Cancer, Pulmonary Embolism, Thrombosis
Conditions
Keywords
anticoagulant
Brief summary
The purpose of this study is to learn whether apixaban is well-tolerated and acceptable as anticoagulant therapy, when administered to patients with advanced or metastatic cancer and at increased risk for venous thromboembolic events. Demonstration of a favorable benefit:risk profile could lead to significant reduction in this serious and sometimes fatal complication of ongoing cancer and its treatment.
Interventions
DRUGApixaban
Oral tablets administered once daily in 5-, 10-, or 20-mg dose
DRUGPlacebo
Oral tablets administered once daily
Sponsors
Ontario Clinical Oncology Group (OCOG)
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Recipients of either first- or second-line chemotherapy for advanced or metastatic lung, breast, gastrointestinal, bladder, ovarian, or prostate cancer or myeloma, selected lymphomas, or cancer of unknown origin * Able to begin study medication ≤6 weeks of starting either first- or second-line chemotherapy. * Expected course of chemotherapy must have been ≥ 90 days after the start of chemotherapy * Per Protocol Amendment 5, patients receiving bevacizumab were eligible to participate, provided that bevacizumab was used for indications approved by local country law Key
Exclusion criteria
* Women who are pregnant, breastfeeding * History of deep vein thrombosis or pulmonary embolism * Active bleeding or at high risk of bleeding * Metastatic brain cancer * Familial bleeding diathesis * Serious hemorrhage requiring hospitalization, transfusion, or surgical intervention within 4 weeks of study entry * Expected survival \<6 months or an Eastern Cooperative Oncology Group performance status ≥3. * Candidates for bone marrow transplantation within the 12-week treatment period or 30-day follow-up period * Uncontrolled hypertension (systolic blood pressure \>200 mm Hg and/or diastolic blood pressure \>110 mm Hg * Coagulopathy (international normalized ratio \>1.5 or platelet count \<100\*10\^9/L) if not yet receiving chemotherapy or \<50\*10\^9/L if receiving chemotherapy). Platelet count must have been \>100\*10\^9/L before starting study medication * One or more of the following: alanine aminotransferase \>3 times the upper limit of normal (ULN), total bilirubin \>2\*ULN, or calculated creatinine clearance \<30 mL/min.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Composite of Confirmed Major Bleeding and Clinically Relevant Nonmajor (CRNM) Bleeding | From first dose to 2 days following last dose of study drug | Major bleeding was defined as clinically overt bleeding accompanied by 1 or more of the following: * A decrease in hemoglobin of 20 g/L or more or * Required transfusion of 2 or more units of packed red blood cells or whole blood, or * Occurred in a critical site * Contributed to death. CRNM bleeding was defined as bleeding that did not meet the criteria for major bleeding but that, in routine clinical practice, would be considered relevant and not trivial by a patient and physician. Such bleeding satisfied a priori criteria defined by the ICAC, including: * Skin hematoma * Epistaxis that lasted for longer than 5 minutes, was repetitive, or led to an intervention * Hematuria that was macroscopic and either spontaneous or lasted for longer than 24 hours after instrumentation of the urogenital tract * Any other bleeding type that was considered to have clinical consequences. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and All-cause Death | First dose to 30 days following last dose of study drug | Any 1 of the following was considered diagnostic for DVT: * New or previously undocumented noncompressibility of 1 or more proximal venous segments (popliteal vein or higher) of the legs on CUS * Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava. Any 1 of the following was considered diagnostic for PE: * Constant intraluminal filling defects in 2 or more views on pulmonary angiography * Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram * A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) * An abnormal VQ lung scan (nonhigh probability) with satisfaction of either criterion 1 or 2 * Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels. |
| Number of Participants With Composite of Venous Thromboembolism (VTE) and VTE-related Death | First dose to 2 days following last dose of study drug | VTE includes symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE). Any 1 of the following was considered diagnostic for DVT: * New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS * Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava. Any 1 of the following was considered diagnostic for PE: * Constant intraluminal filling defects in 2 or more views on pulmonary angiography * Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram * A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) * An abnormal VQ lung scan with satisfaction of either criterion 1 or 2 * Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels. |
