Dabigatran Etexilate vs Enoxaparin in Prevention of Venous Thromboembolism (VTE) Post Total Knee Replacement

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00152971
First received: September 8, 2005
Last updated: April 22, 2014
Last verified: April 2014
  Purpose

To determine the comparative efficacy and safety of two different doses (75mg day 1 followed by 150 mg day 2-completion, and 110 mg day 1 followed by 220 mg day 2-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


Condition Intervention Phase
Arthroplasty, Replacement, Knee
Thromboembolism
Drug: Dabigatran Dose 1 - day 2 to completion
Drug: Dabigatran Dose 1 - day 1
Drug: Dabigatran Dose 2 - day 2 to completion
Drug: Dabigatran Dose 2 - day 1
Drug: Enoxaparin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: A Phase III, Randomized, Parallel-group, Double-blind, Active Controlled Study to Investigate the Efficacy and Safety of Two Different Dose Regimens (75mg Day 1 Followed by 150 mg Day 2-completion, and 110 mg Day 1 Followed by 220 mg Day 2-completion) of Dabigatran Etexilate Administered Orally (Capsules), Compared to Enoxaparin 30 mg Twice a Day Subcutaneous for 12 - 15 Days in Prevention of Venous Thromboembolism in Patients With Primary Elective Total Knee Replacement Surgery

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Number of Participants With Total Venous Thromboembolic Event and All-cause Mortality During Treatment Period [ Time Frame: First administration until 12-15 days ] [ Designated as safety issue: No ]

    Total Venous Thromboembolic Event (VTE) includes both proximal and distal deep vein thrombosis (DVT) (detected by routine bilateral venography), symptomatic DVT (confirmed by venous compression ultrasound, venography or autopsy) and pulmonary embolism (PE) (confirmed by pulmonary V-Q scintigraphy, chest x-ray, pulmonary angiography, spiral CT or autopsy).

    All of these components and all deaths were centrally adjudicated by the VTE events committee, which was not aware of the treatment allocation of the patients.



Secondary Outcome Measures:
  • Number of Participants With Major Venous Thromboembolic Event and Venous Thromboembolic Event-related Mortality During Treatment Period [ Time Frame: First administration until 12-15 days ] [ Designated as safety issue: No ]
    Major Venous Thromboembolic Event (VTE) is defined as proximal DVT and PE, as adjudicated by the VTE events committee

  • Number of Participants With Proximal Deep Vein Thrombosis During Treatment Period [ Time Frame: First administration until 12-15 days ] [ Designated as safety issue: No ]
    Proximal Deep Vein Thrombosis as adjudicated by the VTE events committee

  • Number of Participants With Total Deep Vein Thrombosis During Treatment Period [ Time Frame: First administration until 12-15 days ] [ Designated as safety issue: No ]
    Total Deep Vein Thrombosis as adjudicated by the VTE events committee

  • Number of Participants With Symptomatic Deep Vein Thrombosis During Treatment Period [ Time Frame: First administration until 12-15 days ] [ Designated as safety issue: No ]
    Symptomatic Deep Vein Thrombosis, confirmed by venous compression ultrasound, venography or autopsy, and as adjudicated by the VTE events committee

  • Number of Participants With Pulmonary Embolism During Treatment Period [ Time Frame: First administration until 12-15 days ] [ Designated as safety issue: No ]
    Pulmonary embolism confirmed by pulmonary V-Q scintigraphy, chest x-ray, pulmonary angiography, spiral CT or autopsy, and as adjudicated by the VTE events committee

  • Number of Participants Who Died During Treatment Period [ Time Frame: First administration until 12-15 days ] [ Designated as safety issue: No ]
    All cause death, as adjudicated by the VTE events committee

  • Number of Participants With Total Venous Thromboembolic Event (VTE) and All-cause Mortality During the Follow-up Period [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Total Venous Thromboembolic Event (VTE) includes both proximal and distal deep vein thrombosis (DVT) (detected by routine bilateral venography), symptomatic DVT (confirmed by venous compression ultrasound, venography or autopsy) and pulmonary embolism (PE) (confirmed by pulmonary V-Q scintigraphy, chest x-ray, pulmonary angiography, spiral CT or autopsy).

  • Number of Participants With Bleeding Events (Defined According to Modified McMaster Criteria) During Treatment Period [ Time Frame: First administration until 12-15 days ] [ Designated as safety issue: Yes ]

    Major bleeding events were defined as

    • 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

    Clinically-relevant was defined as

    • spontaneous skin hematoma greater than or equal to 25 cm²
    • wound hematoma greater than or equal to 100 cm²
    • spontaneous nose bleed lasting longer than 5 min
    • macroscopic hematuria spontaneous or lasting longer than 24 hours if associated with an intervention
    • spontaneous rectal bleeding (more than a spot on toilet paper)
    • gingival bleeding lasting longer than 5 min
    • any other bleeding event considered clinically relevant by the investigator

    Minor bleeding events were defined as all other bleeding events that did not fulfil the criteria from above.



Enrollment: 2615
Study Start Date: November 2004
Primary Completion Date: June 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dabigatran Dose 1
low dose regimen taken once daily
Drug: Dabigatran Dose 1 - day 2 to completion
low dose regimen taken once daily
Drug: Dabigatran Dose 1 - day 1
low dose regimen taken once daily
Experimental: Dabigatran Dose 2
high dose regimen taken once daily
Drug: Dabigatran Dose 2 - day 2 to completion
high dose regimen taken once daily
Drug: Dabigatran Dose 2 - day 1
high dose regimen taken once daily
Active Comparator: Enoxaparin
30 mg subcutaneously twice daily
Drug: Enoxaparin
30 mg subcutaneously twice daily

  Eligibility

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

Inclusion criteria INCLUSION CRITERIA

  1. Patients scheduled to undergo a primary, unilateral elective total knee repla cement.
  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.

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, arteriovenous (AV) malformation or aneurysm.
  7. History of VTE or pre-existing condition requiring anticoagulant therapy.
  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 6 months.
  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 < 30 mL/min). In order to determine patient inclusion/exclusion, creatinine clearance (CrCl) needs to be calculated only if serum creatinine is elevated or renal insufficiency is suspected.
  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: NCT00152971

  Show 94 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00152971     History of Changes
Other Study ID Numbers: 1160.24
Study First Received: September 8, 2005
Results First Received: November 18, 2010
Last Updated: April 22, 2014
Health Authority: Canada:
Great Britain:
Mexico:
United States: Food and Drug Administration

Additional relevant MeSH terms:
Thromboembolism
Venous Thromboembolism
Venous Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Thrombosis
Dabigatran
Enoxaparin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 26, 2014