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

April 22, 2014 updated by: Boehringer Ingelheim

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

2615

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada
        • 1160.24.02031 University of Alberta Hospital
      • Edmonton, Alberta, Canada
        • 1160.24.02036 2B2.37 Walter Mackenizie Centre
      • Red Deer, Alberta, Canada
        • 1160.24.02024 Red Deer Regional Hospital
    • British Columbia
      • Kelowna, British Columbia, Canada
        • 1160.24.02032 Kelowna General Hospital
      • Vancouver, British Columbia, Canada
        • 1160.24.02034 Hematology/Oncology Research
    • Manitoba
      • Winnipeg, Manitoba, Canada
        • 1160.24.02025 Grace General Hospital
    • New Brunswick
      • Fredericton, New Brunswick, Canada
        • 1160.24.02007 Orthopaedics 4NE
      • Saint John, New Brunswick, Canada
        • 1160.24.02027 Atlantic Health Sciences Corporation
    • Ontario
      • Ajax, Ontario, Canada
        • 1160.24.02021 Rouge Valley Health System
      • Barrie, Ontario, Canada
        • 1160.24.02008 Orthopaedic Surgery
      • Brantford, Ontario, Canada
        • 1160.24.02016 Orthopaedic Surgery
      • Burlington, Ontario, Canada
        • 1160.24.02010 Joseph Brant Memorial Hospital
      • Guelph, Ontario, Canada
        • 1160.24.02001 73 Delhi Street
      • Hamilton, Ontario, Canada
        • 1160.24.02014 565 Sanatorium Road
      • Kitchener, Ontario, Canada
        • 1160.24.02004 Grand River Hospital
      • Niagara Falls, Ontario, Canada
        • 1160.24.02028 NHS- Greater Niagara General Site
      • Oshawa, Ontario, Canada
        • 1160.24.02022 Lakeridge Health Oshawa
      • Ottawa, Ontario, Canada
        • 1160.24.02017 1053 Carling Avenue
      • Ottawa, Ontario, Canada
        • 1160.24.02026 Ottawa Hospital - General Campus
      • Richmond Hill, Ontario, Canada
        • 1160.24.02015 York Central Hospital Research
      • Scarborough, Ontario, Canada
        • 1160.24.02009 2863 Ellesmere Road
      • St. Catherine's, Ontario, Canada
        • 1160.24.02029 Niagara Health System St. Catharine's General Site
      • Stratford, Ontario, Canada
        • 1160.24.02003 46 General Hospital Drive
      • Thunder Bay, Ontario, Canada
        • 1160.24.02033 Thunder Bay Regional Hospital
      • Toronto, Ontario, Canada
        • 1160.24.02002 Toronto East General Hospital Fracture Clinic
      • Toronto, Ontario, Canada
        • 1160.24.02023 North York General Hospital
      • Toronto, Ontario, Canada
        • 1160.24.02030 St. Joseph's Health Centre
      • Welland, Ontario, Canada
        • 1160.24.02006 206-477 King Street
      • Weston, Ontario, Canada
        • 1160.24.02035 Humber River Regional Hospital
      • Windsor, Ontario, Canada
        • 1160.24.02011 Windsor Regional Hospital
      • Windsor, Ontario, Canada
        • 1160.24.02012 Hotel Dieu Grace Hospital
    • Prince Edward Island
      • Charlottetown, Prince Edward Island, Canada
        • 1160.24.02013 Queen Elizabeth Hospital
  • Mexico
      • Guadalajara, Jalisco, Mexico
        • 1160.24.05009 Traumatologia, Planta Baja
      • México, Mexico
        • 1160.24.05004
  • United Kingdom
      • London, United Kingdom
        • 1160.24.44001 Ravenscourt Park Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States
        • 1160.24.01074 Capstone Clinical Trials, Inc.
      • Northport, Alabama, United States
        • 1160.24.01079 West AL Research, Inc
    • Arizona
      • Tucson, Arizona, United States
        • 1160.24.01047 Tucson Orhtopaedic Institute
    • Arkansas
      • Little Rock, Arkansas, United States
        • 1160.24.01025 Martin, Bowen, Hefley Knee and Sports
      • Little Rock, Arkansas, United States
        • 1160.24.01053 OrthoArkansas, PA
      • Little Rock, Arkansas, United States
        • 1160.24.01085 Martin, Bowen, Hefley Knee and Sports
    • California
      • Encinitas, California, United States
        • 1160.24.01041 Core Orthopedic Medical Center
      • Glendale, California, United States
        • 1160.24.01034 Glendale Adventist Medical Center
      • La Jolla, California, United States
        • 1160.24.01005 Scripps Clinical Ctr for Orthopedic Rsrch & Educ
      • Long Beach, California, United States
        • 1160.24.01077 Long Beach VA Healthcare system
      • Orange, California, United States
        • 1160.24.01064 Orthopedic Specialty Institute
    • Colorado
      • Aurora, Colorado, United States
        • 1160.24.01031 Colorodo Orthopedic Consultants, PC
      • Denver, Colorado, United States
        • 1160.24.01027 Advanced Orthopedic and Sports Medicine Specialists, PC
      • Engelwood, Colorado, United States
