Study of an Investigational Drug for the Prevention of Thrombosis-related Events Following Hip Replacement Surgery (ADVANCE-3)
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)
1 other identifier
interventional
5,407
21 countries
143
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Mar 2007
Typical duration for phase_3
143 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 17, 2007
CompletedFirst Posted
Study publicly available on registry
January 18, 2007
CompletedStudy Start
First participant enrolled
March 1, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2009
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2009
CompletedResults Posted
Study results publicly available
May 14, 2014
CompletedMay 14, 2014
April 1, 2014
2.5 years
January 17, 2007
April 14, 2014
April 14, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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
Event rate=Number of events divided by the number of patients evaluated. A mandatory bilateral ascending contrast venogram was to be obtained on Day 35 (± 3). Patients with confirmed symptomatic DVT at any time, or asymptomatic DVT upon venography, were to receive treatment for DVT according to the investigator's standard of care. Signs and symptoms suggestive of VTE included, but were not limited to: 1) lower extremity DVT: erythema, warmth, pain, swelling, tenderness; and 2) PE: pleuritic chest pain, dyspnea, cough, hemoptysis, syncope, light-headedness/dizziness, tachypnea, and tachycardia. Intended Treatment Period started on day of randomization and, for patients who received treatment, ended at the later of 2 days after last dose of study drug or 38 days after the first dose (presurgery) of study drug. For randomized patients who did not receive study drug, the period ended 38 days after randomization.
Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose
Secondary Outcomes (13)
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
Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose
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
Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose
Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), Major or CRNM, and Any Bleeding During the Treatment Period
First dose of study drug (presurgery) through 2 days after the last dose of study drug
Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), and Death as Outcome
First dose of study drug (presurgery) through 30 days after the last dose of study drug
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period
First dose of study drug (presurgery) through 2 days after the last dose of study drug
- +8 more secondary outcomes
Study Arms (2)
Apixaban, 2.5 mg BID plus placebo
ACTIVE COMPARATORParticipants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
Enoxaparin, 40 mg QD plus placebo
EXPERIMENTALParticipants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
Interventions
Subcutaneous, 40 mg, once daily, 5 weeks
Oral tablets, 2.5 mg, twice daily, 5weeks
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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)
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (143)
Capstone Clinical Trials, Inc
Birmingham, Alabama, 35209, United States
West Alabama Research, Llc
Birmingham, Alabama, 35209, United States
Martin Bowen Hefley Orthopedics
Little Rock, Arkansas, 72205, United States
Orthoarkansas, P.A.
Little Rock, Arkansas, 72205, United States
Uc Davis Medical Center
Sacramento, California, 95817, United States
Colorado Orthopedic Consultants, Pc
Aurora, Colorado, 80012, United States
Advanced Orthopedic And Sports Medicine Specilists
Denver, Colorado, 80230, United States
Denver-Vail Orthopedics, P.C.
Denver, Colorado, 80230, United States
Pab Clinical Research
Brandon, Florida, 33511, United States
Research Alliance, Inc.
Clearwater, Florida, 33756, United States
Shrock Orthopedic Research
Fort Lauderdale, Florida, 33316, United States
Phoenix Clinical Research, Llc
Tamarac, Florida, 33321, United States
Atlanta Knee And Sports Medicine
Decatur, Georgia, 30033, United States
Americana Orthopedics
Boise, Idaho, 83702, United States
Bosie Orthopedic Clinic
Meridian, Idaho, 83642, United States
University Orthopedic Center
Altoona, Pennsylvania, 16602, United States
Gill Orthopedic Center
Lubbock, Texas, 79410, United States
Robert R. King, Md
Lubbock, Texas, 79410, United States
Unlimited Research
San Antonio, Texas, 78217, United States
Local Institution
Capital Federal, Buenos Aires, C1199ACK, Argentina
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Capital Federal, Buenos Aires, C1280AEB, Argentina
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Capital Federal, Buenos Aires, C1425AGP, Argentina
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Ciudad de Buenos Aires, Buenos Aires, C1426BOS, Argentina
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Coronel SuĂ¡rez, Buenos Aires, B7540GHD, Argentina
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Monte Grande, Buenos Aires, B1842DID, Argentina
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Camperdown, New South Wales, 2050, Australia
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Kogarah, New South Wales, 2217, Australia
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Lismore, New South Wales, 2480, Australia
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Southport, Queensland, 4215, Australia
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Bedford Park, South Australia, 5042, Australia
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Box Hill, Victoria, 3128, Australia
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Malvern, Victoria, 3144, Australia
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Windsor, Victoria, 3181, Australia
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Perth, Western Australia, 6000, Australia
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Antwerp, 2020, Belgium
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Brasschaat, 2930, Belgium
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Genk, 3600, Belgium
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Hasselt, 3500, Belgium
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Leuven, 3000, Belgium
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Edmonton, Alberta, T6G 2B7, Canada
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Ajax, Ontario, L1S 2J5, Canada
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Cambridge, Ontario, N1R 7L7, Canada
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Chatham, Ontario, N7L 4T1, Canada
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Guelph, Ontario, N1E 6L9, Canada
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Newmarket, Ontario, L3Y 5G8, Canada
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Oshawa, Ontario, L1J 2J2, Canada
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Sarnia, Ontario, N7T 6H3, Canada
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Scarborough Village, Ontario, M1S 4T7, Canada
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St. Catharines, Ontario, L2R 7P3, Canada
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Stratford, Ontario, N5A 2N4, Canada
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Waterloo, Ontario, N2J 1C4, Canada
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Windsor, Ontario, N8W 1E6, Canada
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Montreal, Quebec, H3G 1A4, Canada
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Québec, Quebec, G1L 3L5, Canada
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Beijing, Beijing Municipality, 100035, China
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Beijing, Beijing Municipality, 100853, China
