Study of Apixaban for the Prevention of Thrombosis-related Events in Patients With Acute Medical Illness

Pulmonary Embolism Clinical Trial

— ADOPT  

Official title:

A Phase 3 Randomized, Double-Blind, Parallel-group, Multi-center Study of the Safety and Efficacy of Apixaban for Prophylaxis of Venous Thromboembolism in Acutely Ill Medical Subjects During and Following Hospitalization.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00457002
• Other study ID #: CV185-036
• Status: Completed
• Phase: Phase 3
• First received: April 4, 2007
• Last updated: December 7, 2015
• Start date: June 2007
• Est. completion date: May 2011

Study information

• Verified date: May 2014
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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 within patients hospitalized for acute medical illness, and to learn how apixaban compares to enoxaparin (Lovenox®) for preventing these clots. The safety of apixaban will also be studied.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6758
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• men and non-pregnant, non-breastfeeding women

• 40 years or older

• hospitalized with congestive heart failure or acute respiratory failure

• infection (without septic shock)

• acute rheumatic disorder

• inflammatory bowel disease

Exclusion Criteria:

• patients with venous thromboembolism (VTE)

• active bleeding or at high risk of bleeding

• unable to take oral medication

• with diseases requiring ongoing treatment with anticoagulants or antiplatelets other than aspirin at a dose = 165 mg/day.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Embolism
• Pulmonary Embolism
• Thrombosis
• Venous Thrombosis

Intervention

Drug:
• Apixaban
Apixaban: Twice daily, 30 days Placebo: Once daily, 6-14 days
• Enoxaparin
Enoxaparin: Once daily, 6-14 days Placebo: Twice daily, 30 days

