Study of Apixaban for the Prevention of Thrombosis-related Events Following Knee Replacement Surgery

NCT00371683 | Completed Phase 3 Results DMC

• 1 other identifier: CV185-034
• Study Type: interventional
• Target: 3,608
• Locations: 13 countries
• Sites: 107

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.

Conditions

Deep Vein Thrombosis; Pulmonary Embolism

Keywords

Prevention of deep vein thrombosis and pulmonary embolism after total knee replacement surgery

Outcome Measures

Primary Outcomes (3)

• Event Rate of the Composite of Adjudicated Venous Thromboembolism (VTE) Events and All-Cause Death With Onset During the Intended Treatment Period - Primary Subjects

  An Independent Central Adjudication Committee (ICAC) adjudicated all venograms, suspected symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE), acute clinically overt bleeding events, suspected thrombocytopenia, suspected acute MI, suspected acute stroke, and cause of death. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed and reported as percentage (%). Surgery=Day 1; Randomization/Treatment started on Day of Surgery or the next day (Day 1 or Day 2). A mandatory bilateral ascending contrast venogram was performed on all participants after 12 days (±2 days) of study treatment. Intended Treatment Period=starts on the day of randomization; for treated participants, the period ends at the latter of 2 days after last dose of study drug or 14 days after the first dose of study drug; for randomized participants who were not treated, the period ends 14 days after randomization.

  From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

• 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

  ICAC adjudicated acute clinically overt bleeding events as per International Society on Thrombosis and Hemostasis (ISTH) guidelines modified for surgical patients. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed (%). Clinically relevant (CR); Non-Major (N-M) Bleeding. Day 1=Day of surgery. Treatment started (first dose) day of surgery or next day. Treatment continued for 12 days.

  First dose of study drug to last dose, plus 2 days post last dose

• 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

  ICAC adjudicated acute clinically overt bleeding events as per International Society on Thrombosis and Hemostasis (ISTH) guidelines modified for surgical patients. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed (%). Follow up Period was from the end of the treatment period (last dose) up to 60 days post last dose, Day 72.

  Last dose of study drug to Day 72 (60 days)

Secondary Outcomes (21)

• 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

  From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

• Event Rate of Adjudicated VTE / VTE-related Death With Onset During the Treatment Period

  From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

• Event Rate for Participants With Proximal DVT/Non-Fatal PE/ VTE-Related Death With Onset During the Intended Treatment Period

  From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

• Event Rate for Total Participants With Adjudicated VTE/All-Cause Death With Onset During the Intended Treatment Period

  From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

• Event Rate for Total Participants With VTE/ VTE-Related Death With Onset During the Intended Treatment Period

  From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

Study Arms (2)

A1

ACTIVE COMPARATOR

\+ placebo

Drug: Enoxaparin + Placebo

A2

EXPERIMENTAL

\+ placebo

Drug: Apixaban + Placebo

Interventions

Enoxaparin + Placebo DRUG

Syringes + tablets, Subcutaneous + Oral, 30mg, twice daily, 12 day treatment period

Also known as: Lovenox®

A1

Apixaban + Placebo DRUG

Tablet + Syringes, Oral + subcutaneous, 2.5 mg, twice daily, 12 day treatment period

A2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (107)

Capstone Clinical Trials, Inc

Birmingham, Alabama, 35205, United States

Location

Capstone Clinical Trials, Inc

Birmingham, Alabama, 35209, United States

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West Alabama Research, Inc.

Tuscaloosa, Alabama, 35406, United States

Location

Martin Bowen Hefley Orthopedics

Little Rock, Arkansas, 72205, United States

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Colorado Orthopedic Consultants, Pc

Aurora, Colorado, 80012, United States

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Colorado Joint Replacement

Denver, Colorado, 80210, United States

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Jdpmedical Research

Denver, Colorado, 80230, United States

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Orhtopaedic Physicians Of Colorado, P.C.

Englewood, Colorado, 80113, United States

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Orthopedics Assocs Of Hartford

Hartford, Connecticut, 06106, United States

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Anthony S. Unger, Md

Washington D.C., District of Columbia, 20006, United States

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Bay Pines Va Medical Center

Bay Pines, Florida, 33744, United States

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Pab Clinical Research

Brandon, Florida, 33511, United States

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Jacksonville Center For Clinical Research

Jacksonville, Florida, 32216, United States

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Mark W. Hollmann, Md

Orange City, Florida, 32763, United States

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Jewett Orthopaedic Clinic

Winter Park, Florida, 32789, United States

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Atlanta Knee And Sports Medicine

Decatur, Georgia, 30033, United States

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Americana Orthopedics

Boise, Idaho, 83702, United States

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Intermountain Orthopaedics

Boise, Idaho, 83702, United States

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Bluegrass Orthopaedics/Bmr

Lexington, Kentucky, 40509, United States

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Charleston Orthopaedic Assocs.