| Number of Participants With Composite of Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and Venous Thromboembolism (VTE)-Related Death | First dose to 2 days following last dose of study drug | VTE includes symptomatic DVT and PE. Any 1 of the following was considered diagnostic for DVT: * New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS * Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava. Any 1 of the following was considered diagnostic for PE: * Constant intraluminal filling defects in 2 or more views on pulmonary angiography * Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram * A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) * An abnormal VQ lung scan with satisfaction of either criterion 1 or 2 * Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels. |
| Number of Participants With All-Cause Death | First dose to 2 days following last dose of study drug | — |
| Number of Participants With Pulmonary Embolism (Fatal or Nonfatal) | First dose to 2 days following last dose of study drug | Any 1 of the following was considered diagnostic for PE: * Constant intraluminal filling defects in 2 or more views on pulmonary angiography * Sudden contrast cutoff of 1 or more vessels of greater than 2.5 mm in diameter on a pulmonary angiogram * A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) * An abnormal VQ lung scan with satisfaction of either criterion 1 or 2 * Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels. |
| Number of Participants With Composite of Venous Thromboembolism (VTE) and All-cause Death | First dose to 2 days following last dose of study drug | VTE includes symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE). Any 1 of the following was considered diagnostic for DVT: * New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS * Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava. Any 1 of the following was considered diagnostic for PE: * Constant intraluminal filling defects in 2 or more views on pulmonary angiography * Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram * A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) * An abnormal VQ lung scan with satisfaction of either criterion 1 or 2 * Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels. |
| Number of Participants With Deep Vein Thrombosis | First dose to 2 days following last dose of study drug | Any 1 of the following was considered diagnostic for DVT: * New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS * Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava. |
| Number of Participants With Distal Deep Vein Thrombosis | First dose to 2 days following last dose of study drug | Any 1 of the following was considered diagnostic for DVT: * New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS * Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava. |
| Number of Participants With Proximal Deep Vein Thrombosis | First dose to 2 days following last dose of study drug | Any 1 of the following was considered diagnostic for DVT: * New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS * Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava. |
| Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | First dose to 2 days following last dose of study drug | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. |
| Number of Participants With Nonfatal Pulmonary Embolism | First dose to 2 days following last dose of study drug | Any 1 of the following was considered diagnostic for PE: * Constant intraluminal filling defects in 2 or more views on pulmonary angiography * Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram * A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) * An abnormal VQ lung scan with satisfaction of either criterion 1 or 2 * Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels. |
Countries
Canada, United States
Participant flow
Pre-assignment details
A total of 130 participants were enrolled and randomized; however, 1 withdrew consent and 2 no longer met study criteria. Therefore, 127 participants were treated. Reasons Not Completed listed in the data table below were summarized for 127 participants who received treatment.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Placebo Participants received placebo tablets once daily | 30 |
| Cohort 1: Apixaban, 5 mg Participants received apixaban as tablet, 5 mg, once daily | 32 |
| Cohort 1: Apixaban, 10 mg Participants received apixaban as tablet, 10 mg, once daily | 30 |
| Cohort 1: Apixaban, 20 mg Participants received apixaban as tablet, 20 mg, once daily | 33 |
| Cohort 2: Placebo Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received placebo once daily. | 2 |
| Cohort 2: Apixaban, 5 mg Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received apixaban as tablet, 5 mg, once daily. | 3 |
| Total | 130 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 2 | 3 | 2 | 0 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | No longer meets study criteria | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Other | 3 | 2 | 1 | 0 | 0 | 0 |
