Clinical trial NCT00152971: Dabigatran Etexilate vs Enoxaparin in Prevention of Venous Thromboembolism (VTE) Post Total Knee Replacement
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Arthroplasty, Replacement, Knee
Thromboembolism
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2005-09-12
Enrollment: 2615
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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


Eligibility 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.

Primary outcomes:
measure: Number of Participants With Total Venous Thromboembolic Event and All-cause Mortality During Treatment Period
timeFrame: First administration until 12-15 days
Secondary outcomes:
measure: Number of Participants With Major Venous Thromboembolic Event and Venous Thromboembolic Event-related Mortality During Treatment Period
timeFrame: First administration until 12-15 days
measure: Number of Participants With Proximal Deep Vein Thrombosis During Treatment Period
timeFrame: First administration until 12-15 days
measure: Number of Participants With Total Deep Vein Thrombosis During Treatment Period
timeFrame: First administration until 12-15 days
measure: Number of Participants With Symptomatic Deep Vein Thrombosis During Treatment Period
timeFrame: First administration until 12-15 days
measure: Number of Participants With Pulmonary Embolism During Treatment Period
timeFrame: First administration until 12-15 days
measure: Number of Participants Who Died During Treatment Period
timeFrame: First administration until 12-15 days
measure: Number of Participants With Total Venous Thromboembolic Event (VTE) and All-cause Mortality During the Follow-up Period
timeFrame: 3 months
measure: Number of Participants With Bleeding Events (Defined According to Modified McMaster Criteria) During Treatment Period
timeFrame: First administration until 12-15 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: 1160.24.01074 Capstone Clinical Trials, Inc.
state: Alabama
city: Northport
country: United States
facility: 1160.24.01079 West AL Research, Inc
state: Alabama
city: Tucson
country: United States
facility: 1160.24.01047 Tucson Orhtopaedic Institute
state: Arizona
city: Little Rock
country: United States
facility: 1160.24.01025 Martin, Bowen, Hefley Knee and Sports
state: Arkansas
city: Little Rock
country: United States
facility: 1160.24.01053 OrthoArkansas, PA
state: Arkansas
city: Little Rock
country: United States
facility: 1160.24.01085 Martin, Bowen, Hefley Knee and Sports
state: Arkansas
city: Encinitas
country: United States
facility: 1160.24.01041 Core Orthopedic Medical Center
state: California
city: Glendale
country: United States
facility: 1160.24.01034 Glendale Adventist Medical Center
state: California
city: La Jolla
country: United States
facility: 1160.24.01005 Scripps Clinical Ctr for Orthopedic Rsrch & Educ
state: California
city: Long Beach
country: United States
facility: 1160.24.01077 Long Beach VA Healthcare system
state: California
city: Orange
country: United States
facility: 1160.24.01064 Orthopedic Specialty Institute
state: California
city: Aurora
country: United States
facility: 1160.24.01031 Colorodo Orthopedic Consultants, PC
state: Colorado
city: Denver
country: United States
facility: 1160.24.01027 Advanced Orthopedic and Sports Medicine Specialists, PC
state: Colorado
city: Engelwood
country: United States
facility: 1160.24.01023 Orthopedic Physicians of Colorado, PC
state: Colorado
city: Bay Pines
country: United States
facility: 1160.24.01020 Bay Pines VA Medical Center
state: Florida
city: Brandon
country: United States
facility: 1160.24.01024 Pulmonary Associates of Brandon Clinical Research
state: Florida
city: Clearwater
country: United States
facility: 1160.24.01030 Alliance Research, Inc.
