Deep Vein Thrombosis, Pulmonary Embolism
Conditions
Keywords
Prevention of deep vein thrombosis and pulmonary embolism after total knee replacement surgery
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.
Interventions
DRUGEnoxaparin + Placebo
Syringes + tablets, Subcutaneous + Oral, 30mg, twice daily, 12 day treatment period
DRUGApixaban + Placebo
Tablet + Syringes, Oral + subcutaneous, 2.5 mg, twice daily, 12 day treatment period
Sponsors
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 No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Men and non-pregnant, non-breastfeeding women * 18 years or older * Scheduled for knee replacement surgery Key
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event Rate of the Composite of Adjudicated Venous Thromboembolism (VTE) Events and All-Cause Death With Onset During the Intended Treatment Period - Primary Subjects | From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization | 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. |
| 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 | First dose of study drug to last dose, plus 2 days post last dose | 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. |
| 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 | Last dose of study drug to Day 72 (60 days) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | ICAC adjudicated all venograms, suspected symptomatic DVT and PE, and cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%). |
| 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 | ICAC adjudicated all venograms, suspected symptomatic DVT and PE, and cause of death. VTE includes DVT and PE. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%). |
| Event Rate for Participants With 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 was number of participants with all-cause death divided by the number of participant's analyzed (%). |
| Event Rate for Participants With 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 | ICAC adjudicated cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%). |
| Event Rate for Participants With Symptomatic 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 | ICAC adjudicated suspected symptomatic DVT and PE, and cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%). |
| Event Rate for Participants With Symptomatic 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 | ICAC adjudicated suspected symptomatic DVT and PE, and cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%). |
| Event Rate for Participants With VTE/Major Bleeding/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 | ICAC adjudicated VTE, acute clinically overt bleeding events, suspected thrombocytopenia, and cause of death. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed (%). |
| Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period | From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization | An 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 (%). |
| Event Rate for Participants With Proximal DVT, Distal DVT, Asymptomatic Proximal DVT, Asymptomatic Distal DVT With Onset During the Intended Treatment Period | From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization | ICAC adjudicated all venograms and suspected symptomatic DVT. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%). |
| 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 | A mandatory bilateral ascending contrast venogram was performed on all participants after 12 days (±2 days) of study treatment. An ICAC adjudicated all venograms, suspected proximal DVT and non-fatal PE, and all-cause of death. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed and reported as percentage (%). |
| Event Rate of Adjudicated MI, Stroke, and Thrombocytopenia Events During the Follow-Up Period | Post last dose of study drug to Day 72 (60 days) | A 60-day follow-up period started after the last dose of study drug and continued until the End of Study Visit on Day 72 (60 days ± 3 days, after the last dose of study drug). Event rate was number of participants with the endpoint divided by the number of participants analyzed (%). ICAC adjudicated acute clinically overt bleeding events, suspected thrombocytopenia, suspected acute MI, suspected acute stroke per ISTH guidelines modified for surgical patients. |
| Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), AEs Leading to Discontinuation, and Deaths - Treated Population | First dose to last dose, plus 2 days for AEs (12 + 2 days) or plus 30 days for SAEs (12 + 30 days) | 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. |
| Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period | Baseline to last dose of study drug, plus 2 days | Treatment Period=the period from first dose of study drug through 2 days after discontinuation of study drug (12 + 2 days). Baseline=measurement prior to first dose of study drug. Blood pressures (BP) were measured during screening (pre-operative, post-operative) and in the treatment period on Days 1 (day of first dose), 2, 3, 4,12 (end of treatment). Systolic and diastolic pressures were measured in millimeters of mercury (mmHg). |
| Mean Change From Baseline in Heart Rate During the Treatment Period | Baseline to last dose of study drug, plus 2 days | Treatment Period=the period from first dose of study drug through 2 days after discontinuation of study drug (12 + 2 days). Baseline=measurement prior to first dose of study drug. Heart rate was measured during screening (pre-operative, post-operative) and in the treatment period on Days 1 (day of first dose), 2, 3, 4,12 (end of treatment). Heart rate was measured in beats per minute (bpm). |
| Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | First dose to last dose of study drug (12 days), plus 2 days | Treatment Period=the period from first dose of study drug through 2 days after discontinuation of study drug. Hematology profile was measured during screening (pre-operative, post-operative) and in the Treatment Period on Days 2, 3, 4, 12 (end of treatment). Upper limit of normal (ULN); lower limit of normal (LLN). Platelet Count low: \< 100,000/mm\^3 (or \< 100\*109 cells/L). Erythrocytes low: \< 0.75 \*pre-dose. Hemoglobin low: \> 2 g/dL decrease compared to pre-dose or Value ≤ 8 g/dL. Hematocrit low: \< 0.75\*pre-dose . Leukocytes: \< 0.75\*LLN or \> 1.25\* ULN, or if pre-dose \< LLN then use \< 0.8\*predose or \> ULN if pre-dose \> ULN then use \> 1.2\*predose or \< LLN. Lymphocytes (absolute): \< 0.750\*10\^3 cells/µL or \> 7.50\*10\^3 cells/ µL. Eosinophils (absolute) high: \> 0.750\*10\^3 cells/µL. Basophils(absolute) high: \> 400/mm\^3 (or \> 0.4\*103 cells/µL). Monocytes (absolute) high: \> 2000/mm\^3 (or \> 2\*103 cells/µL). Neutrophils(absolute) high: \< 1.0\*103 cells/µL. |
| Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period | First dose to last dose of study drug (12 days), plus 2 days | Treatment Period=the period from first dose of study drug through 2 days after discontinuation of study drug. Laboratory Chemistry profile was measured during screening (pre-operative, post-operative) and in the Treatment Period on Days 4, and 12 (end of treatment). Bilirubin (direct) high: \> 1.5\*ULN. Total bilirubin: : \> 2\*ULN, Alanine Aminotransferase (ALT) high: \> 3\*ULN. Alkaline Phosphatase (ALP): \> 2\*ULN. Aspartate Aminotransferase (AST): \> 3\*ULN. Creatinine: \> 1.5\*ULN. |
| Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period | First dose to last dose of study drug (12 days), plus 2 days | Laboratory Chemistry profile was measured during screening (pre-operative, post-operative) and in the Treatment Period on Days 4, and 12 (end of treatment). Potassium: \< 0.9\*LLN or \> 1.1\*ULN, or if pre-dose \< LLN then use \< 0.9\*predose or \> ULN if pre-dose \> ULN then use \> 1.1\*predose or \< LLN. Calcium: \< 0.8\*LLN or \> 1.2\*ULN, or if pre-dose \< LLN then use \< 0.75\*predose or \> ULN If pre-dose \> ULN then use \> 1.25\*predose or \< LLN. Chloride: \< 0.9\*LLN or \> 1.1\*ULN, or if pre-dose \< LLN then use \< 0.9\*predose or \> ULN if pre-dose \> ULN then use \> 1.1\*predose or \< LLN. Sodium: \< 0.95\*LLN or \> 1.05\*ULN, or if pre-dose \< LLN then use \< 0.95\*predose or \>ULN if pre-dose \> ULN then use \> 1.05\*predose or \< LLN. Bicarbonate: \< 0.75\*LLN or \> 1.25\*ULN, or if pre-dose \< LLN then use \< 0.75\*predose or \> ULN if pre-dose \> ULN then use \> 1.25\*predose or \< LLN. |
| Number of Participants With Other Chemistry Laboratory Marked Abnormalities During the Treatment Period | First dose to last dose of study drug (12 days), plus 2 days | Treatment Period=the period from first dose of study drug through 2 days after discontinuation of study drug. Laboratory Chemistry profile was measured during screening (pre-operative, post-operative) and in the Treatment Period on Days 4, and 12 (end of treatment). Fasting Glucose: if pre-dose \< LLN then use \< 0.8\*predose; or \> ULN if pre-dose \> ULN then use \> 2.0\*predose or \<LLN. Total Protein: \< 0.9\*LLN or \> 1.1\*ULN, or if pre-dose \< LLN then use 0.9\*predose or \> ULN if pre-dose \> ULN then use 1.1\*predose or \< LLN. Uric Acid: \> 1.5\*ULN, or if pre-dose \> ULN then use \> 2\*predose. Creatine Kinase (CK): \> 5\*ULN. |
| Event Rate for Participants With Adjudicated Myocardial Infarction (MI) Acute Ischemic Stroke and Thromboembolic Events With Onset During the Treatment Period | From first dose to last dose, plus 2 days (12 days, plus 2) | ICAC adjudicated acute clinically overt bleeding events, suspected thrombocytopenia, suspected acute MI, suspected acute stroke 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 (%). |
| 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 | VTE / VTE-related death was defined as the combination of fatal or non-fatal PE, and symptomatic or asymptomatic DVT. A mandatory bilateral ascending contrast venogram was performed on all participants after 12 days (±2 days) of study treatment. An ICAC adjudicated all venograms, suspected symptomatic DVT and PE, and cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%). |
| 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 | An ICAC adjudicated all venograms, suspected symptomatic DVT and PE, and cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%). |
Countries
Argentina, Australia, Brazil, Canada, Denmark, Hungary, Israel, Mexico, Poland, Russia, Sweden, Turkey (Türkiye), United States
Participant flow
Pre-assignment details
3608 patients enrolled and 3195 were randomized to double blind (DB) Treatment Period: 413 not randomized due to: 227 no longer met criteria, 109 withdrew consent, 60 other reasons, 11 administrative reason by sponsor, 5 adverse event, 1 poor, non-compliance.
Participants by arm
| Arm | Count |
|---|---|
| Apixaban 2.5mg BID Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, plus or minus 2 days. The study included a screening period that began no more than 30 days prior to surgery through 24 hours after surgery; a 12 (±2) day treatment period, starting on the day of the first dose of study drug; and a 60 (±3) day follow-up period, starting the day after the last dose of study drug (End of Treatment Period to Day 72). | 1,599 |
| Enoxaparin 30 mg SC Injection q 12 Hours Enoxaparin 30 mg subcutaneous (SC) injection every (q) 12 hours (h) plus matching placebo tablets BID for 12 days, plus or minus 2 days. The study included a screening period that began no more than 30 days prior to surgery through 24 hours after surgery; a 12 (±2) day treatment period, starting on the day of the first dose of study drug; and a 60 (±3) day follow-up period, starting the day after the last dose of study drug (End of Treatment Period to Day 72). | 1,596 |
| Total | 3,195 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| DB Treatment Period-Randomized Patients | Administrative reason by sponsor | 1 | 0 |
| DB Treatment Period-Randomized Patients | Adverse Event | 60 | 58 |
| DB Treatment Period-Randomized Patients | Death | 1 | 1 |
| DB Treatment Period-Randomized Patients | Lost to Follow-up | 0 | 1 |
| DB Treatment Period-Randomized Patients | No longer meets study criteria | 1 | 2 |
| DB Treatment Period-Randomized Patients | non-specified | 9 | 8 |
| DB Treatment Period-Randomized Patients | Withdrawal by Subject | 18 | 37 |
| Follow-Up Period - Randomized Patients | Death | 0 | 2 |
| Follow-Up Period - Randomized Patients | Lost to Follow-up | 38 | 39 |
| Follow-Up Period - Randomized Patients | non-specified | 6 | 12 |
| Follow-Up Period - Randomized Patients | Withdrawal by Subject | 17 | 19 |
Baseline characteristics
| Characteristic | Apixaban 2.5mg BID | Enoxaparin 30 mg SC Injection q 12 Hours | Total |
|---|---|---|---|
| Age, Continuous | 65.9 years STANDARD_DEVIATION 9.26 | 65.7 years STANDARD_DEVIATION 9.22 | 65.8 years STANDARD_DEVIATION 9.24 |
| Age, Customized >=75 years | 309 participants | 295 participants | 604 participants |
| Age, Customized Greater than, equal to (>=) 65 and < 75 years | 593 participants | 610 participants | 1203 participants |
| Age, Customized Less than(<) 65 years | 697 participants | 691 participants | 1388 participants |
| Region of Enrollment Argentina | 43 participants | 43 participants | 86 participants |
| Region of Enrollment Australia | 50 participants | 54 participants | 104 participants |
| Region of Enrollment Brazil | 42 participants | 39 participants | 81 participants |
| Region of Enrollment Canada | 554 participants | 548 participants | 1102 participants |
| Region of Enrollment Denmark | 87 participants | 89 participants | 176 participants |
| Region of Enrollment Hungary | 28 participants | 26 participants | 54 participants |
| Region of Enrollment Israel | 44 participants | 42 participants | 86 participants |
| Region of Enrollment Mexico | 138 participants | 138 participants | 276 participants |
| Region of Enrollment Norway | 21 participants | 17 participants | 38 participants |
| Region of Enrollment Poland | 35 participants | 35 participants | 70 participants |
| Region of Enrollment Russian Federation | 15 participants | 13 participants | 28 participants |
| Region of Enrollment Sweden | 66 participants | 68 participants | 134 participants |
| Region of Enrollment Turkey | 12 participants | 10 participants | 22 participants |
| Region of Enrollment United States | 464 participants | 474 participants | 938 participants |
| Sex: Female, Male Female | 997 Participants | 986 Participants | 1983 Participants |
| Sex: Female, Male Male | 602 Participants | 610 Participants | 1212 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 713 / 1,596 | 741 / 1,588 |
| serious Total, serious adverse events | 123 / 1,596 | 123 / 1,588 |
Outcome results
Primary
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.
