Clinical trial NCT00371683: Study of Apixaban for the Prevention of Thrombosis-related Events Following Knee Replacement Surgery
Official title: A Phase 3 Randomized, Double-Blind Active-Controlled (Enoxaparin), Parallel-Group, Multi-Center Study to Evaluate the Safety and Efficacy of Oral Apixaban in Subjects Undergoing Elective Total Knee Replacement Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Deep Vein Thrombosis
Pulmonary Embolism
Keywords: Prevention of deep vein thrombosis and pulmonary embolism after total knee replacement surgery
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2006-09-04
Enrollment: 3608
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: The purpose of this study is to learn if apixaban can prevent blood clots in the leg (deep vein Thrombosis \[DVT\]) and lung (pulmonary embolism \[PE\]) that sometimes occur after knee replacement surgery and to learn how apixaban compares to enoxaparin (Lovenox®) for preventing these clots. The safety of apixaban will also be studied.


Eligibility criteria: Key Inclusion Criteria:

* Men and non-pregnant, non-breastfeeding women
* 18 years or older
* Scheduled for knee replacement surgery

Key Exclusion Criteria:

* hereditary or acquired bleeding disorders
* clotting disorders
* bleeding or high risk for bleeding
* drugs that affect bleeding or coagulation
* need for ongoing parenteral or oral anticoagulation

Primary outcomes:
measure: Event Rate of the Composite of Adjudicated Venous Thromboembolism (VTE) Events and All-Cause Death With Onset During the Intended Treatment Period - Primary Subjects
timeFrame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
measure: Event Rate for Participants With Major Bleeding, Clinically Relevant Non-Major Bleeding, Major or Clinically Relevant Non-Major Bleeding, Any Bleeding With Onset During the Treatment Period - Treated Population
timeFrame: First dose of study drug to last dose, plus 2 days post last dose
measure: Event Rate for Participants With Major Bleeding, Clinically Relevant (CR) Non-Major (N-M) Bleeding , Major or Clinically Relevant (CR) Non-Major (N-M) Bleeding, Any Bleeding With Onset During the Follow-Up Period
timeFrame: Last dose of study drug to Day 72 (60 days)
Secondary outcomes:
measure: Event Rate of Composite of Adjudicated Proximal DVT, Non-Fatal PE and All-Cause Death With Onset During the Intended Treatment Period PE and All-cause Death During the Intended Treatment Period
timeFrame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
measure: Event Rate of Adjudicated VTE / VTE-related Death With Onset During the Treatment Period
timeFrame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
measure: Event Rate for Participants With Proximal DVT/Non-Fatal PE/ VTE-Related Death With Onset During the Intended Treatment Period
timeFrame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
measure: Event Rate for Total Participants With Adjudicated VTE/All-Cause Death With Onset During the Intended Treatment Period
timeFrame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
measure: Event Rate for Total Participants With VTE/ VTE-Related Death With Onset During the Intended Treatment Period
timeFrame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
measure: Event Rate for Participants With All-Cause Death During the Intended Treatment Period
timeFrame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
measure: Event Rate for Participants With VTE-Related Death With Onset During the Intended Treatment Period
timeFrame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
measure: Event Rate for Participants With Symptomatic VTE/ All-Cause Death With Onset During the Intended Treatment Period
timeFrame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
measure: Event Rate for Participants With Symptomatic VTE/ VTE-Related Death With Onset During the Intended Treatment Period
timeFrame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
measure: Event Rate for Participants With VTE/Major Bleeding/All-Cause Death With Onset During the Intended Treatment Period
timeFrame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
measure: Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period
timeFrame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
measure: Event Rate for Participants With Proximal DVT, Distal DVT, Asymptomatic Proximal DVT, Asymptomatic Distal DVT With Onset During the Intended Treatment Period
timeFrame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
measure: Event Rate for Participants With Adjudicated Myocardial Infarction (MI) Acute Ischemic Stroke and Thromboembolic Events With Onset During the Treatment Period
timeFrame: From first dose to last dose, plus 2 days (12 days, plus 2)
measure: Event Rate of Adjudicated MI, Stroke, and Thrombocytopenia Events During the Follow-Up Period
timeFrame: Post last dose of study drug to Day 72 (60 days)
measure: Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), AEs Leading to Discontinuation, and Deaths - Treated Population
timeFrame: First dose to last dose, plus 2 days for AEs (12 + 2 days) or plus 30 days for SAEs (12 + 30 days)
measure: Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period
timeFrame: Baseline to last dose of study drug, plus 2 days
measure: Mean Change From Baseline in Heart Rate During the Treatment Period
timeFrame: Baseline to last dose of study drug, plus 2 days
measure: Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period
timeFrame: First dose to last dose of study drug (12 days), plus 2 days
measure: Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period
timeFrame: First dose to last dose of study drug (12 days), plus 2 days
measure: Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period
timeFrame: First dose to last dose of study drug (12 days), plus 2 days
measure: Number of Participants With Other Chemistry Laboratory Marked Abnormalities During the Treatment Period
timeFrame: First dose to last dose of study drug (12 days), plus 2 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Capstone Clinical Trials, Inc
state: Alabama
city: Birmingham
country: United States
facility: Capstone Clinical Trials, Inc
state: Alabama
city: Tuscaloosa
country: United States
facility: West Alabama Research, Inc.
state: Alabama
city: Little Rock
country: United States
facility: Martin Bowen Hefley Orthopedics
state: Arkansas
city: Aurora
country: United States
facility: Colorado Orthopedic Consultants, Pc
state: Colorado
city: Denver
country: United States
facility: Colorado Joint Replacement
state: Colorado
city: Denver
country: United States
facility: Jdpmedical Research
state: Colorado
city: Englewood
country: United States
facility: Orhtopaedic Physicians Of Colorado, P.C.
state: Colorado
city: Hartford
country: United States
facility: Orthopedics Assocs Of Hartford
state: Connecticut
city: Washington
country: United States
facility: Anthony S. Unger, Md
state: District of Columbia
city: Bay Pines
country: United States
facility: Bay Pines Va Medical Center
state: Florida
city: Brandon
country: United States
facility: Pab Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center For Clinical Research
state: Florida
city: Orange City
country: United States
facility: Mark W. Hollmann, Md
state: Florida
city: Winter Park
country: United States
facility: Jewett Orthopaedic Clinic
state: Florida
city: Decatur
country: United States
facility: Atlanta Knee And Sports Medicine
state: Georgia
city: Boise
country: United States
facility: Americana Orthopedics
state: Idaho
city: Boise
country: United States
facility: Intermountain Orthopaedics
state: Idaho
city: Lexington
country: United States
facility: Bluegrass Orthopaedics/Bmr
state: Kentucky
city: Charleston
country: United States
facility: Charleston Orthopaedic Assocs.
state: South Carolina
city: Houston
country: United States
facility: Kelsey Seybold Clinic
state: Texas
city: Houston
country: United States
facility: Bone & Joint Clinic Of Houston
state: Texas
city: Lubbock
country: United States
facility: Gill Orthopedic Center
state: Texas
city: Lubbock
country: United States
facility: Robert R. King, Md
state: Texas
city: San Antonio
country: United States
facility: Unlimited Research
state: Texas
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Cordoba
country: Argentina
facility: Local Institution
city: Garran
country: Australia
facility: Local Institution
state: Australian Capital Territory
city: Camperdown
country: Australia
facility: Local Institution
state: New South Wales
city: Caringbah
country: Australia
facility: Local Institution
state: New South Wales
city: Lismore
country: Australia
facility: Local Institution
state: New South Wales
city: Gold Coast
country: Australia
facility: Local Institution
state: Queensland
city: Adelaide
country: Australia
facility: Local Institution
state: South Australia
city: Bedford Park
country: Australia
facility: Local Institution
state: South Australia
city: Box Hill
country: Australia
facility: Local Institution
state: Victoria
city: Windsor
country: Australia
facility: Local Institution
state: Victoria
city: Perth
country: Australia
facility: Local Institution
state: Western Australia
city: Curitiba
country: Brazil
facility: Local Institution
state: Parana
city: Porto Alegre, Rs
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Campinas
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Edmonton
country: Canada
facility: Local Institution
state: Alberta
city: Ajax
country: Canada
facility: Local Institution
state: Ontario
city: Burlington
country: Canada
facility: Local Institution
state: Ontario
city: Cambridge
country: Canada
facility: Local Institution
state: Ontario
city: Chatham
country: Canada
facility: Local Institution
state: Ontario
city: Dartmouth
country: Canada
facility: Local Institution
state: Ontario
city: Guelph
country: Canada
facility: Local Institution
state: Ontario
city: Lindsay
country: Canada
facility: Local Institution
state: Ontario
city: Newmarket
country: Canada
facility: Local Institution
state: Ontario
city: Niagara Falls
country: Canada
facility: Local Institution
state: Ontario
city: Sarnia
country: Canada
facility: Local Institution
state: Ontario
city: Scarborough
country: Canada
facility: Local Institution
state: Ontario
city: Scarborough
country: Canada
facility: Local Institution
state: Ontario
city: St. Catharines
country: Canada
facility: Local Institution
state: Ontario
city: Stratford
country: Canada
facility: Local Institution
state: Ontario
city: Waterloo
country: Canada
facility: Local Institution
state: Ontario
city: Windsor
country: Canada
facility: Local Institution
state: Ontario
city: Charlottetown
country: Canada
facility: Local Institution
state: Prince Edward Island
city: Montreal
country: Canada
facility: Local Institution
state: Quebec
city: Quebec
country: Canada
facility: Local Institution
city: Horsholm
country: Denmark
facility: Local Institution
city: Kopenhamn S
country: Denmark
facility: Local Institution
city: Kecskemet
country: Hungary
facility: Local Institution
city: Szekesfehervar
country: Hungary
facility: Local Institution
city: Szolnok
country: Hungary
facility: Local Institution
city: Afula
country: Israel
facility: Local Institution
city: Beer-Sheva
country: Israel
facility: Local Institution
city: Haifa
country: Israel
facility: Local Institution
city: Holon
country: Israel
facility: Local Institution
city: Kfar-Saba
country: Israel
facility: Local Institution
city: Petach-Tikva
country: Israel
facility: Local Institution
city: Rehovot
country: Israel
facility: Local Institution
city: Zerifin
country: Israel
facility: Local Institution
city: Tijuana
country: Mexico
facility: Local Institution
state: Baja California
city: Df
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Df
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Df
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Cd Madero
country: Mexico
facility: Local Institution
state: Tamaulipas
city: Jalapa
country: Mexico
facility: Local Institution
state: Veracruz
city: Merida
country: Mexico
facility: Local Institution
state: Yucatan
city: Merida
country: Mexico
facility: Local Institution
state: Yucatan
city: Chihuahua
country: Mexico
facility: Local Institution
city: Bialystok
country: Poland
facility: Local Institution
city: Krakow
country: Poland
facility: Local Institution
city: Lodz
country: Poland
facility: Local Institution
city: Lublin
country: Poland
facility: Local Institution
city: Szczecin
country: Poland
facility: Local Institution
city: Warszawa
country: Poland
facility: Local Institution
city: Warszawa
country: Poland
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Samara
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: Goteborg
country: Sweden
facility: Local Institution
city: Adana
country: Turkey
facility: Local Institution
city: Bursa
country: Turkey
facility: Local Institution
city: Mersin
country: Turkey
facility: Local Institution
city: Trabzon
country: Turkey
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Jamieson MJ, Byon W, Dettloff RW, Crawford M, Gargalovic PS, Merali SJ, Onorato J, Quintero AJ, Russ C. Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data. Am J Cardiovasc Drugs. 2022 Nov;22(6):615-631. doi: 10.1007/s40256-022-00524-x. Epub 2022 May 16.
citation: Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Portman RJ. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med. 2009 Aug 6;361(6):594-604. doi: 10.1056/NEJMoa0810773.