| Overall Study | Poor compliance/noncompliance | 1 | 1 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 2 | 4 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1: Placebo | Total | Cohort 2: Apixaban, 5 mg | Cohort 2: Placebo | Cohort 1: Apixaban, 20 mg | Cohort 1: Apixaban, 10 mg | Cohort 1: Apixaban, 5 mg |
|---|---|---|---|---|---|---|---|
| Age, Customized 65 years and older but younger than 75 years | 8 Participants | 30 Participants | 0 Participants | 1 Participants | 8 Participants | 9 Participants | 4 Participants |
| Age, Customized 75 years and older | 5 Participants | 15 Participants | 0 Participants | 0 Participants | 8 Participants | 2 Participants | 0 Participants |
| Age, Customized Younger than 65 years | 17 Participants | 85 Participants | 3 Participants | 1 Participants | 17 Participants | 19 Participants | 28 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 7 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black/African American | 0 Participants | 6 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 6 Participants | 0 Participants | 0 Participants | 3 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 27 Participants | 110 Participants | 3 Participants | 2 Participants | 25 Participants | 26 Participants | 27 Participants |
| Sex: Female, Male Female | 15 Participants | 64 Participants | 2 Participants | 0 Participants | 13 Participants | 17 Participants | 17 Participants |
| Sex: Female, Male Male | 15 Participants | 66 Participants | 1 Participants | 2 Participants | 20 Participants | 13 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 24 / 29 | 28 / 32 | 24 / 29 | 30 / 32 | 2 / 2 | 3 / 3 |
| serious Total, serious adverse events | 9 / 29 | 6 / 32 | 3 / 29 | 5 / 32 | 1 / 2 | 0 / 3 |
Outcome results
Primary
Number of Participants With Composite of Confirmed Major Bleeding and Clinically Relevant Nonmajor (CRNM) Bleeding
Major bleeding was defined as clinically overt bleeding accompanied by 1 or more of the following: * A decrease in hemoglobin of 20 g/L or more or * Required transfusion of 2 or more units of packed red blood cells or whole blood, or * Occurred in a critical site * Contributed to death. CRNM bleeding was defined as bleeding that did not meet the criteria for major bleeding but that, in routine clinical practice, would be considered relevant and not trivial by a patient and physician. Such bleeding satisfied a priori criteria defined by the ICAC, including: * Skin hematoma * Epistaxis that lasted for longer than 5 minutes, was repetitive, or led to an intervention * Hematuria that was macroscopic and either spontaneous or lasted for longer than 24 hours after instrumentation of the urogenital tract * Any other bleeding type that was considered to have clinical consequences.
Time frame: From first dose to 2 days following last dose of study drug
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Placebo | Number of Participants With Composite of Confirmed Major Bleeding and Clinically Relevant Nonmajor (CRNM) Bleeding | 1 Participants |
| Cohort 1: Apixaban, 5 mg | Number of Participants With Composite of Confirmed Major Bleeding and Clinically Relevant Nonmajor (CRNM) Bleeding | 1 Participants |
| Cohort 1: Apixaban, 10 mg | Number of Participants With Composite of Confirmed Major Bleeding and Clinically Relevant Nonmajor (CRNM) Bleeding | 1 Participants |
| Cohort 1: Apixaban, 20 mg | Number of Participants With Composite of Confirmed Major Bleeding and Clinically Relevant Nonmajor (CRNM) Bleeding | 4 Participants |
| Cohort 2: Placebo | Number of Participants With Composite of Confirmed Major Bleeding and Clinically Relevant Nonmajor (CRNM) Bleeding | 2 Participants |
| Cohort 2: Apixaban, 5 mg | Number of Participants With Composite of Confirmed Major Bleeding and Clinically Relevant Nonmajor (CRNM) Bleeding | 3 Participants |
Secondary
Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Time frame: First dose to 2 days following last dose of study drug
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Placebo | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | Bleeding AEs | 6 Participants |
| Cohort 1: Placebo | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | SAEs | 9 Participants |
| Cohort 1: Placebo | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | Discontinuations due to AEs | 7 Participants |
| Cohort 1: Placebo | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | Deaths | 2 Participants |
| Cohort 1: Apixaban, 5 mg | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | Deaths | 1 Participants |
| Cohort 1: Apixaban, 5 mg | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | SAEs | 6 Participants |
| Cohort 1: Apixaban, 5 mg | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | Bleeding AEs | 15 Participants |
| Cohort 1: Apixaban, 5 mg | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | Discontinuations due to AEs | 4 Participants |
| Cohort 1: Apixaban, 10 mg | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | SAEs | 3 Participants |