state: Florida
city: Deland
country: United States
facility: 1160.24.01039 Florida Orthopedic Associates
state: Florida
city: Hollywood
country: United States
facility: 1160.24.01036 Orthopaedic Associates of South Broward, PA
state: Florida
city: Melbourne
country: United States
facility: 1160.24.01010 MIMA Century Research Associates
state: Florida
city: Miami
country: United States
facility: 1160.24.01062 Miami Institute for Joint Reconstruction
state: Florida
city: Orlando
country: United States
facility: 1160.24.01040 Southern Clinical Research Consultants
state: Florida
city: Pensacola
country: United States
facility: 1160.24.01067 Baptist Clinical Research
state: Florida
city: Pinellas Park
country: United States
facility: 1160.24.01001 Boehringer Ingelheim Investigational Site
state: Florida
city: Pinellas Park
country: United States
facility: 1160.24.01017 Boehringer Ingelheim Investigational Site
state: Florida
city: Pinellas Park
country: United States
facility: 1160.24.01019 Boehringer Ingelheim Investigational Site
state: Florida
city: Port Orange
country: United States
facility: 1160.24.01029 Coastal Medical Research
state: Florida
city: Tampa
country: United States
facility: 1160.24.01038 James A. Haley VA Hospital
state: Florida
city: Atlanta
country: United States
facility: 1160.24.01063 Resurgens Orthopaedics
state: Georgia
city: Atlanta
country: United States
facility: 1160.24.01072 Resurgeons Orthopedics
state: Georgia
city: Lawrencville
country: United States
facility: 1160.24.01056 Southern Orthopaedic Specialists
state: Georgia
city: Boise
country: United States
facility: 1160.24.01028 Intermountain Research Center
state: Idaho
city: Des Moines
country: United States
facility: 1160.24.01022 Iowa Orthopedic Clinic
state: Iowa
city: Lexington
country: United States
facility: 1160.24.01008 Bluegrass Orthopedic/Musculoskeletal Research, LLC
state: Kentucky
city: Baltimore
country: United States
facility: 1160.24.01070 Sinai Hospital of Baltimore
state: Maryland
city: Towson
country: United States
facility: 1160.24.01007 Ortho Associates
state: Maryland
city: Kansas City
country: United States
facility: 1160.24.01059 Rockhill Orthopaedics
state: Missouri
city: Missoula
country: United States
facility: 1160.24.01042 Center for Joint Care
state: Montana
city: Charlotte
country: United States
facility: 1160.24.01014 Charlotte Orthopedic Specialists
state: North Carolina
city: Cincinnati
country: United States
facility: 1160.24.01035 Wellington Orthopedics and Sports Medicine
state: Ohio
city: Oklahoma City
country: United States
facility: 1160.24.01006 VA Medical Center
state: Oklahoma
city: Tulsa
country: United States
facility: 1160.24.01044 Tulsa Bone and Joint Associates
state: Oklahoma
city: Bend
country: United States
facility: 1160.24.01002 The Orthopedic and Neurological Center of the Cascades
state: Oregon
city: Philadelphia
country: United States
facility: 1160.24.01046 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: 1160.24.01016
state: South Carolina
city: Conway
country: United States
facility: 1160.24.01073 Coastal Orthopedic Associates, PA
state: South Carolina
city: Austin
country: United States
facility: 1160.24.01032 Seton Medical Center
state: Texas
city: Dallas
country: United States
facility: 1160.24.01003 Texas Orthopedic Associates
state: Texas
city: Dallas
country: United States
facility: 1160.24.01090 VA Medical Center
state: Texas
city: Houston
country: United States
facility: 1160.24.01026 James Muntz, MD
state: Texas
city: Houston
country: United States
facility: 1160.24.01033 Bone and Joint Clinic of Houston
state: Texas
city: Houston
country: United States
facility: 1160.24.01076 Discovery Alliance
state: Texas
city: Lubbock
country: United States
facility: 1160.24.01018 Gill Research Center
state: Texas
city: Plano
country: United States
facility: 1160.24.01069 Correspondence and Pateint vists
state: Texas
city: San Antonio
country: United States
facility: 1160.24.01015 Unlimited Research, LP
state: Texas
city: Alexandria
country: United States
facility: 1160.24.01012 Anderson Orthopedic Clinic