        • 1160.24.01023 Orthopedic Physicians of Colorado, PC
    • Florida
      • Bay Pines, Florida, United States
        • 1160.24.01020 Bay Pines VA Medical Center
      • Brandon, Florida, United States
        • 1160.24.01024 Pulmonary Associates of Brandon Clinical Research
      • Clearwater, Florida, United States
        • 1160.24.01030 Alliance Research, Inc.
      • Deland, Florida, United States
        • 1160.24.01039 Florida Orthopedic Associates
      • Hollywood, Florida, United States
        • 1160.24.01036 Orthopaedic Associates of South Broward, PA
      • Melbourne, Florida, United States
        • 1160.24.01010 MIMA Century Research Associates
      • Miami, Florida, United States
        • 1160.24.01062 Miami Institute for Joint Reconstruction
      • Orlando, Florida, United States
        • 1160.24.01040 Southern Clinical Research Consultants
      • Pensacola, Florida, United States
        • 1160.24.01067 Baptist Clinical Research
      • Pinellas Park, Florida, United States
        • 1160.24.01001 Boehringer Ingelheim Investigational Site
      • Pinellas Park, Florida, United States
        • 1160.24.01017 Boehringer Ingelheim Investigational Site
      • Pinellas Park, Florida, United States
        • 1160.24.01019 Boehringer Ingelheim Investigational Site
      • Port Orange, Florida, United States
        • 1160.24.01029 Coastal Medical Research
      • Tampa, Florida, United States
        • 1160.24.01038 James A. Haley VA Hospital
    • Georgia
      • Atlanta, Georgia, United States
        • 1160.24.01063 Resurgens Orthopaedics
      • Atlanta, Georgia, United States
        • 1160.24.01072 Resurgeons Orthopedics
      • Lawrencville, Georgia, United States
        • 1160.24.01056 Southern Orthopaedic Specialists
    • Idaho
      • Boise, Idaho, United States
        • 1160.24.01028 Intermountain Research Center
    • Iowa
      • Des Moines, Iowa, United States
        • 1160.24.01022 Iowa Orthopedic Clinic
    • Kentucky
      • Lexington, Kentucky, United States
        • 1160.24.01008 Bluegrass Orthopedic/Musculoskeletal Research, LLC
    • Maryland
      • Baltimore, Maryland, United States
        • 1160.24.01070 Sinai Hospital of Baltimore
      • Towson, Maryland, United States
        • 1160.24.01007 Ortho Associates
    • Missouri
      • Kansas City, Missouri, United States
        • 1160.24.01059 Rockhill Orthopaedics
    • Montana
      • Missoula, Montana, United States
        • 1160.24.01042 Center for Joint Care
    • North Carolina
      • Charlotte, North Carolina, United States
        • 1160.24.01014 Charlotte Orthopedic Specialists
    • Ohio
      • Cincinnati, Ohio, United States
        • 1160.24.01035 Wellington Orthopedics and Sports Medicine
    • Oklahoma
      • Oklahoma City, Oklahoma, United States
        • 1160.24.01006 VA Medical Center
      • Tulsa, Oklahoma, United States
        • 1160.24.01044 Tulsa Bone and Joint Associates
    • Oregon
      • Bend, Oregon, United States
        • 1160.24.01002 The Orthopedic and Neurological Center of the Cascades
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
        • 1160.24.01046 Boehringer Ingelheim Investigational Site
    • South Carolina
      • Charleston, South Carolina, United States
        • 1160.24.01016
      • Conway, South Carolina, United States
        • 1160.24.01073 Coastal Orthopedic Associates, PA
    • Texas
      • Austin, Texas, United States
        • 1160.24.01032 Seton Medical Center
      • Dallas, Texas, United States
        • 1160.24.01003 Texas Orthopedic Associates
      • Dallas, Texas, United States
        • 1160.24.01090 VA Medical Center
      • Houston, Texas, United States
        • 1160.24.01026 James Muntz, MD
      • Houston, Texas, United States
        • 1160.24.01033 Bone and Joint Clinic of Houston
      • Houston, Texas, United States
        • 1160.24.01076 Discovery Alliance
      • Lubbock, Texas, United States
        • 1160.24.01018 Gill Research Center
      • Plano, Texas, United States
        • 1160.24.01069 Correspondence and Pateint vists
      • San Antonio, Texas, United States
        • 1160.24.01015 Unlimited Research, LP
    • Virginia
      • Alexandria, Virginia, United States
        • 1160.24.01012 Anderson Orthopedic Clinic
    • Washington
      • Seattle, Washington, United States
        • 1160.24.01052 Swedish Medical Center
      • Spokane, Washington, United States
        • 1160.24.01057 Orthopedic Specialty Clinic of Spokane, PLLC
      • Tacoma, Washington, United States
        • 1160.24.01082 MultiCare Health System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Total Venous Thromboembolic Event and All-cause Mortality During Treatment Period
Time Frame: First administration until 12-15 days