| Cohort 1: Apixaban, 10 mg | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | Deaths | 0 Participants |
| Cohort 1: Apixaban, 10 mg | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | Bleeding AEs | 11 Participants |
| Cohort 1: Apixaban, 10 mg | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | Discontinuations due to AEs | 4 Participants |
| Cohort 1: Apixaban, 20 mg | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | SAEs | 5 Participants |
| Cohort 1: Apixaban, 20 mg | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | Bleeding AEs | 12 Participants |
| Cohort 1: Apixaban, 20 mg | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | Deaths | 0 Participants |
| Cohort 1: Apixaban, 20 mg | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | Discontinuations due to AEs | 4 Participants |
| Cohort 2: Placebo | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | Deaths | 0 Participants |
| Cohort 2: Placebo | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | SAEs | 1 Participants |
| Cohort 2: Placebo | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | Discontinuations due to AEs | 1 Participants |
| Cohort 2: Placebo | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | Bleeding AEs | 1 Participants |
| Cohort 2: Apixaban, 5 mg | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | Bleeding AEs | 2 Participants |
| Cohort 2: Apixaban, 5 mg | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | Discontinuations due to AEs | 0 Participants |
| Cohort 2: Apixaban, 5 mg | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | Deaths | 0 Participants |
| Cohort 2: Apixaban, 5 mg | Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs | SAEs | 0 Participants |
Secondary
Number of Participants With All-Cause Death
Time frame: First dose to 2 days following last dose of study drug
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Placebo | Number of Participants With All-Cause Death | 0 Participants |
| Cohort 1: Apixaban, 5 mg | Number of Participants With All-Cause Death | 0 Participants |
| Cohort 1: Apixaban, 10 mg | Number of Participants With All-Cause Death | 0 Participants |
| Cohort 1: Apixaban, 20 mg | Number of Participants With All-Cause Death | 0 Participants |
| Cohort 2: Placebo | Number of Participants With All-Cause Death | 0 Participants |
| Cohort 2: Apixaban, 5 mg | Number of Participants With All-Cause Death | 0 Participants |
Secondary
Number of Participants With Composite of Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and Venous Thromboembolism (VTE)-Related Death
VTE includes symptomatic DVT and PE. Any 1 of the following was considered diagnostic for DVT: * New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS * Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava. Any 1 of the following was considered diagnostic for PE: * Constant intraluminal filling defects in 2 or more views on pulmonary angiography * Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram * A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) * An abnormal VQ lung scan with satisfaction of either criterion 1 or 2 * Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.
Time frame: First dose to 2 days following last dose of study drug
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Placebo | Number of Participants With Composite of Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and Venous Thromboembolism (VTE)-Related Death | 3 Participants |
| Cohort 1: Apixaban, 5 mg | Number of Participants With Composite of Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and Venous Thromboembolism (VTE)-Related Death | 0 Participants |
| Cohort 1: Apixaban, 10 mg | Number of Participants With Composite of Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and Venous Thromboembolism (VTE)-Related Death | 0 Participants |
| Cohort 1: Apixaban, 20 mg | Number of Participants With Composite of Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and Venous Thromboembolism (VTE)-Related Death | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Composite of Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and Venous Thromboembolism (VTE)-Related Death | 0 Participants |
| Cohort 2: Apixaban, 5 mg | Number of Participants With Composite of Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and Venous Thromboembolism (VTE)-Related Death | 0 Participants |
Secondary
Number of Participants With Composite of Venous Thromboembolism (VTE) and All-cause Death
VTE includes symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE). Any 1 of the following was considered diagnostic for DVT: * New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS * Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava. Any 1 of the following was considered diagnostic for PE: * Constant intraluminal filling defects in 2 or more views on pulmonary angiography * Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram * A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) * An abnormal VQ lung scan with satisfaction of either criterion 1 or 2 * Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.
