Treatment of Patients Undergoing Primary Unilateral Elective Total Knee or Hip Replacement With Dabigatran Etexilate
Condition: Arthroplasty, Replacement; Prevention of Venous Thromboembolism; Moderate Renal Impairment (CrCl 30-50 mL/Min)
MeSH terms: Renal Insufficiency; Thromboembolism; Venous Thromboembolism
Intervention: Dabigatran etexilate
Intervention description: once daily approved dose by EMEA and Health Canada
Intervention MeSH terms: Dabigatran
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 142.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      To supplement the current evidence of the effect of Pradaxa® (dabigatran etexilate) on
      coagulation parameters, including a calibrated thrombin time test, in patients with moderate
      renal impairment undergoing elective total hip- or knee-replacement surgery, this PK/PD study
      will be conducted.
    

Eligibility criteria:

        Inclusion criteria:

          1. Patients scheduled for primary unilateral elective total knee or hip replacement, male
             or female being 18 years or older

          2. Moderate renal impairment (CrCl 30-50 mL/min)

          3. Written informed consent

          4. Caucasian patients

        Exclusion criteria:

          1. Patients weighing less than 40 kg.

          2. Patients requiring chronic treatment with anticoagulants (e.g. vitamin K antagonists;
             e.g. patients with atrial fibrillation, patients with artificial heart valves, etc.).

          3. Patients who in the investigator's judgment were perceived as having an excessive risk
             of bleeding, for example:

             Constitutional or acquired coagulation disorders

             History of bleeding diathesis

             Clinically relevant bleeding (gastrointestinal, pulmonary, intraocular or urogenital
             bleeding) within 3 months of enrolment

             Major surgery or trauma (e.g. hip fracture) within 3 months of enrolment

             History of thrombocytopenia, including heparin-induced thrombocytopenia, or a platelet
             count <100 000 cells/microliter at randomization

             Any history of hemorrhagic stroke or any of the following intracranial pathologies:
             bleeding, neoplasm

             Any arteriovenous malformations, vascular aneurysms or major intraspinal or
             intracerebral vascular abnormalities

             Presence of malignant neoplasms at higher risk of bleeding

             Known or suspected oesophageal varices

             Symptomatic or endoscopically documented gastroduodenal ulcer disease in the previous
             30 days

             Treatment with anticoagulants, clopidogrel, ticlopidine, abciximab, aspirin >162.5
             mg/day or non-steroidal anti-inflammatory drug (NSAID) with t1/2>12 hours within 7
             days prior to hip or knee replacement surgery OR anticipated need while the patient
             was receiving study medication and prior to 24 hours after the last administration of
             study medication (COX-2 selective inhibitors are allowed) because of anticipated need
             of quinidine, verapamil or other restricted medication during the treatment period

          4. Recent unstable cardiovascular disease (in the investigator's opinion) such as
             uncontrolled hypertension, that was ongoing at the time of enrolment or history of
             myocardial infarction within 3 months of enrolment.

          5. Ongoing treatment for VTE.

          6. Liver disease expected to have any potential impact on survival (i.e. hepatitis B or
             C, cirrhosis) or ALT/AST >3x upper limit of normal range (ULN). This did not include
             Gilbert's syndrome or hepatitis A with complete recovery.

          7. Known severe renal insufficiency (CrCl <30 mL/min) and patients with mild renal
             insufficiency (CrCl >50 mL/min) or normal renal function.

          8. Planned anaesthesia with post-operative indwelling epidural catheters.

          9. Pre-menopausal women (last menstruation <=1 year prior to signing informed consent),
             who were:

             Pregnant

             Nursing

             Of child-bearing potential and were NOT practicing acceptable methods of birth
             control, or did NOT plan to continue practicing an acceptable method throughout the
             study. Acceptable methods of birth control included intrauterine device; oral,
             implantable or injectable contraceptives and surgical sterility

         10. Hypersensitivity to dabigatran etexilate or to any of excipients.

         11. Participation in a clinical trial within 30 days of enrolment.

         12. Known alcohol or drug abuse which would interfere with completion of the study;
             patients considered unreliable by the investigator concerning the requirements for
             follow-up during the study and/or compliance with study drug administration.

         13. Previous participation in this study.