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.
First administration until 12-15 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Major Venous Thromboembolic Event (VTE) is defined as proximal DVT and PE, as adjudicated by the VTE events committee
First administration until 12-15 days
Number of Participants With Proximal Deep Vein Thrombosis During Treatment Period
Time Frame: First administration until 12-15 days
Proximal Deep Vein Thrombosis as adjudicated by the VTE events committee
First administration until 12-15 days
Number of Participants With Total Deep Vein Thrombosis During Treatment Period
Time Frame: First administration until 12-15 days
Total Deep Vein Thrombosis as adjudicated by the VTE events committee
First administration until 12-15 days
Number of Participants With Symptomatic Deep Vein Thrombosis During Treatment Period
Time Frame: First administration until 12-15 days
Symptomatic Deep Vein Thrombosis, confirmed by venous compression ultrasound, venography or autopsy, and as adjudicated by the VTE events committee
First administration until 12-15 days
Number of Participants With Pulmonary Embolism During Treatment Period
Time Frame: First administration until 12-15 days
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
First administration until 12-15 days
Number of Participants Who Died During Treatment Period
Time Frame: First administration until 12-15 days
All cause death, as adjudicated by the VTE events committee
First administration until 12-15 days
Number of Participants With Total Venous Thromboembolic Event (VTE) and All-cause Mortality During the Follow-up Period
Time Frame: 3 months
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).
3 months
Number of Participants With Bleeding Events (Defined According to Modified McMaster Criteria) During Treatment Period
Time Frame: First administration until 12-15 days

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.
First administration until 12-15 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2004

Primary Completion (Actual)

June 1, 2006

Study Completion

December 7, 2022

Study Registration Dates

First Submitted

September 8, 2005

First Submitted That Met QC Criteria

September 8, 2005

First Posted (Estimate)

September 12, 2005

Study Record Updates

Last Update Posted (Estimate)

May 5, 2014

Last Update Submitted That Met QC Criteria

April 22, 2014

Last Verified

April 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1160.24

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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