Time frame: First dose to 2 days following last dose of study drug
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Placebo | Number of Participants With Composite of Venous Thromboembolism (VTE) and All-cause Death | 4 Participants |
| Cohort 1: Apixaban, 5 mg | Number of Participants With Composite of Venous Thromboembolism (VTE) and All-cause Death | 0 Participants |
| Cohort 1: Apixaban, 10 mg | Number of Participants With Composite of Venous Thromboembolism (VTE) and All-cause Death | 0 Participants |
| Cohort 1: Apixaban, 20 mg | Number of Participants With Composite of Venous Thromboembolism (VTE) and All-cause Death | 1 Participants |
| Cohort 2: Placebo | Number of Participants With Composite of Venous Thromboembolism (VTE) and All-cause Death | 0 Participants |
| Cohort 2: Apixaban, 5 mg | Number of Participants With Composite of Venous Thromboembolism (VTE) and All-cause Death | 0 Participants |
Secondary
Number of Participants With Composite of Venous Thromboembolism (VTE) and VTE-related Death
VTE includes symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE). Any 1 of the following was considered diagnostic for DVT: * New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS * Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava. Any 1 of the following was considered diagnostic for PE: * Constant intraluminal filling defects in 2 or more views on pulmonary angiography * Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram * A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) * An abnormal VQ lung scan with satisfaction of either criterion 1 or 2 * Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.
Time frame: First dose to 2 days following last dose of study drug
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Placebo | Number of Participants With Composite of Venous Thromboembolism (VTE) and VTE-related Death | 4 Participants |
| Cohort 1: Apixaban, 5 mg | Number of Participants With Composite of Venous Thromboembolism (VTE) and VTE-related Death | 0 Participants |
| Cohort 1: Apixaban, 10 mg | Number of Participants With Composite of Venous Thromboembolism (VTE) and VTE-related Death | 0 Participants |
| Cohort 1: Apixaban, 20 mg | Number of Participants With Composite of Venous Thromboembolism (VTE) and VTE-related Death | 1 Participants |
| Cohort 2: Placebo | Number of Participants With Composite of Venous Thromboembolism (VTE) and VTE-related Death | 0 Participants |
| Cohort 2: Apixaban, 5 mg | Number of Participants With Composite of Venous Thromboembolism (VTE) and VTE-related Death | 0 Participants |
Secondary
Number of Participants With Deep Vein Thrombosis
Any 1 of the following was considered diagnostic for DVT: * New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS * Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava.
Time frame: First dose to 2 days following last dose of study drug
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Placebo | Number of Participants With Deep Vein Thrombosis | 4 Participants |
| Cohort 1: Apixaban, 5 mg | Number of Participants With Deep Vein Thrombosis | 0 Participants |
| Cohort 1: Apixaban, 10 mg | Number of Participants With Deep Vein Thrombosis | 0 Participants |
| Cohort 1: Apixaban, 20 mg | Number of Participants With Deep Vein Thrombosis | 1 Participants |
| Cohort 2: Placebo | Number of Participants With Deep Vein Thrombosis | 0 Participants |
| Cohort 2: Apixaban, 5 mg | Number of Participants With Deep Vein Thrombosis | 0 Participants |
Secondary
Number of Participants With Distal Deep Vein Thrombosis
Any 1 of the following was considered diagnostic for DVT: * New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS * Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava.
Time frame: First dose to 2 days following last dose of study drug
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Placebo | Number of Participants With Distal Deep Vein Thrombosis | 1 Participants |
| Cohort 1: Apixaban, 5 mg | Number of Participants With Distal Deep Vein Thrombosis | 0 Participants |
| Cohort 1: Apixaban, 10 mg | Number of Participants With Distal Deep Vein Thrombosis | 0 Participants |
| Cohort 1: Apixaban, 20 mg | Number of Participants With Distal Deep Vein Thrombosis | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Distal Deep Vein Thrombosis | 0 Participants |
| Cohort 2: Apixaban, 5 mg | Number of Participants With Distal Deep Vein Thrombosis | 0 Participants |
Secondary
Number of Participants With Nonfatal Pulmonary Embolism
Any 1 of the following was considered diagnostic for PE: * Constant intraluminal filling defects in 2 or more views on pulmonary angiography * Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram * A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) * An abnormal VQ lung scan with satisfaction of either criterion 1 or 2 * Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.
Time frame: First dose to 2 days following last dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Placebo | Number of Participants With Nonfatal Pulmonary Embolism | 1 Participants |
| Cohort 1: Apixaban, 5 mg | Number of Participants With Nonfatal Pulmonary Embolism | 0 Participants |
| Cohort 1: Apixaban, 10 mg | Number of Participants With Nonfatal Pulmonary Embolism | 0 Participants |
| Cohort 1: Apixaban, 20 mg | Number of Participants With Nonfatal Pulmonary Embolism | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Nonfatal Pulmonary Embolism | 0 Participants |
| Cohort 2: Apixaban, 5 mg | Number of Participants With Nonfatal Pulmonary Embolism | 0 Participants |
Secondary
Number of Participants With Proximal Deep Vein Thrombosis
Any 1 of the following was considered diagnostic for DVT: * New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS * Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava.
Time frame: First dose to 2 days following last dose of study drug
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Placebo | Number of Participants With Proximal Deep Vein Thrombosis | 3 Participants |
| Cohort 1: Apixaban, 5 mg | Number of Participants With Proximal Deep Vein Thrombosis | 0 Participants |
| Cohort 1: Apixaban, 10 mg | Number of Participants With Proximal Deep Vein Thrombosis | 0 Participants |
| Cohort 1: Apixaban, 20 mg | Number of Participants With Proximal Deep Vein Thrombosis | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Proximal Deep Vein Thrombosis | 0 Participants |
| Cohort 2: Apixaban, 5 mg | Number of Participants With Proximal Deep Vein Thrombosis | 0 Participants |
Secondary
Number of Participants With Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and All-cause Death
Any 1 of the following was considered diagnostic for DVT: * New or previously undocumented noncompressibility of 1 or more proximal venous segments (popliteal vein or higher) of the legs on CUS * Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava. Any 1 of the following was considered diagnostic for PE: * Constant intraluminal filling defects in 2 or more views on pulmonary angiography * Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram * A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) * An abnormal VQ lung scan (nonhigh probability) with satisfaction of either criterion 1 or 2 * Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.
Time frame: First dose to 30 days following last dose of study drug
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Placebo | Number of Participants With Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and All-cause Death | 3 Participants |
| Cohort 1: Apixaban, 5 mg | Number of Participants With Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and All-cause Death | 0 Participants |
| Cohort 1: Apixaban, 10 mg | Number of Participants With Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and All-cause Death | 0 Participants |
| Cohort 1: Apixaban, 20 mg | Number of Participants With Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and All-cause Death | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and All-cause Death | 0 Participants |
| Cohort 2: Apixaban, 5 mg | Number of Participants With Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and All-cause Death | 0 Participants |
Secondary
Number of Participants With Pulmonary Embolism (Fatal or Nonfatal)
Any 1 of the following was considered diagnostic for PE: * Constant intraluminal filling defects in 2 or more views on pulmonary angiography * Sudden contrast cutoff of 1 or more vessels of greater than 2.5 mm in diameter on a pulmonary angiogram * A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect) * An abnormal VQ lung scan with satisfaction of either criterion 1 or 2 * Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.
Time frame: First dose to 2 days following last dose of study drug
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Placebo | Number of Participants With Pulmonary Embolism (Fatal or Nonfatal) | 1 Participants |
| Cohort 1: Apixaban, 5 mg | Number of Participants With Pulmonary Embolism (Fatal or Nonfatal) | 0 Participants |
| Cohort 1: Apixaban, 10 mg | Number of Participants With Pulmonary Embolism (Fatal or Nonfatal) | 0 Participants |
| Cohort 1: Apixaban, 20 mg | Number of Participants With Pulmonary Embolism (Fatal or Nonfatal) | 0 Participants |
| Cohort 2: Placebo | Number of Participants With Pulmonary Embolism (Fatal or Nonfatal) | 0 Participants |
| Cohort 2: Apixaban, 5 mg | Number of Participants With Pulmonary Embolism (Fatal or Nonfatal) | 0 Participants |