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Ciudad Autonoma Buenos Aires	Buenos Aires
Argentina	Local Institution	Cordoba
Argentina	Local Institution	Cordoba
Argentina	Local Institution	Coronel Suarez	Buenos Aires
Argentina	Local Institution	Corrientes
Argentina	Local Institution	Derqui-Pilar	Buenos Aires
Argentina	Local Institution	La Plata	Buenos Aires
Argentina	Local Institution	Munro	Buenos Aires
Argentina	Local Institution	Rosario	Santa Fe
Argentina	Local Institution	Rosario	Santa Fe
Argentina	Local Institution	San Martin	Buenos Aires
Argentina	Local Institution	San Miguel De Tucuman	Tucuman
Australia	Local Institution	Bedford Park	South Australia
Australia	Local Institution	Box Hill	Victoria
Australia	Local Institution	Concord	New South Wales
Australia	Local Institution	Kippa Ring	Queensland
Australia	Local Institution	Parkville	Victoria
Australia	Local Institution	Ringwood East	Victoria
Australia	Local Institution	St Leonards	New South Wales
Australia	Local Institution	Woodville	South Australia
Australia	Local Institution	Woolloongabba	Queensland
Austria	Local Institution	Graz
Austria	Local Institution	Wien
Belgium	Local Institution	Antwerpen
Belgium	Local Institution	Brasschaat
Belgium	Local Institution	Bruxelles
Belgium	Local Institution	Huy
Belgium	Local Institution	Leuven
Belgium	Local Institution	Ottignies	Waals-Brabant
Brazil	Local Institution	Belo Horizonte	Minas Gerais
Brazil	Local Institution	Botucatu	Sao Paulo
Brazil	Local Institution	Campinas	Sao Paulo
Brazil	Local Institution	Curitiba	Parana
Brazil	Local Institution	Curitiba	Parana
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Sao Jose Do Rio Preto	Sao Paulo
Brazil	Local Institution	Sao Paulo
Brazil	Local Institution	Sao Paulo
Brazil	Local Institution	Sao Paulo
Brazil	Local Institution	Sao Paulo
Canada	Local Institution	Ajax	Ontario
Canada	Local Institution	Granby	Quebec
Canada	Local Institution	Greenfield Park	Quebec
Canada	Local Institution	Hamilton	Ontario
Canada	Local Institution	Hamilton	Ontario
Canada	Local Institution	Montreal	Quebec
Canada	Local Institution	Montreal	Quebec
Canada	Local Institution	Montreal	Quebec
Canada	Local Institution	Windsor	Ontario
Canada	Local Institution	Windsor	Ontario
Chile	Local Institution	Rancagua	Valparaiso
Chile	Local Institution	Santiago	Metropolitana
Chile	Local Institution	Santiago	Metropolitana
Chile	Local Institution	Temuco	Araucania
Colombia	Local Institution	Bogota
Colombia	Local Institution	Bucaramanga
Colombia	Local Institution	Medellin
Czech Republic	Local Institution	Brno
Czech Republic	Local Institution	Jindrichuv Hradec
Czech Republic	Local Institution	Kladno
Czech Republic	Local Institution	Kyjov
Czech Republic	Local Institution	Ostrava
Czech Republic	Local Institution	Prague 2
Czech Republic	Local Institution	Praha 1
Czech Republic	Local Institution	Praha 5
Czech Republic	Local Institution	Usti Nad Labem
Denmark	Local Institution	Aalborg
Denmark	Local Institution	Aarhus N
Denmark	Local Institution	Arhus C
Denmark	Local Institution	Frederiksberg
Denmark	Local Institution	Glostrup
Denmark	Local Institution	Hellerup
Denmark	Local Institution	Herlev
Denmark	Local Institution	Herning
Denmark	Local Institution	Hvidovre
Denmark	Local Institution	Odense
Denmark	Local Institution	Randers No
Denmark	Local Institution	Silkeborg
France	Local Institution	Bordeaux
France	Local Institution	Brest
France	Local Institution	Brest Cedex
France	Local Institution	Dijon Cedex
France	Local Institution	Grenoble Cedex 9
France	Local Institution	Lille Cedex
France	Local Institution	Nancy
France	Local Institution	Nimes Cedex 9
France	Local Institution	Paris Cedex 10
France	Local Institution	Paris Cedex 15
France	Local Institution	Saint Etienne Cedex 02
France	Local Institution	Vernon
Germany	Local Institution	Bonn
Germany	Local Institution	Coburg
Germany	Local Institution	Darmstadt
Germany	Local Institution	Dresden
Germany	Local Institution	Dresden
Germany	Local Institution	Hannover
Germany	Local Institution	Karlsbad
Germany	Local Institution	Luebeck
Germany	Local Institution	Mannheim
Germany	Local Institution	Offenbach
Germany	Local Institution	Witten
Hong Kong	Local Institution	Shatin, N.T.
Hungary	Local Institution	Budapest
Hungary	Local Institution	Debrecen
Hungary	Local Institution	Dunaujvaros
Hungary	Local Institution	Eger
India	Local Institution	Ahemdabad	Gujarat
India	Local Institution	Ahmedabad
