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 whether apixaban prevents the development of blood clots in the leg (deep vein thrombosis) and lung (pulmonary embolism), which sometimes occur after knee replacement surgery, and to compare the efficacy of apixaban with that of enoxaparin (Lovenox®) in the prevention of these clots. The safety of apixaban will also be studied.
Interventions
DRUGEnoxaparin
40 mg, administered once daily by subcutaneous injection, for 12 days
DRUGApixaban
2.5 mg, administered twice daily as tablets, for 12 days
Administered once daily by subcutaneous injection
Oral tablet administered twice daily
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria * Patients scheduled for either elective unilateral or same-day bilateral total knee replacement surgery (TKR) or a revision of at least 1 component of a TKR * Patients willing and able to undergo bilateral ascending contrast venography Key
Exclusion criteria
* Known or suspected hereditary or acquired bleeding or coagulation disorders in the participant or his or her first-degree relative * Known or suspected history of heparin-induced thrombocytopenia * Known coagulopathy * Active bleeding or at high risk for bleeding * Brain, spinal, ophthalmologic, or major surgery or trauma within the past 90 days * Active hepatobiliary disease * Alcohol and/or substance abuse within the past year * Any condition for which, in the opinion of the investigator, surgery or administration of an anticoagulant was contraindicated * Two consecutive blood pressure readings within 15 to 30 minutes with supine systolic blood pressure \>180 mm Hg or supine diastolic blood pressure \>105 mm Hg * Clinically significant laboratory abnormalities at the enrollment visit: * Hemoglobin \<10 g/dL * Platelet count \<100,000/mm\^3 * Creatinine clearance \<30 mL/min, as estimated by the method of Cockcroft and Gault * Alanine aminotransferase or aspartate aminotransferase level \>2\*upper limit of normal (ULN) or a total bilirubin ≥1.5\*ULN (unless an alternative causative factor such as Gilbert's syndrome was identified)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Adjudicated Venous Thromboembolic Event-related and All-cause Deaths With Onset During the Intended-treatment Period | Day of randomization to later of 2 days after last dose or 14 days after first dose; 14 days after randomization for those who did not receive study drug | Event rate=Number of events divided by the number of patients evaluated. Intended treatment period starts on the day of randomization, and for those who received study drug, ends at the later of 2 days after last dose or 14 days after the first dose of study drug; for randomized patients who did not receive study drug, the period ends 14 days after randomization.Venous thromboembolic event (VTE)=nonfatal pulmonary embolism (PE), symptomatic deep vein thrombosis (DVT), or asymptomatic proximal DVT detected by ultrasound. VTE-related death=fatal PE or sudden death for which VTE could not be excluded as a cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Adjudicated Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism, and Venous Thromboembolic Event-related Death With Onset During the Intended Treatment Period | Day of randomization to later of 2 days after last dose or 14 days after first dose; 14 days after randomization for those who did not receive study | Event rate=Number of events divided by the number of patients evaluated. Intended treatment period starts on the day of randomization, and for those who received study drug, ends at the later of 2 days after last dose or 14 days after the first dose of study drug; for randomized patients who did not receive study drug, the period ends 14 days after randomization; for randomized patients who did not receive study drug, the period ends 14 days after randomization. Venous thromboembolic event (VTE)=nonfatal pulmonary embolism (PE), symptomatic DVT, or asymptomatic proximal DVT detected by ultrasound. VTE-related death=fatal PE or sudden death for which VTE could not be excluded as a cause. |
| Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), and Major Bleeding or CRNM | Days 1 to 12 | Event rate=Number of events divided by number of patients evaluated. Adjusted difference of event rates takes into consideration type of surgery as a stratification factor. Bleeding Criteria: Major bleeding=an event consisting of clinically overt bleeding accompanied by a decrease in hemoglobin of 2 g/dL or more and/or a transfusion of 2 or more units of packed red blood cells; bleeding that occurred in at least 1 of the following critical sites: intracranial, intraspinal, intraocular (within the corpus of the eye; a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, and retroperitoneal; bleeding that was fatal. CRNM bleeding= clinically overt bleeding; that satisfies none of the additional criteria required for the event to be adjudicated as a major bleeding event; that led to either hospital admission for bleeding, physician-guided medical or surgical treatment for bleeding; or a change in antithrombic treatment. |
| Number of Participants With Serious Adverse Events (SAE), Bleeding Adverse Events (AEs), Discontinuations Due to AEs, and Death as Outcome | Days 1 through 12 + 2 days (nonserious AEs, bleeding AES) or 30 days (SAES, deaths) after 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. Bleeding AEs=all serious or nonserious bleeding-related AEs. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Randomization to Days 2, 3, 4, and 12 (±2 days) and at Days 42 and 72 (±5 days) of follow-up | preRX=pretreatment; LLN=lower limit of normal; ULN=upper limit of normal. Calcium, total (mg/dL): \<0.8\*LLN or \>1.2\*ULN, or if preRx\<LLN use \<0.75\*preRx or \>ULN if preRx \>ULN use \>1.25\*preRx or \<LLN; chloride, serum (mEq/L): \<0.9\*LLN or \>1.1\*ULN, or if preRx\<LLN use \<0.9\*preRx or \>ULN if preRx\>ULN use \>1.1\*preRx or \<LLN; bicarbonate (mEq/L): \<0.75\*LLN or \>1.25\*ULN, or if preRx \< LLN use \<0.75\*preRx or \>ULN if preRx \>ULN use \>1.25\*preRx or \< LLN; potassium, serum (mEq/L): \<0.9\* LLN or \>1.1\*ULN, or if preRx\<LLN use \<0.9 \*preRx or \>ULN if preRx\>ULN use \>1.1\*preRx or \<LLN; sodium, serum (mEq/L): \<0.95\*LLN or \>1.05\*ULN, or if preRx \<LLN use \<0.95\*preRx or \>ULN if preRx\>ULN use \>1.05\*preRx or \<LLN; protein, total (g/dL): \<0.9\*LLN or \>1.1\*ULN, or if preRx \<LLN use 0.9\*preRx or \>ULN if preRx \>ULN use 1.1\*preRx or \<LLN; CK (U/L): \>5\*ULN; uric acid (mg/dL): \>1.5\*ULN, or if preRx \>ULN use \>2\*preRx; glucose, fasting serum (mg/dL): \<0.8\*LLN or \>1.5\*ULN, or if preRx \<LLN use \<0.8\*preRx or \>ULN. |
| Summary of Laboratory Marked Abnormalities in Urinalysis Results During the Treatment Period-Treated Subjects With Available Measurements (Urinalysis) | Randomization to Days 2, 3, 4, and 12 (±2 days) and at Days 42 and 72 (± 5 days) of follow-up | preRX=pretreatment. Blood, urine: If missing preRx use ≥2, or if value ≥4, or if preRx=0 or 0.5 use ≥2, or if preRx=1 use ≥3, or if preRx=2 or 3 use ≥4; glucose, urine: If missing preRx use ≥2, or if value ≥4, or if preRx=0 or 0.5 use ≥2, or if preRx=1 use ≥3, or if preRx=2 or 3 use ≥4; protein, urine: If missing preRx use ≥ 2, or if value ≥4, or if preRx=0 or 0.5 use ≥2, or if preRx=1 use ≥3, or if preRx=2 or 3 use ≥4; Red blood cells , urine: If missing preRx use ≥2, or if value ≥4, or if preRx=0 or 0.5 use ≥2, or if preRx=1 use ≥3, or if preRx=2 or 3 use ≥4; white blood cells, urine: If missing preRx use ≥2, or if value ≥4, or if preRx=0 or 0.5 use ≥2, or if preRx=1 use ≥3, or if preRx=2 or 3 use ≥4. |
| Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Randomization to Days 2, 3, 4, and 12 (±2 days) and at Days 42 and 72 (±5 days) of follow-up | preRX=pretreatment; LLN=lower limit of normal; ULN=upper limit of normal; abs=absolute. Hemoglobin (g/dL): \>2 decrease from preRx value or value \<=8; hematocrit (%): \<0.75\*preRx; platelets: \<100\*10\^9 cells/L; erythrocytes (\*10\^6 cells/μL): \<0.75\*preRx; leukocytes: \<0.75\*LLN or \>1.25\*ULN, or if preRx \<LLN, use \<0.8\*preRx or \>ULN if preRx \>ULN use \>1.2\*preRx or \<LLN; abs basophils: \>400/mm\^3; abs eosinophils: \> 0.750\*10\^3 cells/µL; abs lymphocytes: \<0.750\*10\*3 cells/ µL or \>7.50\*10\^3 c/ µL; abs monocytes \> 2000/mm\^3; abs neutrophils: \<1.0\*10\^3 cells/μL; ALP (U/L): \>2\*ULN; ALT, AST (U/L): \>3\*ULN; U/L; bilirubin, direct (mg/dL): \>1.5\*ULN; bilirubin, total (mg/dL): \>2\*ULN; BUN (mg/dL): \>2\*ULN; creatinine (mg/dL): \>1.5\*ULN. |
Countries
Austria, Belgium, Brazil, Chile, China, Colombia, Czechia, Denmark, France, Germany, Hungary, India, Israel, Italy, Malaysia, Mexico, Norway, Philippines, Poland, Russia, Singapore, South Africa, South Korea, Spain, Sweden, Ukraine, United Kingdom
Participant flow
Pre-assignment details
Of 3221 patients enrolled, 3057 were randomized. Primary participants=those who were randomized and had an adjudicated evaluable bilateral venogram or an adjudicated venous thromboembolic event or died. Evaluable participants=those with significant protocol deviations expected to affect the primary endpoint.
Participants by arm
| Arm | Count |
|---|---|
| Apixaban, 2.5 mg BID + Placebo Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD) | 1,528 |
| Enoxaparin, 40 mg QD + Placebo Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID | 1,529 |
| Total | 3,057 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 40 | 44 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | No longer met study criteria | 18 | 22 |
| Overall Study | Other | 7 | 11 |
| Overall Study | Poor compliance/noncompliance | 1 | 2 |
| Overall Study | Withdrawal by Subject | 68 | 57 |
Baseline characteristics
| Characteristic | Apixaban, 2.5 mg BID + Placebo | Enoxaparin, 40 mg QD + Placebo | Total |
|---|---|---|---|
| Age, Continuous | 67 Years STANDARD_DEVIATION 9.85 | 67 Years STANDARD_DEVIATION 9.82 | 67 Years STANDARD_DEVIATION 9.84 |
| Age, Customized 65 years to younger than 75 years | 608 Participants | 576 Participants | 1184 Participants |
| Age, Customized 75 years and older | 288 Participants | 317 Participants | 605 Participants |
| Age, Customized Younger than 65 years | 632 Participants | 636 Participants | 1268 Participants |
| Race/Ethnicity, Customized Asian | 252 Participants | 254 Participants | 506 Participants |
| Race/Ethnicity, Customized Black/African American | 14 Participants | 17 Participants | 31 Participants |
| Race/Ethnicity, Customized Ethnicity not reported | 1475 Participants | 1471 Participants | 2946 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian/Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Not Hispanic/Latino | 53 Participants | 57 Participants | 110 Participants |
| Race/Ethnicity, Customized Other [Not specified] | 45 Participants | 46 Participants | 91 Participants |
| Race/Ethnicity, Customized White | 1216 Participants | 1211 Participants | 2427 Participants |
| Region of Enrollment Austria | 156 Participants | 151 Participants | 307 Participants |
| Region of Enrollment Belgium | 27 Participants | 25 Participants | 52 Participants |
| Region of Enrollment Brazil | 17 Participants | 17 Participants | 34 Participants |
| Region of Enrollment Chile | 1 Participants | 5 Participants | 6 Participants |
| Region of Enrollment China | 90 Participants | 90 Participants | 180 Participants |
| Region of Enrollment Colombia | 36 Participants | 35 Participants | 71 Participants |
| Region of Enrollment Czech Republic | 48 Participants | 50 Participants | 98 Participants |
| Region of Enrollment Denmark | 26 Participants | 23 Participants | 49 Participants |
| Region of Enrollment France | 72 Participants | 68 Participants | 140 Participants |
| Region of Enrollment Germany | 122 Participants | 122 Participants | 244 Participants |
| Region of Enrollment Hungary | 17 Participants | 19 Participants | 36 Participants |
| Region of Enrollment India | 92 Participants | 92 Participants | 184 Participants |
| Region of Enrollment Israel | 43 Participants | 43 Participants | 86 Participants |
| Region of Enrollment Italy | 69 Participants | 69 Participants | 138 Participants |
| Region of Enrollment Korea, Republic of | 40 Participants | 38 Participants | 78 Participants |
| Region of Enrollment Malaysia | 4 Participants | 4 Participants | 8 Participants |
| Region of Enrollment Mexico | 60 Participants | 59 Participants | 119 Participants |
| Region of Enrollment Norway | 35 Participants | 36 Participants | 71 Participants |
| Region of Enrollment Philippines | 12 Participants | 14 Participants | 26 Participants |
| Region of Enrollment Poland | 41 Participants | 45 Participants | 86 Participants |
| Region of Enrollment Russian Federation | 150 Participants | 156 Participants | 306 Participants |
| Region of Enrollment Singapore | 8 Participants | 9 Participants | 17 Participants |
| Region of Enrollment South Africa | 56 Participants | 56 Participants | 112 Participants |
| Region of Enrollment Spain | 61 Participants | 60 Participants | 121 Participants |
| Region of Enrollment Sweden | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Ukraine | 181 Participants | 182 Participants | 363 Participants |
| Region of Enrollment United Kingdom | 63 Participants | 61 Participants | 124 Participants |
| Sex: Female, Male Female | 1089 Participants | 1127 Participants | 2216 Participants |
| Sex: Female, Male Male | 439 Participants | 402 Participants | 841 Participants |
| Type of Risk Factor Deep vein thrombosis | 36 Participants | 32 Participants | 68 Participants |
| Type of Risk Factor Hip or knee fracture surgery | 55 Participants | 49 Participants | 104 Participants |
| Type of Risk Factor Hip replacement | 90 Participants | 80 Participants | 170 Participants |
| Type of Risk Factor Knee replacement | 257 Participants | 286 Participants | 543 Participants |
| Type of Risk Factor Pulmonary embolism | 10 Participants | 10 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 295 / 1,501 | 342 / 1,508 |
| serious Total, serious adverse events | 72 / 1,501 | 88 / 1,508 |
Outcome results
Primary
Rate of Adjudicated Venous Thromboembolic Event-related and All-cause Deaths With Onset During the Intended-treatment Period
Event rate=Number of events divided by the number of patients evaluated. Intended treatment period starts on the day of randomization, and for those who received study drug, ends at the later of 2 days after last dose or 14 days after the first dose of study drug; for randomized patients who did not receive study drug, the period ends 14 days after randomization.Venous thromboembolic event (VTE)=nonfatal pulmonary embolism (PE), symptomatic deep vein thrombosis (DVT), or asymptomatic proximal DVT detected by ultrasound. VTE-related death=fatal PE or sudden death for which VTE could not be excluded as a cause.
Time frame: Day of randomization to later of 2 days after last dose or 14 days after first dose; 14 days after randomization for those who did not receive study drug
Population: The primary efficacy data set (all randomized participants who, during the Intended Treatment Period, had an adjudicated and evaluable bilateral venogram, an adjudicated venous thrombolytic event; or died due to any cause.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban, 2.5 mg BID + Placebo | Rate of Adjudicated Venous Thromboembolic Event-related and All-cause Deaths With Onset During the Intended-treatment Period | 15.06 Percentage of events/patients evaluated |
| Enoxaparin, 40 mg QD + Placebo | Rate of Adjudicated Venous Thromboembolic Event-related and All-cause Deaths With Onset During the Intended-treatment Period | 24.37 Percentage of events/patients evaluated |
Comparison: Sequential testing was used to control for overall type-I error and to compare the effect of apixaban with that of enoxaparin. Noninferiority (NI) of apixaban compared with enoxaparin for primary endpoint was tested first at 1-sided α=0.025 level. If NI on primary endpoint was demonstrated, superiority for the endpoint was then tested at 1-sided α=0.025 level. If superiority was demonstrated on the primary endpoint, NI was then tested on the key secondary endpoint at 1-sided α=0.025 level.p-value: <0.000195% CI: [0.51, 0.74]Yanagawa, Tango, and Hiejima test
Comparison: Sequential testing was used to control for overall type-I error and to compare the effect of apixaban with that of enoxaparin. Noninferiority (NI) of apixaban compared with enoxaparin for primary endpoint was tested first at 1-sided α=0.025 level. If NI on primary endpoint was demonstrated, superiority for the endpoint was then tested at 1-sided α=0.025 level. If superiority was demonstrated on the primary endpoint, NI was then tested on the key secondary endpoint at 1-sided α=0.025 level.p-value: <0.000195% CI: [-12.74, -5.79]Yanagawa, Tango, and Hiejima test
Secondary
Number of Participants With Serious Adverse Events (SAE), Bleeding Adverse Events (AEs), Discontinuations Due to AEs, and Death as Outcome
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. Bleeding AEs=all serious or nonserious bleeding-related AEs.
Time frame: Days 1 through 12 + 2 days (nonserious AEs, bleeding AES) or 30 days (SAES, deaths) after last dose of study drug
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban, 2.5 mg BID + Placebo | Number of Participants With Serious Adverse Events (SAE), Bleeding Adverse Events (AEs), Discontinuations Due to AEs, and Death as Outcome | SAE | 72 Participants |
| Apixaban, 2.5 mg BID + Placebo | Number of Participants With Serious Adverse Events (SAE), Bleeding Adverse Events (AEs), Discontinuations Due to AEs, and Death as Outcome | Bleeding AE | 90 Participants |
| Apixaban, 2.5 mg BID + Placebo | Number of Participants With Serious Adverse Events (SAE), Bleeding Adverse Events (AEs), Discontinuations Due to AEs, and Death as Outcome | Discontinuations due to AEs | 40 Participants |
| Apixaban, 2.5 mg BID + Placebo | Number of Participants With Serious Adverse Events (SAE), Bleeding Adverse Events (AEs), Discontinuations Due to AEs, and Death as Outcome | Deaths | 2 Participants |
| Enoxaparin, 40 mg QD + Placebo | Number of Participants With Serious Adverse Events (SAE), Bleeding Adverse Events (AEs), Discontinuations Due to AEs, and Death as Outcome | Deaths | 0 Participants |
| Enoxaparin, 40 mg QD + Placebo | Number of Participants With Serious Adverse Events (SAE), Bleeding Adverse Events (AEs), Discontinuations Due to AEs, and Death as Outcome | SAE | 88 Participants |
| Enoxaparin, 40 mg QD + Placebo | Number of Participants With Serious Adverse Events (SAE), Bleeding Adverse Events (AEs), Discontinuations Due to AEs, and Death as Outcome | Discontinuations due to AEs | 44 Participants |
| Enoxaparin, 40 mg QD + Placebo | Number of Participants With Serious Adverse Events (SAE), Bleeding Adverse Events (AEs), Discontinuations Due to AEs, and Death as Outcome | Bleeding AE | 112 Participants |
Secondary
Rate of Adjudicated Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism, and Venous Thromboembolic Event-related Death With Onset During the Intended Treatment Period
Event rate=Number of events divided by the number of patients evaluated. Intended treatment period starts on the day of randomization, and for those who received study drug, ends at the later of 2 days after last dose or 14 days after the first dose of study drug; for randomized patients who did not receive study drug, the period ends 14 days after randomization; for randomized patients who did not receive study drug, the period ends 14 days after randomization. Venous thromboembolic event (VTE)=nonfatal pulmonary embolism (PE), symptomatic DVT, or asymptomatic proximal DVT detected by ultrasound. VTE-related death=fatal PE or sudden death for which VTE could not be excluded as a cause.
Time frame: Day of randomization to later of 2 days after last dose or 14 days after first dose; 14 days after randomization for those who did not receive study
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban, 2.5 mg BID + Placebo | Rate of Adjudicated Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism, and Venous Thromboembolic Event-related Death With Onset During the Intended Treatment Period | 1.09 Percentage of events/patients evaluated |
| Enoxaparin, 40 mg QD + Placebo | Rate of Adjudicated Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism, and Venous Thromboembolic Event-related Death With Onset During the Intended Treatment Period | 2.17 Percentage of events/patients evaluated |
Comparison: Sequential testing was used to control for overall type-I error and to compare the effect of apixaban with that of enoxaparin. Noninferiority (NI) of apixaban compared with enoxaparin for primary endpoint was tested first at 1-sided α=0.025 level. If superiority was demonstrated on the primary endpoint, NI was then tested on the secondary endpoint at a 1-sided α=0.025 level. If NI of the secondary endpoint was demonstrated, superiority was then tested at the 1-sided α=0.025 level.p-value: 0.0003Yanagawa, Tango, and Hiejima test
Comparison: Sequential testing was used to control for overall type-I error and to compare the effect of apixaban with that of enoxaparin. Noninferiority (NI) of apixaban compared with enoxaparin for primary endpoint was tested first at 1-sided α=0.025 level. If superiority was demonstrated on the primary endpoint, NI was then tested on the secondary endpoint at a 1-sided α=0.025 level. If NI of the secondary endpoint was demonstrated, superiority was then tested at the 1-sided α=0.025 level.95% CI: [-2.03, -0.05]Inverse variance method
Secondary
Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), and Major Bleeding or CRNM
Event rate=Number of events divided by number of patients evaluated. Adjusted difference of event rates takes into consideration type of surgery as a stratification factor. Bleeding Criteria: Major bleeding=an event consisting of clinically overt bleeding accompanied by a decrease in hemoglobin of 2 g/dL or more and/or a transfusion of 2 or more units of packed red blood cells; bleeding that occurred in at least 1 of the following critical sites: intracranial, intraspinal, intraocular (within the corpus of the eye; a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, and retroperitoneal; bleeding that was fatal. CRNM bleeding= clinically overt bleeding; that satisfies none of the additional criteria required for the event to be adjudicated as a major bleeding event; that led to either hospital admission for bleeding, physician-guided medical or surgical treatment for bleeding; or a change in antithrombic treatment.
Time frame: Days 1 to 12
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban, 2.5 mg BID + Placebo | Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), and Major Bleeding or CRNM | Major bleeding (n=9, 14) | 0.60 Percentage of events/patients evaluated |
| Apixaban, 2.5 mg BID + Placebo | Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), and Major Bleeding or CRNM | CRNM (n=44, 58) | 2.93 Percentage of events/patients evaluated |
| Apixaban, 2.5 mg BID + Placebo | Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), and Major Bleeding or CRNM | Major bleeding or CRNM (n=53, 72) | 3.53 Percentage of events/patients evaluated |
| Apixaban, 2.5 mg BID + Placebo | Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), and Major Bleeding or CRNM | Any bleeding | 6.93 Percentage of events/patients evaluated |
| Enoxaparin, 40 mg QD + Placebo | Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), and Major Bleeding or CRNM | Any bleeding | 8.36 Percentage of events/patients evaluated |
| Enoxaparin, 40 mg QD + Placebo | Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), and Major Bleeding or CRNM | Major bleeding (n=9, 14) | 0.93 Percentage of events/patients evaluated |
| Enoxaparin, 40 mg QD + