Clinical trial NCT00423319: Study of an Investigational Drug for the Prevention of Thrombosis-related Events Following Hip Replacement Surgery (ADVANCE-3)
Official title: A Phase 3 Randomized, Double-blind, Active-controlled, Parallel-group, Multi-center Study to Evaluate the Safety and Efficacy of Apixaban in Subjects Undergoing Elective Total Hip Replacement Surgery (The Advance-3 Study Apixaban Dosed Orally Versus Anticoagulation With Injectable Enoxaparin to Prevent Venous Thromboembolism)
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 hip replacement surgery
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2007-01-18
Enrollment: 5407
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 whether apixaban can prevent the blood clots in the leg (deep vein thrombosis) and lung (pulmonary embolism) that sometimes occur after hip replacement surgery and to learn how apixaban compares with enoxaparin in preventing these clots. The safety of apixaban will also be studied


Eligibility criteria: Key Inclusion Criteria

* Patients undergoing elective unilateral total hip replacement or a revision of at least 1 component of a total hip replacement.
* Patients who were willing and able to undergo bilateral ascending contrast venography
* Either sex, any race, 18 years and older

Key Exclusion Criteria

* Known or suspected bleeding or coagulation disorder in the patient or his or her first-degree relative
* Known or suspected history of heparin-induced thrombocytopenia
* Known coagulopathy
* Active bleeding or at high risk for bleeding
* Brain, spinal, ophthalmologic, or major surgery or trauma within the past 90 days
* Active hepatobiliary disease
* Alcohol and/or substance abuse within the past year
* Any condition for which surgery or administration of an anticoagulant is contraindicated
* Two consecutive blood pressure readings within 15 to 30 minutes with supine systolic blood pressure \>180 mm Hg or supine diastolic blood pressure \>105 mm Hg
* Clinically significant laboratory abnormalities at the enrollment visit:
* Hemoglobin \<10 g/dL
* Platelet count \<100,000/mm\^3
* Creatinine clearance \<30 mL/min, as estimated by the method of Cockcroft and Gault
* Alanine aminotransferase or aspartate aminotransferase \>2\*upper limit of normal or a total bilirubin ≥ 1.5\*1 (unless an alternative causative factor such as Gilbert's syndrome was identified)
* Need for ongoing treatment with a parenteral or oral anticoagulant (eg, subjects with mechanical valves, warfarin eligible atrial fibrillation)
* Current use of dextrans or fibrinolytics
* Treatment with medications affecting coagulation or platelet function