India	Local Institution	Bangalore
India	Local Institution	Bangalore
India	Local Institution	Bangalore	Karnataka
India	Local Institution	Chennai	Tamil-Nadu
India	Local Institution	Coimbatore	Tamil Nadu
India	Local Institution	Hyderabad	Andra Pradesh
India	Local Institution	Hyderabad
India	Local Institution	Indore	Madhya Pardesh
India	Local Institution	Ludhiana	Punjab
India	Local Institution	Madurai	Tamil Nadu
India	Local Institution	Mumbai
India	Local Institution	New Delhi
India	Local Institution	Noida	Uttar Pradesh
India	Local Institution	Pune	Maharashtra
India	Local Institution	Pune	Maharashtra
India	Local Institution	Pune	Maharastra
India	Local Institution	Vishakapatnam	Andhra-Pradesh
Israel	Local Institution	Afula
Israel	Local Institution	Ashkelon
Israel	Local Institution	Beer Sheva
Israel	Local Institution	Haifa
Israel	Local Institution	Petach Tikva
Israel	Local Institution	Safed
Israel	Local Institution	Tel Hashomer
Israel	Local Institution	Tel-Aviv
Israel	Local Institution	Zerifin
Italy	Local Institution	Chieti Scalo
Italy	Local Institution	Cremona
Italy	Local Institution	Padua
Italy	Local Institution	Piacenza
Italy	Local Institution	Reggio Emilia
Italy	Local Institution	Treviso
Italy	Local Institution	Vicenza
Korea, Republic of	Local Institution	Guri-Si	Gyeonggi-Do
Korea, Republic of	Local Institution	Seongnam-Si	Gyeonggi-Do
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Suwon
Malaysia	Local Institution	Batu Caves	Selangor
Malaysia	Local Institution	Johor Bahru
Malaysia	Local Institution	Kubang Kerian	Kelantan
Mexico	Local Institution	Merida	Yucatan
Mexico	Local Institution	Mexico	Distrito Federal
Mexico	Local Institution	Mexico	Distrito Federal
Mexico	Local Institution	Monterrey	Nuevo Leon
Mexico	Local Institution	Queretaro
Mexico	Local Institution	San Luis Potosi
Mexico	Local Institution	Xalapa	Veracruz
Netherlands	Local Institution	Den Helder
Norway	Local Institution	Kongsvinger
Peru	Local Institution	Arequipa
Peru	Local Institution	Callao
Peru	Local Institution	La Victoria	Lima
Peru	Local Institution	Lima
Peru	Local Institution	Lima
Peru	Local Institution	Lima
Peru	Local Institution	Lima
Philippines	Local Institution	Cagayan De Oro City	Misamis Oriental
Philippines	Local Institution	Las Pinas
Philippines	Local Institution	Quezon City
Philippines	Local Institution	Quezon City
Philippines	Local Institution	Quezon City
Poland	Local Institution	Bydgoszcz
Poland	Local Institution	Krakow
Poland	Local Institution	Lodz
Poland	Local Institution	Nowa Sol
Poland	Local Institution	Poznan
Poland	Local Institution	Skierniewice
Poland	Local Institution	Warszawa
Poland	Local Institution	Warszawa
Poland	Local Institution	Wejherowo
Poland	Local Institution	Zielona Gora
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Odintsovo
Russian Federation	Local Institution	Podolsk
Russian Federation	Local Institution	Ryazan
Russian Federation	Local Institution	Saint Petersburg
Russian Federation	Local Institution	Saint-Petersburg
Russian Federation	Local Institution	Saratov
Russian Federation	Local Institution	Saratov
Russian Federation	Local Institution	St Petersburg
Russian Federation	Local Institution	St. Petersburg
Russian Federation	Local Institution	St.Petersburg
Singapore	Local Institution	Singapore
Singapore	Local Institution	Singapore
South Africa	Local Institution	Amanzimtoti	Kwa Zulu Natal
South Africa	Local Institution	Bellville	Western Cape
South Africa	Local Institution	Bloemfontein	Free State
South Africa	Local Institution	Groenkloof
South Africa	Local Institution	Johannesburg	Gauteng
South Africa	Local Institution	Pretoria	Gauteng
Spain	Local Institution	Alcorcon(Madrid)
Spain	Local Institution	Barcelona
Spain	Local Institution	Barcelona
Spain	Local Institution	Madrid
Spain	Local Institution	Madrid
Spain	Local Institution	Madrid
Spain	Local Institution	Madrid
Spain	Local Institution	Madrid
Spain	Local Institution	Sevilla
Spain	Local Institution	Tarragona
Spain	Local Institution	Torrevieja	Alicante
Sweden	Local Institution	Goteborg
Sweden	Local Institution	Lund
Taiwan	Local Institution	Taichung
Taiwan	Local Institution	Yung-Kang City	Tainan
Turkey	Local Institution	Ankara	Dikimevi
Turkey	Local Institution	Istanbul
Turkey	Local Institution	Istanbul	Capa
Ukraine	Local Institution	Donetsk
Ukraine	Local Institution	Kharkiv
Ukraine	Local Institution	Kharkiv
Ukraine	Local Institution	Kharkov
Ukraine	Local Institution	Kyiv
