A Phase 3 Randomized, Double-blind, Parallel-group, Multi-center Study of the Safetyand Efficacy of Apixaban for Prophylaxis of Venous Thromboembolism in Acutely IllMedical Subjects During and Following Hospitalization.ADOPT: Apixaban Dosing to Optimize Protection from ThrombosisAnd Pharmacogenetics Blood Sample Amendment 01 - Site Specific (Version 2.0, Date 27-Feb-2007)Revised Protocol Number 01 incorporating Amendment 02 and Admin Letter 01 (Version 5.0, dated 25-Jan-2008Protocol Amendment 03 dated 26-Feb-2009Revised Protocol 02 incorporating Amendment 04 version 7.0 dated 26-Feb-2009 - ADOPT

Conditions: Total Venous thromboembolism (VTE), defined as the combination of fatal or nonfatal pulmonary embolism, symptomatic deep vein thrombosis (DVT), and asymptomatic proximal DVT.
MedDRA version: 9.1Level: LLTClassification code 10051055Term: Deep vein thrombosis
MedDRA version: 9.1Level: LLTClassification code 10037377Term: Pulmonary embolism
MedDRA version: 9.1Level: LLTClassification code 10049918Term: Deep venous thrombosis proximal

Registration Number: EUCTR2006-003674-96-HU

Lead Sponsor: Bristol Myers Squibb

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 7502

Inclusion Criteria

1) Subjects must be willing and able to give written informed consent. Consent to participate in the study must be obtained prior to screening.
2) Subjects hospitalized due to congestive heart failure, acute respiratory failure or with infection (without septic shock), acute rheumatic disorder, or inflammatory bowel
disease.
3) Except for subjects with congestive heart failure or respiratory failure, subjects must have one additional factor including:
a) age = 75
b) previous documented VTE or history of VTE for which they received anticoagulation for at least 6 weeks
c) cancer
d) BMI = 30 (See Appendix 4 for BMI chart)
e) estrogenic hormone therapy
f) chronic heart or respiratory failure
4) Expected hospitalization of = 3 days after randomization
5) Severely or moderately restricted mobility (i.e. bedridden or limited to chair, walking to bathroom or within room; see section 6.9.1)
6) Men and women, of any race, at least 40 years of age

Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of investigational product.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) WOCBP who are unwilling or unable to use an acceptable method to avoid
pregnancy for the entire study period
2) WOCBP using a prohibited contraceptive method
3) Women who are pregnant or breastfeeding
4) Women with a positive pregnancy test on enrollment or prior to investigational
product administration
5) Subjects with a confirmed VTE
6) Subjects with diseases requiring ongoing treatment with a parenteral or oral
anticoagulant, e.g. subjects with mechanical valves, warfarin eligible atrial fibrillation
7) Subjects with conditions requiring ongoing treatment with parenteral or two or more oral antiplatelet agents
8) Active liver disease as evidenced by abnormal laboratory test findings (see physical and laboratory findings below)
9) Anemia or thrombocytopenia as evidenced by abnormal laboratory test findings (see physical and laboratory findings below)
10) Severe renal disease as evidenced by creatinine clearance < 30 mL/min as estimated by the method of Cockcroft and Gault (see Section 6.3.1.2)
11) Subjects hospitalized more than 72 hours prior to randomization
12) Subjects who are unable to take oral medications
13) Subjects who have had surgery in the past 30 days that may be associated with a risk of bleeding
14) Subjects who in the past 14 days have received treatment over consecutive days with: more than three doses of enoxaparin or another low molecular weight heparin; more than three doses of fondaparinux; more than six doses of unfractionated heparin; an infusion of unfractionated heparin for more than 72 hours; or more than two doses of an oral anticoagulant.
15) Subjects with active bleeding or high risk of bleeding
16) Subjects with planned or scheduled invasive procedures during the treatment period
17) Subjects in whom in the opinion of the Investigator it is not possible to obtain an
adequate bilateral compression ultrasound evaluation
18) Subjects with acute shock
19) Subjects with a life expectancy < 1 month
20) Abnormal hematological findings:
• Hemoglobin < 9 g/dL
• Platelet count < 100,000/mm3
21) Abnormal liver function tests:
• ALT or AST > 3 X ULN or
• ALT or AST > 2 X ULN without identification of an alternative causative factor or
• bilirubin (direct or total) > 1.5 X ULN (unless in an alternative causative factor
[e.g., Gilbert’s syndrome] is identified)
22) Known or suspected allergies to enoxaparin or prior heparin-induced
thrombocytopenia
23) Use of bevacizumab (Avastin®) therapy within the previous 6 months or planned use during the study period
24) Presently receiving oral anticoagulant therapy
25) Presently receiving dual oral antiplatelet therapy or aspirin at a dose > 165 mg.
26) Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg, infectious disease) illness must not be enrolled into this study
27) Administration of any investigational drug currently or within 30 days prior to
planned enrollment into this study
28) Subjects unwilling or unable to comply with study medication instructions including the use of enoxaparin or matching placebo for the minimum treatment duration of 6 days
29) Subjects unwilling or unable to comply with study procedures (e.g., bilateral
compression ultrasound) specified in the protocol
30) Subjects who have previously been randomized in an experimental study of apixaban