state: Virginia
city: Seattle
country: United States
facility: 1160.24.01052 Swedish Medical Center
state: Washington
city: Spokane
country: United States
facility: 1160.24.01057 Orthopedic Specialty Clinic of Spokane, PLLC
state: Washington
city: Tacoma
country: United States
facility: 1160.24.01082 MultiCare Health System
state: Washington
city: Edmonton
country: Canada
facility: 1160.24.02031 University of Alberta Hospital
state: Alberta
city: Edmonton
country: Canada
facility: 1160.24.02036 2B2.37 Walter Mackenizie Centre
state: Alberta
city: Red Deer
country: Canada
facility: 1160.24.02024 Red Deer Regional Hospital
state: Alberta
city: Kelowna
country: Canada
facility: 1160.24.02032 Kelowna General Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: 1160.24.02034 Hematology/Oncology Research
state: British Columbia
city: Winnipeg
country: Canada
facility: 1160.24.02025 Grace General Hospital
state: Manitoba
city: Fredericton
country: Canada
facility: 1160.24.02007 Orthopaedics 4NE
state: New Brunswick
city: Saint John
country: Canada
facility: 1160.24.02027 Atlantic Health Sciences Corporation
state: New Brunswick
city: Ajax
country: Canada
facility: 1160.24.02021 Rouge Valley Health System
state: Ontario
city: Barrie
country: Canada
facility: 1160.24.02008 Orthopaedic Surgery
state: Ontario
city: Brantford
country: Canada
facility: 1160.24.02016 Orthopaedic Surgery
state: Ontario
city: Burlington
country: Canada
facility: 1160.24.02010 Joseph Brant Memorial Hospital
state: Ontario
city: Guelph
country: Canada
facility: 1160.24.02001 73 Delhi Street
state: Ontario
city: Hamilton
country: Canada
facility: 1160.24.02014 565 Sanatorium Road
state: Ontario
city: Kitchener
country: Canada
facility: 1160.24.02004 Grand River Hospital
state: Ontario
city: Niagara Falls
country: Canada
facility: 1160.24.02028 NHS- Greater Niagara General Site
state: Ontario
city: Oshawa
country: Canada
facility: 1160.24.02022 Lakeridge Health Oshawa
state: Ontario
city: Ottawa
country: Canada
facility: 1160.24.02017 1053 Carling Avenue
state: Ontario
city: Ottawa
country: Canada
facility: 1160.24.02026 Ottawa Hospital - General Campus
state: Ontario
city: Richmond Hill
country: Canada
facility: 1160.24.02015 York Central Hospital Research
state: Ontario
city: Scarborough
country: Canada
facility: 1160.24.02009 2863 Ellesmere Road
state: Ontario
city: St. Catherine's
country: Canada
facility: 1160.24.02029 Niagara Health System St. Catharine's General Site
state: Ontario
city: Stratford
country: Canada
facility: 1160.24.02003 46 General Hospital Drive
state: Ontario
city: Thunder Bay
country: Canada
facility: 1160.24.02033 Thunder Bay Regional Hospital
state: Ontario
city: Toronto
country: Canada
facility: 1160.24.02002 Toronto East General Hospital Fracture Clinic
state: Ontario
city: Toronto
country: Canada
facility: 1160.24.02023 North York General Hospital
state: Ontario
city: Toronto
country: Canada
facility: 1160.24.02030 St. Joseph's Health Centre
state: Ontario
city: Welland
country: Canada
facility: 1160.24.02006 206-477 King Street
state: Ontario
city: Weston
country: Canada
facility: 1160.24.02035 Humber River Regional Hospital
state: Ontario
city: Windsor
country: Canada
facility: 1160.24.02011 Windsor Regional Hospital
state: Ontario
city: Windsor
country: Canada
facility: 1160.24.02012 Hotel Dieu Grace Hospital
state: Ontario
city: Charlottetown
country: Canada
facility: 1160.24.02013 Queen Elizabeth Hospital
state: Prince Edward Island
city: Guadalajara, Jalisco
country: Mexico
facility: 1160.24.05009 Traumatologia, Planta Baja
city: México
country: Mexico
facility: 1160.24.05004
city: London
country: United Kingdom
facility: 1160.24.44001 Ravenscourt Park Hospital
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Rosencher N, Noack H, Feuring M, Clemens A, Friedman RJ, Eriksson BI. Type of anaesthesia and the safety and efficacy of thromboprophylaxis with enoxaparin or dabigatran etexilate in major orthopaedic surgery: pooled analysis of three randomized controlled trials. Thromb J. 2012 Jun 18;10(1):9. doi: 10.1186/1477-9560-10-9.