Ukraine	Local Institution	Kyiv
Ukraine	Local Institution	Kyiv
Ukraine	Local Institution	Kyiv
Ukraine	Local Institution	Kyiv
Ukraine	Local Institution	Kyiv
Ukraine	Local Institution	Kyiv
Ukraine	Local Institution	Lutsk
Ukraine	Local Institution	Lviv
Ukraine	Local Institution	Uzhgorod
Ukraine	Local Institution	Vinnitsa
United Kingdom	Local Institution	Dudley	West Midlands
United Kingdom	Local Institution	Hull	Yorkshire
United Kingdom	Local Institution	London	Greater London
United Kingdom	Local Institution	London	Greater London
United Kingdom	Local Institution	Newcastle	Tyne And Wear
United Kingdom	Local Institution	Uxbridge	Middlesex
United States	Lehigh Valley Hospital	Allentown	Pennsylvania
United States	Mission Hospital, Inc	Asheville	North Carolina
United States	Atlanta Institute For Medical Research, Inc	Atlanta	Georgia
United States	Pulmonary & Critical Care Of Atlanta	Atlanta	Georgia
United States	Franklin Square Hospital	Baltimore	Maryland
United States	Johns Hopkins University School Of Medicine	Baltimore	Maryland
United States	University Of Alabama At Birmingham Hospital	Birmingham	Alabama
United States	Mercury Street Medical Group, Pllc	Butte	Montana
United States	Infectious Disease Of Indiana Psc	Carmel	Indiana
United States	Florida Hospital Celebration Health	Celebration	Florida
United States	Research Alliance, Inc.	Clearwater	Florida
United States	University Of Missouri-Columbia	Columbia	Missouri
United States	Texas Health Presbyterian Dallas	Dallas	Texas
United States	Henry Ford Hospital, Transplant Institute	Detriot	Michigan
United States	Fort Smith Lung Center	Fort Smith	Arkansas
United States	The Milton S Hershey Medical Center Of Penn. State Univ.	Hershey	Pennsylvania
United States	Michael E. De Bakey Veteran Affairs Medical Center	Houston	Texas
United States	Heart Center Research, Llc	Huntsville	Alabama
United States	Idaho Falls Infectious Diseases, Pllc	Idaho Falls	Idaho
United States	Jacksonville Center For Clinical Research	Jacksonville	Florida
United States	Scripps Clinic/Scripps Health And Green Hospital	La Jolla	California
United States	Va Long Beach Healthcare System	Long Beach	California
United States	Univ. Of Southern Calif. /Norris Comprehensive Cancer Center	Los Angeles	California
United States	North Shore University Hospital	Manhasset	New York
United States	Morristown Memorial Hospital	Mornstown	New Jersey
United States	Intermountain Medical Center	Murray	Utah
United States	Yale University School Of Medicine	New Haven	Connecticut
United States	Norwalk Hospital	Norwalk	Connecticut
United States	West Suburban Hospital	Oak Park	Illinois
United States	Dr. Felt Medical Office	Oakland	California
United States	South Oklahoma Heart Research	Oklahoma City	Oklahoma
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Palmetto Nephrology Pa	Orangeburg	South Carolina
United States	Pensacola Lung Group	Pensacola	Florida
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Arizona Pulmonary Specialists, Ltd.	Phoenix	Arizona
United States	Mcguire Va Medical Center	Richmond	Virginia
United States	University Of Utah Medical Center	Salt Lake City	Utah
United States	Sonterra Clinical Research	San Antonio	Texas
United States	Sonterra Clinical Research	San Antonio	Texas
United States	Az Pulmonary Specialists Ltd	Scottsdale	Arizona
United States	Louisiana State University Health Sciences Center-Shreveport	Shreveport	Louisiana
United States	S. Carolina Pharmaceutical Research	Spartanburg	South Carolina
United States	Stanford University	Stanford	California
United States	Staten Island University Hospital	Staten Island	New York
United States	Cotton-O-Neil Clinical Research Center	Topeka	Kansas
United States	Indian River Med. Ctr.	Vero Beach	Florida
United States	George Washington University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  Colombia,  Czech Republic,  Denmark,  France,  Germany,  Hong Kong,  Hungary,  India,  Israel,  Italy,  Korea, Republic of,  Malaysia,  Mexico,  Netherlands,  Norway,  Peru,  Philippines,  Poland,  Russian Federation,  Singapore,  South Africa,  Spain,  Sweden,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Composite of Adjudicated Total Venous Thromboembolism (VTE) and VTE-related Death During the Intended Treatment Period - Primary Efficacy Population	VTE: nonfatal pulmonary embolism (PE), symptomatic deep vein thrombosis (DVT), or asymptomatic proximal DVT detected by ultrasound. VTE-related