracture) within 3 months of enrolment.

          -  Recent unstable cardiovascular disease (in the investigators opinion) such as
             uncontrolled hypertension, that is ongoing at the time of enrolment or history of
             myocardial infarction within 3 months of enrolment.

          -  Any history of haemorrhagic stroke or any of the following intracranial pathologies:
             bleeding, neoplasm, Atriovenous (AV) malformation or aneurysm.

          -  Ongoing treatment for Venous Thromboembolism (VTE).

          -  Clinically relevant bleeding (gastrointestinal, pulmonary, intraocular or urogenital
             bleeding) within 6 months of enrolment.

          -  Gastric or duodenal ulcer within one year of enrolment.

          -  Liver disease expected to have any potential impact on survival (ie, hepatitis B or C,
             cirrhosis). This does not include Gilberts syndrome or hepatitis A with complete
             recovery.

          -  Active liver disease or liver disease decreasing survival (e.g, acute hepatitis,
             chronic active hepatitis, cirrhosis) or Alanine Aminotransferase (ALT) >3 x ULN.

          -  Known severe renal insufficiency (CrCl <30 ml/min). Note: CrCl should be calculated
             only if serum creatinine is elevated or renal insufficiency is suspected. See Appendix
             10.1 for calculation.

          -  Elevated creatinine that, in the investigators opinion, contraindicates venography.

          -  Treatment with anticoagulants, clopidogrel, ticlopidine, abciximab, aspirin >162.5
             mg/day or NSAID with t 1/2 >12 hours within 7 days prior to hip replacement surgery OR
             anticipated need while the patient is receiving study medication and prior to 24 hours
             after the last administration of any blinded study medication (COX-2 selective
             inhibitors are allowed).

          -  Anticipated required use of intermittent pneumatic compression and electric
             stimulation of lower limb.

          -  Pre-menopausal women (last menstruation within 1 year prior to signing informed
             consent) who:

               -  Are pregnant.

               -  Are nursing.

               -  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 intrauterine device; oral,
                  implantable or injectable contraceptives and surgical sterility.

          -  Known allergy to radio opaque contrast media.

          -  History of thrombocytopenia, including heparin-induced thrombocytopenia, or a platelet
             count <100,000 cells/microliter at randomisation.

          -  Allergy to heparins or dabigatran etexilate.

          -  Active malignant disease or current cytostatic treatment. Patients should be disease
             free for at least 5 years.

          -  Participation in a clinical trial within 30 days of randomisation.

          -  Leg amputee.

          -  Known alcohol or drug abuse which would interfere with completion of the study.

          -  Contraindications to enoxaparin.

          -  Previous participation in this study.