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Guangzhou, Guangdong, 510405, China
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Qingdao, Shandong, 266003, China
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Shanghai, Shanghai Municipality, 200011, China
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Shanghai, Shanghai Municipality, 200025, China
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Shanghai, Shanghai Municipality, 200233, China
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Amager, 2300, Denmark
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Frederiksberg, 2000, Denmark
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Herlev, 2730, Denmark
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Hvidovre, 2650, Denmark
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Hørsholm, 2970, Denmark
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København NV, 2400, Denmark
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Silkeborg, 8600, Denmark
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Nice, 06200, France
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Paris, 75014, France
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Paris, 75019, France
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Paris, 75679, France
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Saint-Etienne, 42100, France
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Saint-Saulve, 59880, France
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Frankfurt, 60528, Germany
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Frankfurt am Main, 65929, Germany
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Rheinfelden, 79618, Germany
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Budapest, 1081, Hungary
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Kecskemét, 6000, Hungary
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Szeged, 6720, Hungary
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Szolnok, 5000, Hungary
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Ahmedabad, Gujarat, 380015, India
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Ludhiana, Punjab, 141001, India
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Lucknow, Uttar Prsdesh, 226003, India
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Bangalore, 560034, India
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Mangalore, 575001, India
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Beersheba, 84101, Israel
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Haifa, 31096, Israel
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Holon, 58100, Israel
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Kfar Saba, 44281, Israel
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Ẕerifin, 70300, Israel
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Aguascalientes, Aguascalientes, 20010, Mexico
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Chihuahua City, Chihuahua, 31020, Mexico
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Tijuana, Estado de Baja California, 22010, Mexico
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Guadalajara, Jalisco, 45235, Mexico
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Mexico City, Mexico City, 06726, Mexico
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Mexico City, Mexico City, 07760, Mexico
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Monterrey, Nuevo LeĂ³n, 64460, Mexico
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Ciudad Madero, Tamaulipas, 89240, Mexico
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Gjettum, 1346, Norway
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Kongsvinger, 2212, Norway
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Lillehammer, 2629, Norway
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Tynset, 2500, Norway
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Tønsberg, 3116, Norway
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Gdansk, 80-803, Poland
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Lodz, 91-002, Poland
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Szczecin, 71-252, Poland
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Warsaw, 02-005, Poland
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Warsaw, 03-242, Poland
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Wroclaw, 50-556, Poland
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Bucharest, 021659, Romania
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Cluj-Napoca, 400132, Romania
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Chelyabinsk, 454021, Russia
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Kazan', 420029, Russia
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Moscow, 111539, Russia
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Moscow, 115522, Russia
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Moscow, 117292, Russia
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Moscow, 119415, Russia
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Saint Petersburg, 192242, Russia
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Saint Petersburg, 193312, Russia
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Saint Petersburg, 194354, Russia
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Saint Petersburg, 195427, Russia
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Saint Petersburg, 196247, Russia
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Saint Petersburg, 199106, Russia
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Samara, 443095, Russia
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Yaroslavl, 150003, Russia
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Badalona-Barcelone, 08916, Spain
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Barcelona, 08006, Spain
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Barcelona, 08024, Spain
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Barcelona, 08035, Spain
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Barcelona, 08036, Spain
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Gothenburg, 416 85, Sweden
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Stockholm, 182 88, Sweden
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Cherkassy, 18009, Ukraine
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Chernivtsy, 58013, Ukraine
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Dnipropetrovsk, 49005, Ukraine
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Ivano-Frankivsk, 76008, Ukraine
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Kyiv, 01601, Ukraine
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Kyiv, 04107, Ukraine
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Sevastopol, 99018, Ukraine
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London, Greater London, SE5 9RS, United Kingdom
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Wigan, Lancashire, WN6 9EP, United Kingdom
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Epsom, Surrey, KT18 7EG, United Kingdom
Related Publications (3)
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.
PMID: 35570249DERIVEDPineo 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.
PMID: 23279103DERIVEDLassen 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.
PMID: 21175312DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Bristol-Myers Squibb Study Director
- Organization
- Bristol-Myers Squibb
Study Officials
- STUDY DIRECTOR
Bristol-Myers Squibb
Bristol-Myers Squibb
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 17, 2007
First Posted
January 18, 2007
Study Start
March 1, 2007
Primary Completion
September 1, 2009
Study Completion
September 1, 2009
Last Updated
May 14, 2014
Results First Posted
May 14, 2014
Record last verified: 2014-04