Dabigatran Etexilate in Extended Venous Thromboembolism (VTE) Prevention After Hip Replacement Surgery

• Major Venous Thromboembolic Event and Venous Thromboembolic Event-related Mortality During Treatment Period [ Time Frame: 28 - 35 days ] [ Designated as safety issue: Yes ]
  Major Venous Thromboembolic Event (VTE) is defined as proximal DVT and PE, as adjudicated by the VTE events committee
• Proximal Deep Vein Thrombosis During Treatment Period [ Time Frame: 28 - 35 days ] [ Designated as safety issue: Yes ]
  Proximal Deep Vein Thrombosis as adjudicated by the VTE events committee
• Total Deep Vein Thrombosis During Treatment Period [ Time Frame: 28 - 35 days ] [ Designated as safety issue: Yes ]
  Total Deep Vein Thrombosis as adjudicated by the VTE events committee
• Symptomatic Deep Vein Thrombosis During Treatment Period [ Time Frame: 28 - 35 days ] [ Designated as safety issue: Yes ]
  Symptomatic Deep Vein Thrombosis, confirmed by venous duplex, ultrasound, venography or autopsy, and as adjudicated by the VTE events committee
• Pulmonary Embolism During Treatment Period [ Time Frame: 28 - 35 days ] [ Designated as safety issue: Yes ]
  Pulmonary embolism confirmed by pulmonary V-Q scintagraphy, chest x-ray, pulmonary angiography, spiral CT or autopsy, and as adjudicated by the VTE events committee
• Death During Treatment Period [ Time Frame: 28 - 35 days ] [ Designated as safety issue: Yes ]
  All cause death, as adjudicated by the VTE events committee
• Total Venous Thromboembolic Event (VTE) and All-cause Mortality During the Follow-up Period [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  Total Venous Thromboembolic Event (VTE) includes both proximal and distal deep vein thrombosis (DVT) (detected by routine venography), symptomatic DVT (confirmed by venous duplex, ultrasound, venography or autopsy) and pulmonary embolism (PE) (confirmed by pulmonary V-Q scintagraphy, chest x-ray, pulmonary angiography, spiral CT or autopsy).
• Major Bleeding Events During Treatment Period [ Time Frame: 28 - 35 days ] [ Designated as safety issue: Yes ]

  Major bleeding events were defined according to the modified McMaster criteria, and were adjudicated by a bleed adjudication committee. The bleeding event had to fulfil at least one of the following criteria in order to be classified as major:-

  • fatal
  • clinically overt associated with loss of haemoglobin >=20g/L in excess of what was expected
  • clinically overt leading to the transfusion of >=2 units packed cells or whole blood in excess of what was expected
  • symptomatic retroperitoneal, intracranial, intraocular or intraspinal
  • requiring treatment cessation
  • leading to re-operation

The objective of this study is to determine the comparative efficacy and safety of two oral regimens of dabigatran etexilate, compared to a standard subcutaneous regimen of enoxaparin, in prevention of venous thromboembolism in patients with primary elective total hip replacement surgery.

• Thromboembolism
• Arthroplasty, Replacement, Hip

• Drug: dabigatran etexilate
  daily dose 150 mg once daily, half a dose on the day of surgery
• Drug: enoxaparin
  40 mg once daily

• Experimental: dabigatran etexilate 75 mg
  daily dose 150 mg once daily, half a dose on the day of surgery
  Intervention: Drug: dabigatran etexilate
• Experimental: dabigatran etexilate 110 mg
  daily dose 220 mg once daily, half a dose on the day of surgery
  Intervention: Drug: dabigatran etexilate
• Active Comparator: enoxaparin
  40 mg once daily
  Intervention: Drug: enoxaparin

Inclusion criteria

Inclusion criteria (selected):

• Patients (18 years or older) scheduled to undergo a primary, unilateral, elective total hip replacement
• Written Informed Consent

Exclusion criteria

Exclusion criteria (selected):

• Patients with an excessive risk of bleeding, for example because of history of bleeding diathesis major surgery or trauma within the last 3 months history of haemorrhagic stroke or any of the following intracranial pathologies: bleeding, neoplasm, AV malformation or aneurysm clinically relevant bleeding or gastric / duodenal ulcer within the last 6 months treatment with anticoagulants within 7 days prior to joint replacement surgery or anticipated need during the study treatment period thrombocytopenia.
• Active malignant disease or current cytostatic treatment
• Known severe renal insufficiency
• Liver disease expected to have any potential impact on survival, or elevated AST or ALT > 2x upper limit of normal
• Recent unstable cardiovascular disease or history of myocardial infarction within the last 3 months
• Pre-menopausal women who are pregnant or nursing, or are of child-bearing potential and are not practising or do not plan to continue practising acceptable methods of birth control
• Allergy to radio opaque contrast media or iodine, heparins (incl. heparin induced thrombocytopenia) or dabigatran
• Contraindications to enoxaparin
• Participation in a clinical trial during the last 30 days