Charleston, South Carolina, 29414, United States

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Kelsey Seybold Clinic

Houston, Texas, 77025, United States

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Bone & Joint Clinic Of Houston

Houston, Texas, 77030, United States

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Gill Orthopedic Center

Lubbock, Texas, 79410, United States

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Robert R. King, Md

Lubbock, Texas, 79410, United States

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Unlimited Research

San Antonio, Texas, 78217, United States

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Local Institution

Buenos Aires, Buenos Aires, 1280, Argentina

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Buenos Aires, Buenos Aires, 1425, Argentina

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Buenos Aires, Buenos Aires, 7540, Argentina

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Buenos Aires, Buenos Aires, C1181, Argentina

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Capital Federal, Buenos Aires, 1012, Argentina

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Capital Federal, Buenos Aires, 1426, Argentina

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Córdoba, Córdoba Province, 5000, Argentina

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Garran, Australian Capital Territory, 2605, Australia

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Camperdown, New South Wales, NSW 2050, Australia

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Caringbah, New South Wales, 2229, Australia

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Lismore, New South Wales, 2480, Australia

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Gold Coast, Queensland, 4215, Australia

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Adelaide, South Australia, 5011, Australia

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Bedford Park, South Australia, 5042, Australia

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Box Hill, Victoria, 3128, Australia

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Windsor, Victoria, 3181, Australia

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Perth, Western Australia, 6001, Australia

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Curitiba, Paraná, 80060, Brazil

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Porto Alegre, Rio Grande do Sul, 90035, Brazil

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Porto Alegre, Rs, Rio Grande do Sul, 90020, Brazil

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Campinas, São Paulo, 13083, Brazil

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São Paulo, São Paulo, 05403, Brazil

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Edmonton, Alberta, T6G 2R7, Canada

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Ajax, Ontario, L1S 2J5, Canada

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Burlington, Ontario, L7R 4B7, Canada

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Cambridge, Ontario, N1R 7L7, Canada

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Chatham, Ontario, N7L 4T1, Canada

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Dartmouth, Ontario, B2Y 2N6, Canada

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Guelph, Ontario, N1E 6L9, Canada

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Lindsay, Ontario, K9V 4M8, Canada

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Newmarket, Ontario, L3Y 5G8, Canada

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Niagara Falls, Ontario, L2E 6X2, Canada

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Sarnia, Ontario, N7T 6H3, Canada

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Scarborough Village, Ontario, M1S 4T7, Canada

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Scarborough Village, Ontario, M3C 1W3, 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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Charlottetown, Prince Edward Island, C1A 1L2, Canada

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Montreal, Quebec, H4J 1C5, Canada

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Québec, Quebec, G1L 3L5, Canada

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Hørsholm, 2970, Denmark

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Kopenhamn S, 2300, Denmark

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Kecskemét, 6000, Hungary

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Székesfehérvár, 8000, Hungary

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Szolnok, 5008, Hungary

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Afula, 18101, Israel

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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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Petah Tikva, 49100, Israel

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Rehovot, 76100, Israel

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Ẕerifin, 70300, Israel

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Chihuahua City, Chihuahua, 31000, Mexico

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Tijuana, Estado de Baja California, 22010, Mexico

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Guadalajara, Jalisco, 44280, Mexico

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Df, Mexico City, 01030, Mexico

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Df, Mexico City, 05300, Mexico

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Df, Mexico City, 07760, Mexico

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Monterrey, Nuevo León, 64000, Mexico

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Monterrey, Nuevo León, 64460, Mexico

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Ciudad Madero, Tamaulipas, 89240, Mexico

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Jalapa, Veracruz, 91020, Mexico

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Mérida, Yucatán, 97070, Mexico

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Mérida, Yucatán, 97133, Mexico

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Bialystok, 15276, Poland

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Krakow, 31-826, Poland

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Lodz, 91002, Poland

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Lublin, 20954, Poland

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Szczecin, 71252, Poland

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Warsaw, 00909, Poland

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Warsaw, 02005, Poland

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Moscow, 117333, Russia

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Saint Petersburg, 195257, Russia

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Samara, 443095, Russia

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Gothenburg, 416 85, Sweden

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Adana, 01330, Turkey (Türkiye)

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Bursa, 16059, Turkey (Türkiye)

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Mersin, 33163, Turkey (Türkiye)

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Trabzon, 61030, Turkey (Türkiye)

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Related Publications (2)

• 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: 35570249 DERIVED

• 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.

  PMID: 19657123 DERIVED

MeSH Terms

Conditions

Venous Thrombosis; Pulmonary Embolism

Interventions

Enoxaparin; apixaban

Condition Hierarchy (Ancestors)

Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Embolism

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

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: August 30, 2006
• First Posted: September 4, 2006
• Study Start: November 1, 2006
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2008
• Last Updated: December 30, 2015
• Results First Posted: December 30, 2015

Record last verified: 2015-11

Locations

DK (2); AU (10); AR (7); HU (3); RU (3); IL (8); SE (1); BR (5); ME (12); PL (7); TU (4); CA (20); US (25)