death: fatal PE or sudden death for which VTE could not be excluded as a cause. Intended Treatment Period=period that started on day of randomization: period ended (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; period ended (for not treated) 32 days after randomization. A bilateral compression ultrasound (CUS) was performed between Days 5 and 14 for detection of asymptomatic proximal DVT unless a symptomatic VTE was confirmed prior. CUS was also performed on Day 30 ± 2 except for those participants who had a confirmed symptomatic VTE or proximal asymptomatic DVT prior to that time. All efficacy events were adjudicated by the Independent Central Adjudication Committee (ICAC). Event rate (%): n/N*100 (n=number with observation; N=total efficacy evaluable participants).	Intended Treatment Period	No
Primary	Incidence of Major Bleeding During the Treatment Period in Treated Participants	Major bleeding was adjudicated by an ICAC using criteria from the International Society on Thrombosis and Hemostasis (ISTH) and was defined as acute clinically overt bleeding: associated with a fall in hemoglobin of 2 grams per deciliter (g/dL) or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 milliliters (mL) or more of whole blood, or bleeding in a critical site or bleeding which is fatal. Incidence determined by Event Rate (%): n/N*100 (n=number with observation; N=total efficacy evaluable participants).	Day 1, first dose of study drug, to last dose of study drug plus 2 days	Yes
Primary	Incidence of Clinically Relevant Non-Major (CRNM) Bleeding During the Treatment Period in Treated Participants	Bleeding was adjudicated by an ICAC using criteria from the ISTH. CRNM bleeding: acute clinically overt bleeding compromising hemodynamics; leading to hospitalization; traumatic subcutaneous hematoma; intramuscular hematoma; epistaxis that lasted for more than 5 minutes, was repetitive or led to an intervention; spontaneous gingival bleeding; spontaneous hematuria; macroscopic gastrointestinal hemorrhage (including at least 1 episode of melena or hematemesis, if clinically apparent with positive results on a fecal occult-blood test); rectal blood loss. Treatment Period=includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drugs for bleeding endpoints. Incidence determined by Event Rate (%): n/N*100 (n=number with observation; N=total efficacy evaluable participants).	Day 1, first dose of study drug, to last dose of study drug plus 2 days	Yes
Primary	Incidence of Composite of Major or Clinically Relevant Non-Major (CRNM) Bleeding During the Treatment Period in Treated Participants	Bleeding was adjudicated by an ICAC using criteria from the ISTH. Major bleeding: acute clinically overt bleeding: associated with a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 mL or more of whole blood, or bleeding in a critical site or bleeding which is fatal. CRNM bleeding: acute clinically overt bleeding compromising hemodynamics; leading to hospitalization; traumatic subcutaneous hematoma; intramuscular hematoma; epistaxis that lasted for more than 5 minutes, was repetitive or led to an intervention; spontaneous gingival bleeding; spontaneous hematuria; macroscopic gastrointestinal hemorrhage; rectal blood loss. Treatment Period=onset from first dose of study drug through 2 days after last dose of study drugs. Incidence: Event Rate (%): n/N*100 (n=number with observation; N=total efficacy evaluable participants).	Day 1, first dose of study drug, to last dose of study drug plus 2 days	Yes
Primary	Incidence of All Bleeding During the Treatment Period in Treated Participants	Bleeding was adjudicated by an ICAC using criteria from the ISTH. Treatment Period=includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drugs, for bleeding endpoints. Incidence determined by Event Rate (%): n/N*100 (n=number with observation; N=total efficacy evaluable participants).	Day 1, first dose of drug to last dose of drug plus 2 days	Yes