Time frame: Last dose of study drug to Day 72 (60 days)
Population: All participants who received at least 1 dose of study drug during the Treatment Period and entered the Follow-Up Period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban 2.5mg BID | 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 | Major Bleeding (n=1563, 1553) | 0.13 percentage of participants |
| Apixaban 2.5mg BID | 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 | CR N-M Bleeding (n=1563, 1553) | 0.26 percentage of participants |
| Apixaban 2.5mg BID | 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 | Major or CR N-M Bleeding (n=1563, 1553) | 0.38 percentage of participants |
| Apixaban 2.5mg BID | 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 | Any Bleeding (n=1563, 1553) | 0.90 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | 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 | Any Bleeding (n=1563, 1553) | 1.29 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | 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 | Major Bleeding (n=1563, 1553) | 0.13 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | 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 | Major or CR N-M Bleeding (n=1563, 1553) | 0.58 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | 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 | CR N-M Bleeding (n=1563, 1553) | 0.45 percentage of participants |
Primary
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.
Time frame: First dose of study drug to last dose, plus 2 days post last dose
Population: All participants who received at least one dose of study drug (Treated population).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban 2.5mg BID | 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 | Major Bleeding (n=1596, 1588) | 0.69 percentage of participants |
| Apixaban 2.5mg BID | 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 | CR N-M Bleeding (n=1596, 1588) | 2.19 percentage of participants |
| Apixaban 2.5mg BID | 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 | Major or CR N-M Bleeding(n=1596, 1588) | 2.88 percentage of participants |
| Apixaban 2.5mg BID | 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 | Any Bleeding (n=1596, 1588) | 5.33 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | 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 | Any Bleeding (n=1596, 1588) | 6.80 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | 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 | Major Bleeding (n=1596, 1588) | 1.39 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | 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 | Major or CR N-M Bleeding(n=1596, 1588) | 4.28 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | 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 | CR N-M Bleeding (n=1596, 1588) | 2.96 percentage of participants |
Comparison: Adjusted difference of event rates of Major Bleeding. Type of surgery was taken into consideration as a stratification factor.95% CI: [-1.49, -0.14]
Comparison: Major Bleeding Endpointp-value: 0.0533test of equality
Comparison: Adjusted difference of event rates of Clinically Relevant Non-Major Bleeding. Type of surgery was taken into consideration as a stratification factor.95% CI: [-1.87, 0.33]
Comparison: Clinically relevant Non-Major Bleeding endpointp-value: 0.1709test of equality
Comparison: Adjusted difference of event rates of Major or Clinically Relevant Non-Major Bleeding. Type of surgery was taken into consideration as a stratification factor.95% CI: [-2.75, -0.17]
Comparison: Major or Clinically Relevant Non-Major Bleeding endpoint.p-value: 0.0338test of equality
Comparison: Adjusted difference of event rates of Any Bleeding. Type of surgery was taken into consideration as a stratification factor.95% CI: [-3.18, 0.13]
Comparison: Any Bleeding Endpoint.p-value: 0.0816test of equality
Primary
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.
Time frame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Population: Primary Population=All randomized participants who: have an adjudicated and evaluable bilateral venogram performed during the Intended Treatment Period; or have an adjudicated VTE during the Intended Treatment Period; or die due to any cause during the Intended Treatment Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5mg BID | Event Rate of the Composite of Adjudicated Venous Thromboembolism (VTE) Events and All-Cause Death With Onset During the Intended Treatment Period - Primary Subjects | 8.99 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate of the Composite of Adjudicated Venous Thromboembolism (VTE) Events and All-Cause Death With Onset During the Intended Treatment Period - Primary Subjects | 8.85 percentage of participants |
p-value: 0.063595% CI: [0.78, 1.32]t-test, 1 sided
p-value: <0.000195% CI: [-2.22, 2.44]t-test, 1 sided
Secondary
Event Rate for Participants With Adjudicated Myocardial Infarction (MI) Acute Ischemic Stroke and Thromboembolic Events With Onset During the Treatment Period
ICAC adjudicated acute clinically overt bleeding events, suspected thrombocytopenia, suspected acute MI, suspected acute stroke 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 (%).
Time frame: From first dose to last dose, plus 2 days (12 days, plus 2)
Population: All participants who received at least one dose of study drug were analyzed (Treated Population).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban 2.5mg BID | Event Rate for Participants With Adjudicated Myocardial Infarction (MI) Acute Ischemic Stroke and Thromboembolic Events With Onset During the Treatment Period | MI/Stroke | 0.06 percentage of participants |
| Apixaban 2.5mg BID | Event Rate for Participants With Adjudicated Myocardial Infarction (MI) Acute Ischemic Stroke and Thromboembolic Events With Onset During the Treatment Period | MI | 0.06 percentage of participants |
| Apixaban 2.5mg BID | Event Rate for Participants With Adjudicated Myocardial Infarction (MI) Acute Ischemic Stroke and Thromboembolic Events With Onset During the Treatment Period | Stroke | 0.00 percentage of participants |
| Apixaban 2.5mg BID | Event Rate for Participants With Adjudicated Myocardial Infarction (MI) Acute Ischemic Stroke and Thromboembolic Events With Onset During the Treatment Period | Thrombocytopenia | 0.00 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate for Participants With Adjudicated Myocardial Infarction (MI) Acute Ischemic Stroke and Thromboembolic Events With Onset During the Treatment Period | Thrombocytopenia | 0.13 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate for Participants With Adjudicated Myocardial Infarction (MI) Acute Ischemic Stroke and Thromboembolic Events With Onset During the Treatment Period | MI/Stroke | 0.31 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate for Participants With Adjudicated Myocardial Infarction (MI) Acute Ischemic Stroke and Thromboembolic Events With Onset During the Treatment Period | Stroke | 0.13 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate for Participants With Adjudicated Myocardial Infarction (MI) Acute Ischemic Stroke and Thromboembolic Events With Onset During the Treatment Period | MI | 0.25 percentage of participants |
Comparison: Adjusted difference of event rates of MI/Stroke. Type of surgery was taken into consideration as a stratification factor.95% CI: [-0.55, 0.05]
Comparison: Adjusted difference of event rates of MI. Type of surgery was taken into consideration as a stratification factor.95% CI: [-0.46, 0.09]
Comparison: Adjusted difference of event rates of Stroke. Type of surgery was taken into consideration as a stratification factor.95% CI: [-0.3, 0.05]
Comparison: Adjusted difference of event rates of thrombocytopenia. Type of surgery was taken into consideration as a stratification factor.95% CI: [-0.3, 0.05]
Secondary
Event Rate for Participants With All-Cause Death During the Intended Treatment Period
Event rate was number of participants with all-cause death divided by the number of participant's analyzed (%).
Time frame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Population: All Randomized participants were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5mg BID | Event Rate for Participants With All-Cause Death During the Intended Treatment Period | 0.19 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate for Participants With All-Cause Death During the Intended Treatment Period | 0.19 percentage of participants |
95% CI: [0.2, 4.93]
95% CI: [-0.3, 0.3]
p-value: 0.9975test of equality
Secondary
Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period
An 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 (%).
Time frame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Population: All randomized participants: PE, Symptomatic DVT, Symptomatic Proximal DVT, Symptomatic Distal DVT. Randomized with an adjudicated and evaluable bilateral venogram or an adjudicated event associated with the endpoint: All DVT, Asymptomatic DVT. n=number analyzed in each category
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban 2.5mg BID | Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period | All DVT n=1142, 1122 | 7.79 percentage of participants |
| Apixaban 2.5mg BID | Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period | Asymptomatic DVT (n=1139,1115) | 7.55 percentage of participants |
| Apixaban 2.5mg BID | Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period | Non-Fatal PE (n=1599, 1596) | 0.88 percentage of participants |
| Apixaban 2.5mg BID | Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period | Symptomatic Proximal DVT (n=1599,1596) | 0.13 percentage of participants |
| Apixaban 2.5mg BID | Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period | Symptomatic DVT (n=1599, 1596) | 0.19 percentage of participants |
| Apixaban 2.5mg BID | Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period | Symptomatic Distal DVT (n=1599,1596) | 0.06 percentage of participants |
| Apixaban 2.5mg BID | Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period | PE (Fatal or Non-Fatal) (n=1599, 1596) | 1.00 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period | Symptomatic Distal DVT (n=1599,1596) | 0.38 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period | PE (Fatal or Non-Fatal) (n=1599, 1596) | 0.44 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period | Non-Fatal PE (n=1599, 1596) | 0.44 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period | All DVT n=1142, 1122 | 8.20 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period | Symptomatic DVT (n=1599, 1596) | 0.44 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period | Asymptomatic DVT (n=1139,1115) | 7.62 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period | Symptomatic Proximal DVT (n=1599,1596) | 0.19 percentage of participants |
Secondary
Event Rate for Participants With Proximal DVT, Distal DVT, Asymptomatic Proximal DVT, Asymptomatic Distal DVT With Onset During the Intended Treatment Period
ICAC adjudicated all venograms and suspected symptomatic DVT. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).
Time frame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Population: Randomized participants with either an adjudicated and evaluable bilateral proximal (or distal, as appropriate) venogram or an adjudicated event associated with the endpoint. n= number analyzed
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban 2.5mg BID | Event Rate for Participants With Proximal DVT, Distal DVT, Asymptomatic Proximal DVT, Asymptomatic Distal DVT With Onset During the Intended Treatment Period | Proximal DVT (n=1254, 1207) | 0.72 percentage of participants |
| Apixaban 2.5mg BID | Event Rate for Participants With Proximal DVT, Distal DVT, Asymptomatic Proximal DVT, Asymptomatic Distal DVT With Onset During the Intended Treatment Period | Asymptomatic Proximal DVT (n=1252, 1204) | 0.56 percentage of participants |
| Apixaban 2.5mg BID | Event Rate for Participants With Proximal DVT, Distal DVT, Asymptomatic Proximal DVT, Asymptomatic Distal DVT With Onset During the Intended Treatment Period | Distal DVT (n=1146, 1133) | 7.24 percentage of participants |
| Apixaban 2.5mg BID | Event Rate for Participants With Proximal DVT, Distal DVT, Asymptomatic Proximal DVT, Asymptomatic Distal DVT With Onset During the Intended Treatment Period | Asymptomatic Distal DVT (n=1145, 1127) | 7.16 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate for Participants With Proximal DVT, Distal DVT, Asymptomatic Proximal DVT, Asymptomatic Distal DVT With Onset During the Intended Treatment Period | Distal DVT (n=1146, 1133) | 8.03 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate for Participants With Proximal DVT, Distal DVT, Asymptomatic Proximal DVT, Asymptomatic Distal DVT With Onset During the Intended Treatment Period | Proximal DVT (n=1254, 1207) | 0.91 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate for Participants With Proximal DVT, Distal DVT, Asymptomatic Proximal DVT, Asymptomatic Distal DVT With Onset During the Intended Treatment Period | Asymptomatic Distal DVT (n=1145, 1127) | 7.54 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate for Participants With Proximal DVT, Distal DVT, Asymptomatic Proximal DVT, Asymptomatic Distal DVT With Onset During the Intended Treatment Period | Asymptomatic Proximal DVT (n=1252, 1204) | 0.66 percentage of participants |
Secondary
Event Rate for Participants With Proximal DVT/Non-Fatal PE/ VTE-Related Death With Onset During the Intended Treatment Period
An ICAC adjudicated all venograms, suspected symptomatic DVT and PE, and cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).
Time frame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Population: Randomized participants with either an adjudicated and evaluable bilateral proximal venogram or an adjudicated event associated with the endpoint, during the Intended Treatment Period, were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5mg BID | Event Rate for Participants With Proximal DVT/Non-Fatal PE/ VTE-Related Death With Onset During the Intended Treatment Period | 1.97 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate for Participants With Proximal DVT/Non-Fatal PE/ VTE-Related Death With Onset During the Intended Treatment Period | 1.40 percentage of participants |
95% CI: [0.77, 2.6]
95% CI: [-0.47, 1.52]
p-value: 0.2626test of equality
Secondary
Event Rate for Participants With Symptomatic VTE/ All-Cause Death With Onset During the Intended Treatment Period
ICAC adjudicated suspected symptomatic DVT and PE, and cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).
Time frame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Population: All randomized participants were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5mg BID | Event Rate for Participants With Symptomatic VTE/ All-Cause Death With Onset During the Intended Treatment Period | 1.25 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate for Participants With Symptomatic VTE/ All-Cause Death With Onset During the Intended Treatment Period | 1.00 percentage of participants |
95% CI: [0.65, 2.4]
95% CI: [-0.47, 0.98]
Secondary
Event Rate for Participants With Symptomatic VTE/ VTE-Related Death With Onset During the Intended Treatment Period
ICAC adjudicated suspected symptomatic DVT and PE, and cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).
Time frame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Population: All randomized participants were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5mg BID | Event Rate for Participants With Symptomatic VTE/ VTE-Related Death With Onset During the Intended Treatment Period | 1.19 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate for Participants With Symptomatic VTE/ VTE-Related Death With Onset During the Intended Treatment Period | 0.81 percentage of participants |
95% CI: [0.72, 2.95]
95% CI: [-0.3, 1.06]
p-value: 0.2873test of equality
Secondary
Event Rate for Participants With VTE/Major Bleeding/All-Cause Death With Onset During the Intended Treatment Period
ICAC adjudicated VTE, acute clinically overt bleeding events, suspected thrombocytopenia, and cause of death. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed (%).
Time frame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Population: Randomized participants with an adjudicated and evaluable bilateral venogram or an adjudicated event associated with the endpoint, during the Intended Treatment Period, were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5mg BID | Event Rate for Participants With VTE/Major Bleeding/All-Cause Death With Onset During the Intended Treatment Period | 9.90 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate for Participants With VTE/Major Bleeding/All-Cause Death With Onset During the Intended Treatment Period | 10.60 percentage of participants |
95% CI: [0.74, 1.2]
95% CI: [-3.3, 1.63]
p-value: 0.6145test of equality
Secondary
Event Rate for Participants With VTE-Related Death With Onset During the Intended Treatment Period
ICAC adjudicated cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).
Time frame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Population: All randomized participants were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5mg BID | Event Rate for Participants With VTE-Related Death With Onset During the Intended Treatment Period | 0.13 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate for Participants With VTE-Related Death With Onset During the Intended Treatment Period | 0.00 percentage of participants |
95% CI: [-0.05, 0.3]
p-value: 0.1578test of equality
Secondary
Event Rate for Total Participants With Adjudicated VTE/All-Cause Death With Onset During the Intended Treatment Period
ICAC adjudicated all venograms, suspected symptomatic DVT and PE, and cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).
Time frame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Population: Randomized participants with either an adjudicated and evaluable bilateral proximal venogram or an adjudicated event associated with the endpoint, during the Intended Treatment Period, were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5mg BID | Event Rate for Total Participants With Adjudicated VTE/All-Cause Death With Onset During the Intended Treatment Period | 2.13 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate for Total Participants With Adjudicated VTE/All-Cause Death With Onset During the Intended Treatment Period | 1.97 percentage of participants |
95% CI: [0.63, 1.87]
95% CI: [-0.99, 1.21]
p-value: 0.77test of equality
Secondary
Event Rate for Total Participants With VTE/ VTE-Related Death With Onset During the Intended Treatment Period
ICAC adjudicated all venograms, suspected symptomatic DVT and PE, and cause of death. VTE includes DVT and PE. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).
Time frame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Population: Randomized participants with either an adjudicated and evaluable bilateral proximal venogram or an adjudicated event associated with the endpoint, during the Intended Treatment Period, were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5mg BID | Event Rate for Total Participants With VTE/ VTE-Related Death With Onset During the Intended Treatment Period | 2.05 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate for Total Participants With VTE/ VTE-Related Death With Onset During the Intended Treatment Period | 1.73 percentage of participants |
95% CI: [0.68, 2.11]
95% CI: [-0.78, 1.33]
p-value: 0.5443test of equality
Secondary
Event Rate of Adjudicated MI, Stroke, and Thrombocytopenia Events During the Follow-Up Period
A 60-day follow-up period started after the last dose of study drug and continued until the End of Study Visit on Day 72 (60 days ± 3 days, after the last dose of study drug). Event rate was number of participants with the endpoint divided by the number of participants analyzed (%). ICAC adjudicated acute clinically overt bleeding events, suspected thrombocytopenia, suspected acute MI, suspected acute stroke per ISTH guidelines modified for surgical patients.
Time frame: Post last dose of study drug to Day 72 (60 days)
Population: Participants who received at least one dose of study drug and entered the Follow-Up period
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban 2.5mg BID | Event Rate of Adjudicated MI, Stroke, and Thrombocytopenia Events During the Follow-Up Period | MI/Stroke | 0.06 percentage of participants |
| Apixaban 2.5mg BID | Event Rate of Adjudicated MI, Stroke, and Thrombocytopenia Events During the Follow-Up Period | MI | 0.06 percentage of participants |
| Apixaban 2.5mg BID | Event Rate of Adjudicated MI, Stroke, and Thrombocytopenia Events During the Follow-Up Period | Stroke | 0.00 percentage of participants |
| Apixaban 2.5mg BID | Event Rate of Adjudicated MI, Stroke, and Thrombocytopenia Events During the Follow-Up Period | Thrombocytopenia | 0.00 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate of Adjudicated MI, Stroke, and Thrombocytopenia Events During the Follow-Up Period | Thrombocytopenia | 0.00 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate of Adjudicated MI, Stroke, and Thrombocytopenia Events During the Follow-Up Period | MI/Stroke | 0.06 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate of Adjudicated MI, Stroke, and Thrombocytopenia Events During the Follow-Up Period | Stroke | 0.00 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate of Adjudicated MI, Stroke, and Thrombocytopenia Events During the Follow-Up Period | MI | 0.06 percentage of participants |
Secondary
Event Rate of Adjudicated VTE / VTE-related Death With Onset During the Treatment Period
VTE / VTE-related death was defined as the combination of fatal or non-fatal PE, and symptomatic or asymptomatic DVT. A mandatory bilateral ascending contrast venogram was performed on all participants after 12 days (±2 days) of study treatment. An ICAC adjudicated all venograms, suspected symptomatic DVT and PE, and cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).
Time frame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Population: Randomized participants with an adjudicated and evaluable bilateral venogram or an adjudicated event associated with the endpoint, during the Intended Treatment Period, were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5mg BID | Event Rate of Adjudicated VTE / VTE-related Death With Onset During the Treatment Period | 8.91 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Event Rate of Adjudicated VTE / VTE-related Death With Onset During the Treatment Period | 8.61 percentage of participants |
95% CI: [0.8, 1.35]
95% CI: [-2.04, 2.59]
p-value: 0.7754test of equality
Secondary
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
A mandatory bilateral ascending contrast venogram was performed on all participants after 12 days (±2 days) of study treatment. An ICAC adjudicated all venograms, suspected proximal DVT and non-fatal PE, and all-cause of death. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed and reported as percentage (%).
Time frame: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Population: Randomized participants with either an adjudicated and evaluable bilateral proximal venogram or an adjudicated non-fatal PE or death, during the Intended Treatment Period, were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5mg BID | 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 | 2.05 percentage of participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | 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 | 1.64 percentage of participants |
95% CI: [0.7, 2.23]
95% CI: [-0.68, 1.4]
p-value: 0.7779t-test, 1 sided
Secondary
Mean Change From Baseline in Heart Rate During the Treatment Period
Treatment Period=the period from first dose of study drug through 2 days after discontinuation of study drug (12 + 2 days). Baseline=measurement prior to first dose of study drug. Heart rate was measured during screening (pre-operative, post-operative) and in the treatment period on Days 1 (day of first dose), 2, 3, 4,12 (end of treatment). Heart rate was measured in beats per minute (bpm).
Time frame: Baseline to last dose of study drug, plus 2 days
Population: All participants who received at least one dose of study drug and had heart rate measurements at baseline were summarized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Apixaban 2.5mg BID | Mean Change From Baseline in Heart Rate During the Treatment Period | Heart Rate Day 2 (n=1575,1574) | 4.6 bpm | Standard Error 0.312 |
| Apixaban 2.5mg BID | Mean Change From Baseline in Heart Rate During the Treatment Period | Heart Rate Day 4 (n=127,134) | 7.6 bpm | Standard Error 1.365 |
| Apixaban 2.5mg BID | Mean Change From Baseline in Heart Rate During the Treatment Period | Heart Rate Day 3 (n=1490,1498) | 4.5 bpm | Standard Error 0.334 |
| Apixaban 2.5mg BID | Mean Change From Baseline in Heart Rate During the Treatment Period | Heart Rate Day 12 (n=1495, 1462) | -0.3 bpm | Standard Error 0.361 |
| Apixaban 2.5mg BID | Mean Change From Baseline in Heart Rate During the Treatment Period | Heart Rate Day 1 (n=240,237) | 2.3 bpm | Standard Error 0.761 |
| Enoxaparin 30 mg SC Injection q 12 Hours | Mean Change From Baseline in Heart Rate During the Treatment Period | Heart Rate Day 12 (n=1495, 1462) | -0.1 bpm | Standard Error 0.375 |
| Enoxaparin 30 mg SC Injection q 12 Hours | Mean Change From Baseline in Heart Rate During the Treatment Period | Heart Rate Day 1 (n=240,237) | 2.7 bpm | Standard Error 0.761 |
| Enoxaparin 30 mg SC Injection q 12 Hours | Mean Change From Baseline in Heart Rate During the Treatment Period | Heart Rate Day 2 (n=1575,1574) | 4.5 bpm | Standard Error 0.317 |
| Enoxaparin 30 mg SC Injection q 12 Hours | Mean Change From Baseline in Heart Rate During the Treatment Period | Heart Rate Day 3 (n=1490,1498) | 5.0 bpm | Standard Error 0.344 |
| Enoxaparin 30 mg SC Injection q 12 Hours | Mean Change From Baseline in Heart Rate During the Treatment Period | Heart Rate Day 4 (n=127,134) | 9.4 bpm | Standard Error 1.32 |
Secondary
Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period
Treatment Period=the period from first dose of study drug through 2 days after discontinuation of study drug (12 + 2 days). Baseline=measurement prior to first dose of study drug. Blood pressures (BP) were measured during screening (pre-operative, post-operative) and in the treatment period on Days 1 (day of first dose), 2, 3, 4,12 (end of treatment). Systolic and diastolic pressures were measured in millimeters of mercury (mmHg).
Time frame: Baseline to last dose of study drug, plus 2 days
Population: All participants who received at least one dose of study drug and had blood pressure measurements at baseline were summarized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Apixaban 2.5mg BID | Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period | Diastolic BP Day 1 (n=240, 237) | -0.4 mmHg | Standard Error 0.741 |
| Apixaban 2.5mg BID | Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period | Diastolic BP Day 2 (n=1577, 1574) | 1.7 mmHg | Standard Error 0.301 |
| Apixaban 2.5mg BID | Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period | Diastolic BP Day 3 (n=1489,1498) | 2.3 mmHg | Standard Error 0.322 |
| Apixaban 2.5mg BID | Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period | Diastolic BP Day 4 (n=127,134) | 0.6 mmHg | Standard Error 1.217 |
| Apixaban 2.5mg BID | Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period | Diastolic BP Day 12 (n=1495,1463) | 7.3 mmHg | Standard Error 0.342 |
| Apixaban 2.5mg BID | Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period | Systolic BP Day 1 (n=240,237) | 1.5 mmHg | Standard Error 1.189 |
| Apixaban 2.5mg BID | Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period | Systolic BP Day 2 (n=1577,1574) | 5.4 mmHg | Standard Error 0.505 |
| Apixaban 2.5mg BID | Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period | Systolic BP Day 3 (n=1489,1498) | 4.7 mmHg | Standard Error 0.536 |
| Apixaban 2.5mg BID | Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period | Systolic BP Day 4 (n=127,134) | 2.8 mmHg | Standard Error 2.129 |
| Apixaban 2.5mg BID | Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period | Systolic BP Day 12 (n=1495,1463) | 9.1 mmHg | Standard Error 0.543 |
| Enoxaparin 30 mg SC Injection q 12 Hours | Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period | Systolic BP Day 3 (n=1489,1498) | 4.3 mmHg | Standard Error 0.555 |
| Enoxaparin 30 mg SC Injection q 12 Hours | Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period | Diastolic BP Day 1 (n=240, 237) | -0.9 mmHg | Standard Error 0.738 |
| Enoxaparin 30 mg SC Injection q 12 Hours | Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period | Systolic BP Day 1 (n=240,237) | -0.7 mmHg | Standard Error 1.303 |
| Enoxaparin 30 mg SC Injection q 12 Hours | Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period | Diastolic BP Day 2 (n=1577, 1574) | 1.5 mmHg | Standard Error 0.305 |
| Enoxaparin 30 mg SC Injection q 12 Hours | Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period | Systolic BP Day 12 (n=1495,1463) | 8.9 mmHg | Standard Error 0.562 |
| Enoxaparin 30 mg SC Injection q 12 Hours | Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period | Diastolic BP Day 3 (n=1489,1498) | 2.1 mmHg | Standard Error 0.321 |
| Enoxaparin 30 mg SC Injection q 12 Hours | Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period | Systolic BP Day 2 (n=1577,1574) | 4.2 mmHg | Standard Error 0.518 |
| Enoxaparin 30 mg SC Injection q 12 Hours | Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period | Diastolic BP Day 4 (n=127,134) | 0.3 mmHg | Standard Error 1.104 |
| Enoxaparin 30 mg SC Injection q 12 Hours | Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period | Systolic BP Day 4 (n=127,134) | 1.4 mmHg | Standard Error 1.871 |
| Enoxaparin 30 mg SC Injection q 12 Hours | Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period | Diastolic BP Day 12 (n=1495,1463) | 7.5 mmHg | Standard Error 0.343 |
Secondary
Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period
Laboratory Chemistry profile was measured during screening (pre-operative, post-operative) and in the Treatment Period on Days 4, and 12 (end of treatment). Potassium: \< 0.9\*LLN or \> 1.1\*ULN, or if pre-dose \< LLN then use \< 0.9\*predose or \> ULN if pre-dose \> ULN then use \> 1.1\*predose or \< LLN. Calcium: \< 0.8\*LLN or \> 1.2\*ULN, or if pre-dose \< LLN then use \< 0.75\*predose or \> ULN If pre-dose \> ULN then use \> 1.25\*predose or \< LLN. Chloride: \< 0.9\*LLN or \> 1.1\*ULN, or if pre-dose \< LLN then use \< 0.9\*predose or \> ULN if pre-dose \> ULN then use \> 1.1\*predose or \< LLN. Sodium: \< 0.95\*LLN or \> 1.05\*ULN, or if pre-dose \< LLN then use \< 0.95\*predose or \>ULN if pre-dose \> ULN then use \> 1.05\*predose or \< LLN. Bicarbonate: \< 0.75\*LLN or \> 1.25\*ULN, or if pre-dose \< LLN then use \< 0.75\*predose or \> ULN if pre-dose \> ULN then use \> 1.25\*predose or \< LLN.
Time frame: First dose to last dose of study drug (12 days), plus 2 days
Population: All participants who received at least one dose of study drug and had available laboratory results for that analyte and treatment group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban 2.5mg BID | Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period | Calcium high (n=1569,1562) | 0 participants |
| Apixaban 2.5mg BID | Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period | Potassium low(n=1568,1559) | 54 participants |
| Apixaban 2.5mg BID | Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period | Chloride high (n=1568,1562) | 0 participants |
| Apixaban 2.5mg BID | Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period | Potassium high(n=1568,1559) | 26 participants |
| Apixaban 2.5mg BID | Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period | Chloride low (n=1568,1562) | 11 participants |
| Apixaban 2.5mg BID | Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period | Sodium low (n=1568,1562) | 23 participants |
| Apixaban 2.5mg BID | Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period | Bicarbonate low (n=1568,1561) | 11 participants |
| Apixaban 2.5mg BID | Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period | Sodium high (n=1568,1562) | 2 participants |
| Apixaban 2.5mg BID | Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period | Calcium low (n=1569,1562) | 1 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period | Sodium high (n=1568,1562) | 0 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period | Calcium low (n=1569,1562) | 5 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period | Calcium high (n=1569,1562) | 1 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period | Chloride low (n=1568,1562) | 17 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period | Chloride high (n=1568,1562) | 1 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period | Bicarbonate low (n=1568,1561) | 13 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period | Potassium low(n=1568,1559) | 56 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period | Potassium high(n=1568,1559) | 20 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period | Sodium low (n=1568,1562) | 39 participants |
Secondary
Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period
Treatment Period=the period from first dose of study drug through 2 days after discontinuation of study drug. Hematology profile was measured during screening (pre-operative, post-operative) and in the Treatment Period on Days 2, 3, 4, 12 (end of treatment). Upper limit of normal (ULN); lower limit of normal (LLN). Platelet Count low: \< 100,000/mm\^3 (or \< 100\*109 cells/L). Erythrocytes low: \< 0.75 \*pre-dose. Hemoglobin low: \> 2 g/dL decrease compared to pre-dose or Value ≤ 8 g/dL. Hematocrit low: \< 0.75\*pre-dose . Leukocytes: \< 0.75\*LLN or \> 1.25\* ULN, or if pre-dose \< LLN then use \< 0.8\*predose or \> ULN if pre-dose \> ULN then use \> 1.2\*predose or \< LLN. Lymphocytes (absolute): \< 0.750\*10\^3 cells/µL or \> 7.50\*10\^3 cells/ µL. Eosinophils (absolute) high: \> 0.750\*10\^3 cells/µL. Basophils(absolute) high: \> 400/mm\^3 (or \> 0.4\*103 cells/µL). Monocytes (absolute) high: \> 2000/mm\^3 (or \> 2\*103 cells/µL). Neutrophils(absolute) high: \< 1.0\*103 cells/µL.
Time frame: First dose to last dose of study drug (12 days), plus 2 days
Population: All participants who received at least one dose of study drug and had available laboratory results for that analyte and treatment group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban 2.5mg BID | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Hemoglobin low (n=1561,1549) | 386 participants |
| Apixaban 2.5mg BID | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Hematocrit low (n=1558,1547) | 135 participants |
| Apixaban 2.5mg BID | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Platelet count low (n=1556,1543) | 6 participants |
| Apixaban 2.5mg BID | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Erythrocytes low (n=1557,1547) | 130 participants |
| Apixaban 2.5mg BID | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Leukocytes low(n=1583,1572) | 8 participants |
| Apixaban 2.5mg BID | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Leukocytes high(n=1583,1572) | 214 participants |
| Apixaban 2.5mg BID | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Basophils high (n=1577, 1564) | 0 participants |
| Apixaban 2.5mg BID | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Eosinophils high (n=1577, 1564) | 32 participants |
| Apixaban 2.5mg BID | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Lymphocytes low (n=1577,1564) | 125 participants |
| Apixaban 2.5mg BID | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Lymphocytes high (n=1577,1564) | 2 participants |
| Apixaban 2.5mg BID | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Monocytes high (n=1577,1564) | 4 participants |
| Apixaban 2.5mg BID | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Neutrophils low (n=1577,1564) | 4 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Monocytes high (n=1577,1564) | 4 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Hemoglobin low (n=1561,1549) | 392 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Basophils high (n=1577, 1564) | 2 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Hematocrit low (n=1558,1547) | 157 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Lymphocytes high (n=1577,1564) | 4 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Platelet count low (n=1556,1543) | 9 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Eosinophils high (n=1577, 1564) | 13 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Erythrocytes low (n=1557,1547) | 149 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Neutrophils low (n=1577,1564) | 5 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Leukocytes low(n=1583,1572) | 11 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Lymphocytes low (n=1577,1564) | 117 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period | Leukocytes high(n=1583,1572) | 210 participants |
Secondary
Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period
Treatment Period=the period from first dose of study drug through 2 days after discontinuation of study drug. Laboratory Chemistry profile was measured during screening (pre-operative, post-operative) and in the Treatment Period on Days 4, and 12 (end of treatment). Bilirubin (direct) high: \> 1.5\*ULN. Total bilirubin: : \> 2\*ULN, Alanine Aminotransferase (ALT) high: \> 3\*ULN. Alkaline Phosphatase (ALP): \> 2\*ULN. Aspartate Aminotransferase (AST): \> 3\*ULN. Creatinine: \> 1.5\*ULN.
Time frame: First dose to last dose of study drug (12 days), plus 2 days
Population: All participants who received at least one dose of study drug and had available laboratory results for that analyte and treatment group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban 2.5mg BID | Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period | ALP high (n=1573,1563) | 42 participants |
| Apixaban 2.5mg BID | Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period | ALT high (n=1573,1562) | 33 participants |
| Apixaban 2.5mg BID | Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period | AST high (n=1573,1562) | 29 participants |
| Apixaban 2.5mg BID | Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period | Bilirubin direct high (n=1563,1553) | 63 participants |
| Apixaban 2.5mg BID | Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period | Bilirubin total high(n=1572,1562) | 2 participants |
| Apixaban 2.5mg BID | Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period | Creatinine high (n=1569,1562) | 17 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period | Bilirubin total high(n=1572,1562) | 8 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period | ALP high (n=1573,1563) | 55 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period | Bilirubin direct high (n=1563,1553) | 54 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period | ALT high (n=1573,1562) | 45 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period | Creatinine high (n=1569,1562) | 28 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period | AST high (n=1573,1562) | 40 participants |
Secondary
Number of Participants With Other Chemistry Laboratory Marked Abnormalities During the Treatment Period
Treatment Period=the period from first dose of study drug through 2 days after discontinuation of study drug. Laboratory Chemistry profile was measured during screening (pre-operative, post-operative) and in the Treatment Period on Days 4, and 12 (end of treatment). Fasting Glucose: if pre-dose \< LLN then use \< 0.8\*predose; or \> ULN if pre-dose \> ULN then use \> 2.0\*predose or \<LLN. Total Protein: \< 0.9\*LLN or \> 1.1\*ULN, or if pre-dose \< LLN then use 0.9\*predose or \> ULN if pre-dose \> ULN then use 1.1\*predose or \< LLN. Uric Acid: \> 1.5\*ULN, or if pre-dose \> ULN then use \> 2\*predose. Creatine Kinase (CK): \> 5\*ULN.
Time frame: First dose to last dose of study drug (12 days), plus 2 days
Population: All participants who received at least one dose of study drug and had available laboratory results for that analyte and treatment group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban 2.5mg BID | Number of Participants With Other Chemistry Laboratory Marked Abnormalities During the Treatment Period | CK high (n=1573,1563) | 52 participants |
| Apixaban 2.5mg BID | Number of Participants With Other Chemistry Laboratory Marked Abnormalities During the Treatment Period | Fasting Glucose low (n=611, 579) | 8 participants |
| Apixaban 2.5mg BID | Number of Participants With Other Chemistry Laboratory Marked Abnormalities During the Treatment Period | Fasting Glucose high (n=611, 579) | 54 participants |
| Apixaban 2.5mg BID | Number of Participants With Other Chemistry Laboratory Marked Abnormalities During the Treatment Period | Total Protein low (n=1568,1562) | 527 participants |
| Apixaban 2.5mg BID | Number of Participants With Other Chemistry Laboratory Marked Abnormalities During the Treatment Period | Uric Acid high (n=1567,1562) | 22 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Other Chemistry Laboratory Marked Abnormalities During the Treatment Period | Uric Acid high (n=1567,1562) | 12 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Other Chemistry Laboratory Marked Abnormalities During the Treatment Period | Total Protein low (n=1568,1562) | 513 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Other Chemistry Laboratory Marked Abnormalities During the Treatment Period | Fasting Glucose low (n=611, 579) | 5 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Other Chemistry Laboratory Marked Abnormalities During the Treatment Period | CK high (n=1573,1563) | 45 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Other Chemistry Laboratory Marked Abnormalities During the Treatment Period | Fasting Glucose high (n=611, 579) | 28 participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), AEs Leading to Discontinuation, and Deaths - Treated Population
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 last dose, plus 2 days for AEs (12 + 2 days) or plus 30 days for SAEs (12 + 30 days)
Population: All participants who received at least 1 dose of study drug during the Treatment Period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban 2.5mg BID | Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), AEs Leading to Discontinuation, and Deaths - Treated Population | SAE | 123 participants |
| Apixaban 2.5mg BID | Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), AEs Leading to Discontinuation, and Deaths - Treated Population | AEs leading to discontinuation | 60 participants |
| Apixaban 2.5mg BID | Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), AEs Leading to Discontinuation, and Deaths - Treated Population | Bleeding AE | 110 participants |
| Apixaban 2.5mg BID | Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), AEs Leading to Discontinuation, and Deaths - Treated Population | Deaths | 3 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), AEs Leading to Discontinuation, and Deaths - Treated Population | Bleeding AE | 144 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), AEs Leading to Discontinuation, and Deaths - Treated Population | SAE | 123 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), AEs Leading to Discontinuation, and Deaths - Treated Population | Deaths | 5 participants |
| Enoxaparin 30 mg SC Injection q 12 Hours | Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), AEs Leading to Discontinuation, and Deaths - Treated Population | AEs leading to discontinuation | 58 participants |