Primary outcomes:
measure: Rate of Composite of Adjudicated Venous Thromboembolic Event (VTE)-Related (Pulmonary Embolism and Symptomatic and Asymptomatic Deep Vein Thrombosis[DVT]) and All-cause Death During the Intended Treatment Period
timeFrame: Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose
Secondary outcomes:
measure: Rate of Composite of Adjudicated Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism, and Venous Thromboembolic Event-related Death With Onset During Intended Treatment Period
timeFrame: Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose
measure: Rates of Adjudicated All-cause Death, VTE-related Death, Pulmonary Embolism (PE), Nonfatal PE, Deep Vein Thrombosis (DVT) (Symptomatic and Asymptomatic), Symptomatic and Asymptomatic Proximal and Distal DVT During the Intended Treatment Period
timeFrame: Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose
measure: Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), Major or CRNM, and Any Bleeding During the Treatment Period
timeFrame: First dose of study drug (presurgery) through 2 days after the last dose of study drug
measure: Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), and Death as Outcome
timeFrame: First dose of study drug (presurgery) through 30 days after the last dose of study drug
measure: Number of Participants With a Bleeding-related Adverse Event During the Treatment Period
timeFrame: First dose of study drug (presurgery) through 2 days after the last dose of study drug
measure: Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
timeFrame: First dose of study drug (presurgery) through 2 days after the last dose of study drug
measure: Number of Participants With a Bleeding-related Adverse Event During the Treatment Period (Continued)
timeFrame: First dose of study drug (presurgery) through 2 days after the last dose of study drug
measure: Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
timeFrame: First dose of study drug (presurgery) through 2 days after the last dose of study drug
measure: Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period
timeFrame: First dose of study drug (presurgery) through 2 days after the last dose of study drug
measure: Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
timeFrame: First dose of study drug (presurgery) through 2 days after the last dose of study drug
measure: Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
timeFrame: First dose of study drug (presurgery) through 2 days after the last dose of study drug
measure: Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
timeFrame: First dose of study drug (presurgery) through 30 days after the last dose of study drug
measure: Rates of Adjudicated Myocardial Infarction (MI)/Stroke, MI, Stroke, and Thrombocytopenia During the Intended Treatment Period
timeFrame: Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Capstone Clinical Trials, Inc
state: Alabama
city: Birmingham
country: United States
facility: West Alabama Research, Llc
state: Alabama
city: Little Rock
country: United States
facility: Martin Bowen Hefley Orthopedics
state: Arkansas
city: Little Rock
country: United States
facility: Orthoarkansas, P.A.
state: Arkansas
city: Sacramento
country: United States
facility: Uc Davis Medical Center
state: California
city: Aurora
country: United States
facility: Colorado Orthopedic Consultants, Pc
state: Colorado
city: Denver
country: United States
facility: Advanced Orthopedic And Sports Medicine Specilists
state: Colorado
city: Denver
country: United States
facility: Denver-Vail Orthopedics, P.C.
state: Colorado
city: Brandon
country: United States
facility: Pab Clinical Research
state: Florida
city: Clearwater
country: United States
facility: Research Alliance, Inc.
state: Florida
city: Ft. Lauderdale
country: United States
facility: Shrock Orthopedic Research
state: Florida
city: Tamarac
country: United States
facility: Phoenix Clinical Research, Llc
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: Meridian
country: United States
facility: Bosie Orthopedic Clinic
state: Idaho
city: Altoona
country: United States
facility: University Orthopedic Center
state: Pennsylvania
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: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Ciudad De Buenos Aires
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Coronel Suarez
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Monte Grande
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Camperdown
country: Australia
facility: Local Institution
state: New South Wales
city: Kogarah
country: Australia
facility: Local Institution
state: New South Wales
city: Lismore
country: Australia
facility: Local Institution
state: New South Wales
city: Southport
country: Australia
facility: Local Institution
state: Queensland
city: Bedford Park
country: Australia
facility: Local Institution
state: South Australia
city: Box Hill
country: Australia
facility: Local Institution
state: Victoria
city: Malvern
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: Antwerp
country: Belgium
facility: Local Institution
city: Brasschaat
country: Belgium
facility: Local Institution
city: Genk
country: Belgium
facility: Local Institution
city: Hasselt
country: Belgium
facility: Local Institution
city: Leuven
country: Belgium
facility: Local Institution
city: Edmonton
country: Canada
facility: Local Institution
state: Alberta
city: Ajax
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: Guelph
country: Canada
facility: Local Institution
state: Ontario
city: Newmarket
country: Canada
facility: Local Institution
state: Ontario
city: Oshawa
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: 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: Montreal
country: Canada
facility: Local Institution
state: Quebec
city: Quebec
country: Canada
facility: Local Institution
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Guangzhou
country: China
facility: Local Institution
state: Guangdong
city: Qingdao
country: China
facility: Local Institution
state: Shandong
city: Shanghai
country: China
facility: Local Institution
state: Shanghai
city: Shanghai
country: China
facility: Local Institution
state: Shanghai
city: Shanghai
country: China
facility: Local Institution
state: Shanghai
city: Amager
country: Denmark
facility: Local Institution
city: Frederiksberg
country: Denmark
facility: Local Institution
city: Herlev
country: Denmark
facility: Local Institution
city: Horsholm
country: Denmark
facility: Local Institution
city: Hvidovre
country: Denmark
facility: Local Institution
city: Kobenhavn Nv
country: Denmark
facility: Local Institution
city: Silkeborg
country: Denmark
facility: Local Institution
city: Nice
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Saint Etienne
country: France
facility: Local Institution
city: Saint-Saulve
country: France
facility: Local Institution
city: Frankfurt / Main
country: Germany
facility: Local Institution
city: Frankfurt
country: Germany
facility: Local Institution
city: Rheinfelden
country: Germany
facility: Local Institution
city: Budapest
country: Hungary
facility: Local Institution
city: Kecskemet
country: Hungary
facility: Local Institution
city: Szeged
country: Hungary
facility: Local Institution
city: Szolnok
country: Hungary
facility: Local Institution
city: Ahmedabad
country: India
facility: Local Institution
state: Gujarat
city: Ludhiana
country: India
facility: Local Institution
state: Punjab
city: Lucknow
country: India
facility: Local Institution
state: Uttar Prsdesh
city: Bangalore
country: India
facility: Local Institution
city: Mangalore
country: India
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: Zerifin
country: Israel
facility: Local Institution
city: Tijuana
country: Mexico
facility: Local Institution
state: Baja California
city: Mexico City
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Mexico City
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: Cd. Madero
country: Mexico
facility: Local Institution
state: Tamaulipas
city: Aguascalientes
country: Mexico
facility: Local Institution
city: Chihuahua
country: Mexico
facility: Local Institution
city: Gjettum
country: Norway
facility: Local Institution
city: Kongsvinger
country: Norway
facility: Local Institution
city: Lillehammer
country: Norway
facility: Local Institution
city: Tonsberg
country: Norway
facility: Local Institution
city: Tynset
country: Norway
facility: Local Institution
city: Gdansk
country: Poland
facility: Local Institution
city: Lodz
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: Wroclaw
country: Poland
facility: Local Institution
city: Bucharest
country: Romania
facility: Local Institution
city: Cluj Napoca
country: Romania
facility: Local Institution
city: Chelyabinsk
country: Russian Federation
facility: Local Institution
city: Kazan
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Saint Petersburg
country: Russian Federation
facility: Local Institution
city: Saint Petersburg
country: Russian Federation
facility: Local Institution
city: Saint Petersburg
country: Russian Federation
facility: Local Institution
city: Saint Petersburg
country: Russian Federation
facility: Local Institution
city: Saint Petersburg
country: Russian Federation
facility: Local Institution
city: Samara
country: Russian Federation
facility: Local Institution
city: St.Petersburg
country: Russian Federation
facility: Local Institution
city: Yaroslavl
country: Russian Federation
facility: Local Institution
city: Badalona-Barcelone
country: Spain
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Gothenburg
country: Sweden
facility: Local Institution
city: Stockholm
country: Sweden
facility: Local Institution
city: Cherkassy
country: Ukraine
facility: Local Institution
city: Chernivtsy
country: Ukraine
facility: Local Institution
city: Dnipropetrovsk
country: Ukraine
facility: Local Institution
city: Ivano-Frankivsk
country: Ukraine
facility: Local Institution
city: Kyiv
country: Ukraine
facility: Local Institution
city: Kyiv
country: Ukraine
facility: Local Institution
city: Sevastopol
country: Ukraine
facility: Local Institution
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
city: Wigan
country: United Kingdom
facility: Local Institution
state: Lancashire
city: Epsom
country: United Kingdom
facility: Local Institution
state: Surrey
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: Pineo GF, Gallus AS, Raskob GE, Chen D, Ramirez LM, Ramacciotti E, Lassen MR, Wang L. Apixaban after hip or knee arthroplasty versus enoxaparin: efficacy and safety in key clinical subgroups. J Thromb Haemost. 2013 Mar;11(3):444-51. doi: 10.1111/jth.12109.
citation: Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM; ADVANCE-3 Investigators. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med. 2010 Dec 23;363(26):2487-98. doi: 10.1056/NEJMoa1006885.