Secondary	Incidence of Adjudicated Total VTE and VTE-Related Death During Parenteral Treatment in Key Secondary Efficacy Evaluable Participants	Parenteral study drug=active or placebo enoxaparin. Parenteral treatment: started on the first dose of parenteral study drug and ended the day after the last dose of parenteral study drug. Key Secondary Efficacy population: all who received at least 1 dose of parenteral study drug and: (those without suspected VTE events during Parenteral Treatment) had an adjudicated evaluable ultrasound performed at the end of Parenteral Treatment; or (those with suspected VTE events during Parenteral Treatment) had those suspected VTE events adjudicated as non-events, and had an adjudicated evaluable ultrasound performed at the end of Parenteral Treatment; or had an adjudicated total VTE during Parenteral Treatment; or had an adjudicated VTE-related death during Parenteral Treatment. Event rate (%): n/N*100 (n=number with observation; N=total secondary efficacy evaluable participants).	Day 1 to last dose of parenteral study drug plus 1 day	No
Secondary	Incidence of Adjudicated Total VTE and VTE-Related Death During Parenteral Treatment in Secondary Efficacy Evaluable Participants	Parenteral study drug=active or placebo enoxaparin. Parenteral treatment: started on the first dose of parenteral study drug and ended the day after the last dose of parenteral study drug. Secondary Efficacy Evaluable includes those who had an adjudicated, evaluable ultrasound at end of parenteral treatment and for those with a suspected symptomatic event, the result of the adjudication for the symptomatic event was not inadequate; or those with an adjudicated event that was part of the composite endpoint.. Event rate (%): n/N*100 (n=number with observation; N=total secondary efficacy evaluable participants).	Day 1 to last dose of parenteral study drug plus 1 day	No
Secondary	Incidence of Adjudicated Total VTE or All-Cause Death With Onset During the Intended Treatment Period	Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE: nonfatal (N-F) PE, symptomatic DVT, or asymptomatic proximal DVT detected by ultrasound. VTE-related death: fatal PE or sudden death for which VTE cannot be excluded as a cause. All-Cause Death (A-C Death). Incidence determined by Event Rate (%): n/N*100 (n=number with observation; N=total efficacy evaluable participants).	Intended Treatment Period	Yes
Secondary	Incidence of Adjudicated Proximal DVT, Non-Fatal PE or All-Cause Death With Onset During the Intended Treatment Period	Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. Incidence determined by Event Rate (%): n/N*100 (n=number with observation; N=total efficacy evaluable participants).	Intended Treatment Period	No
Secondary	Incidence of Adjudicated Proximal DVT, Non-Fatal PE or VTE-Related Death, With Onset During the Intended Treatment Period	Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE-related death: fatal PE or sudden death for which VTE cannot be excluded as a cause. Incidence determined by Event Rate (%): n/N*100 (n=number with observation; N=total efficacy evaluable participants).	Intended Treatment Period	No
Secondary	Incidence of Adjudicated VTE-Related Death With Onset During the Intended Treatment Period in Randomized Participants	Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE-related death: fatal PE or sudden death for which VTE cannot be excluded as a cause. Incidence determined by Event Rate (%): n/N*100 (n=number with observation; N=total efficacy evaluable participants).	Intended Treatment Period	No
Secondary	Incidence of Adjudicated Symptomatic VTE or All-Cause Death With Onset During the Intended Treatment Period	Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE: nonfatal PE, symptomatic DVT, or asymptomatic proximal DVT detected by ultrasound. Incidence determined by Event Rate (%): n/N*100 (n=number with observation; N=total efficacy evaluable participants).	Intended Treatment Period	No
Secondary	Symptomatic Adjudicated VTE or VTE-Related Death With Onset During the Intended Treatment Period	Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE: nonfatal PE, symptomatic DVT, or asymptomatic proximal DVT detected by ultrasound. VTE-related death: fatal PE or sudden death for which VTE cannot be excluded as a cause. Incidence determined by Event Rate (%): n/N*100 (n=number with observation; N=total efficacy evaluable participants).	Intended Treatment Period	No
Secondary	Incidence of All VTE or Major Bleeding or All-Cause Death During the Intended Treatment Period	Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE: nonfatal PE, symptomatic DVT, or asymptomatic proximal DVT detected by ultrasound. VTE-related death: fatal PE or sudden death for which VTE cannot be excluded as a cause. Incidence determined by Event Rate (%): n/N*100 (n=number with observation; N=total efficacy evaluable participants).	Intended Treatment Period	No
Secondary	Incidence of Adjudicated PE With Onset During the Intended Treatment Period	Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. PE: non-fatal or fatal. Incidence determined by Event Rate (%): n/N*100 (n=number with observation; N=total efficacy evaluable participants).	Intended Treatment Period	No
Secondary	Incidence of Adjudicated Non-Fatal PE With Onset During the Intended Treatment Period	Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. Incidence determined by Event Rate (%): n/N*100 (n=number with observation; N=total efficacy evaluable participants).	Intended Treatment Period	No
Secondary	Incidence of Adjudicated Symptomatic DVT With Onset During the Intended Treatment Period	Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. Incidence determined by Event Rate (%): n/N*100 (n=number with observation; N=total efficacy evaluable participants).	Intended Treatment Period	No
Secondary	Incidence of Adjudicated Proximal DVT With Onset During the Intended Treatment Period	Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. A bilateral compression ultrasound (CUS) was performed between Days 5 and 14 for detection of asymptomatic proximal DVT unless a symptomatic VTE was confirmed prior. CUS was also performed on Day 30 ± 2 except for those participants who had a confirmed symptomatic VTE or proximal asymptomatic DVT prior to that time. Incidence determined by Event Rate (%): n/N*100 (n=number with observation; N=total efficacy evaluable participants).	Intended Treatment Period	No
Secondary	Incidence of Adjudicated Symptomatic Distal DVT With Onset During the Intended Treatment Period	Events were adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. Incidence determined by Event Rate (%): n/N*100 (n=number with observation; N=total efficacy evaluable participants).	Intended Treatment Period	No
Secondary	Incidence of Adjudicated Symptomatic Proximal DVT With Onset During the Intended Treatment Period	Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. A bilateral compression ultrasound (CUS) was performed between Days 5 and 14 for detection of asymptomatic proximal DVT unless a symptomatic VTE was confirmed prior. CUS was also performed on Day 30 ± 2 except for those participants who had a confirmed symptomatic VTE or proximal asymptomatic DVT prior to that time. Incidence determined by Event Rate (%): n/N*100 (n=number with observation; N=total efficacy evaluable participants).	Intended Treatment Period	No
Secondary	Incidence of Adjudicated Asymptomatic Proximal DVT With Onset During the Intended Treatment Period	A bilateral compression ultrasound (CUS) was performed between Days 5 and 14 for detection of asymptomatic proximal DVT unless a symptomatic VTE was confirmed prior. CUS was also performed on Day 30 ± 2 except for those participants who had a confirmed symptomatic VTE or proximal asymptomatic DVT prior to that time. Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. Incidence determined by Event Rate (%): n/N*100 (n=number with observation; N=total efficacy evaluable participants).	Intended Treatment Period	No
Secondary	Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Deaths, and Discontinuations Due to AEs During the Treatment Period in Treated Participants	Treatment Period=includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drugs for AEs, and 30 days after last dose of study drugs for SAEs and deaths.	Day 1, first dose of study drug, to last dose of study drug plus 2 days (AEs), plus 30 days (SAEs, Deaths)	Yes
Secondary	Mean Change From Baseline in Diastolic Blood Pressure in Treated Participants During Treatment Period	Diastolic blood pressure was obtained during Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days. Blood pressure was measured in millimeters of mercury (mmHg) and could have been taken with the participant either sitting, standing, or supine.	Day 1 to last dose of study drug plus 2 days	Yes
Secondary	Mean Change From Baseline in Systolic Blood Pressure in Treated Participants During Treatment Period	Systolic blood pressure was obtained during Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days. Blood pressure was measured in millimeters of mercury (mmHg) and could have been taken either sitting, standing, or supine.	Day 1 to last dose of study drug plus 2 days	Yes
Secondary	Mean Change From Baseline in Heart Rate in Treated Participants	Heart Rate was obtained during Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days. Heart rate was measured in beats per minute (bpm) and could have been taken with participants either sitting, standing, or supine.	Day 1 to last dose of study drug plus 2 days	Yes
Secondary	Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants	Lower limit of normal (LLN). Upper limit of normal (ULN). Pre-therapy (PreRx). Absolute (Abs) neutrophil count, bands + neutrophils (ANC). Cells per microliter (c/µL). Grams per deciliter (g/dL). Cells per Liter (c/L). Millimeter (MM). Absolute (Abs). Hemoglobin: >2 g/dL decrease compared to PreRx value or value <=8 g/dL; Hematocrit: <0.75*PreRx; Erythrocytes: <0.75*PreRx c/µL; Leukocytes: <0.75*LLN or > 1.25*ULN, if PreRx	Day 1 to last dose of study drug plus 2 days	Yes
Secondary	Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants	Bicarbonate milliequivalents/Liter (mEq/L) Low/High: < 0.75*LLN or > 1.25*ULN, or if PreRx < LLN then use < 0.75* PreRx or > ULN if PreRx > ULN then use > 1.25*PreRx or < LLN; Serum Calcium mg/dL Low/High: < 0.8*LLN or > 1.2*ULN, or if PreRx < LLN then use < 0.75*PreRx or > ULN if PreRx > ULN then use > 1.25*PreRx or < LLN; Serum Chloride mEq/L: < 0.9*LLN or > 1.1*ULN, or if PreRx < LLN then use < 0.9*PreRx or > ULN if PreRx > ULN then use > 1.1*PreRx or < LLN; Serum Potassium mEq/L: < 0.9*LLN or > 1.1*ULN, or if PreRx < LLN then use < 0.9*PreRx or > ULN if PreRx > ULN then use > 1.1*PreRx or < LLN; Serum Sodium mEq/L: < 0.95*LLN or > 1.05*ULN, or if PreRx < LLN then use < 0.95*PreRx or > ULN if PreRx > ULN then use > 1.05*PreRx or < LLN. Samples obtained at Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days.	Day 1 to last dose of study drug plus 2 days	Yes
Secondary	Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants	Blood urea nitrogen (BUN), milligrams/deciliter (mg/dL), units per liter (U/L). BUN mg/dL > 1.5*ULN; Creatinine mg/dL: > 1.5*ULN; Alanine aminotransferase (ALT) U/L: > 3*ULN; Aspartate aminotransferase (AST) U/L: > 3*ULN; Alkaline phosphatase U/L: > 2*ULN; Bilirubin Direct mg/dL: > 1.5*ULN; Bilirubin Total mg/dL: > 2*ULN. Samples for laboratories obtained at Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days.	Day 1 to last dose of study drug plus 2 days	Yes
Secondary	Number of Participants With Marked Abnormalities in Glucose, Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests During the Treatment Period in Treated Participants	Creatine kinase High: >5*ULN Units/Liter (U/L); Total Protein High/Low: < 0.9 *LLN or > 1.1*ULN, or if PreRx < LLN then use 0.9* PreRx or > ULN if PreRx > ULN then use 1.1 *PreRx or	Day 1 to last dose of study drug plus 2 days	Yes
Secondary	Incidence of Events of Special Interest of Adjudicated Myocardial Infarction, Stroke, and Thrombocytopenia During the Treatment Period in Treated Participants	Events of Special Interest include: adjudicated thrombocytopenia, adjudicated myocardial infarction (MI), adjudicated stroke, and adjudicated MI or stroke. Incidence determined by Event Rate (%): n/N*100 (n=number with observation; N=total efficacy evaluable participants). Treatment Period includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drugs.	Day 1 to last dose of study drug plus 2 days	Yes
Secondary	Number of Participants With Events of Special Interest for Liver Function and Neurology During Treatment Period in Treated Participants With Available Measurements	Special interest include: liver function test increases, AEs related to liver function, and neurologic AEs. Treatment Period includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drug when summarizing AEs and through 30 days after the last dose when summarizing SAEs.	Day 1 to last dose of study drug plus 2 days (AEs) and plus 30 days (SAEs)	Yes
Secondary	Number of Participants With Liver-Related Elevations During the Treatment Period in Treated Participants	Liver function tests: Alanine aminotransferase (ALT) U/L; Aspartate aminotransferase (AST) U/L; Alkaline phosphatase U/L; Total Bilirubin (TBili) mg/dL. Elevations consist of >3*Upper Limit of Normal (ULN) for ALT and AST and elevation of >2*ULN for Bilirubin.	Day 1 to last dose of study drug plus 2 days	Yes

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form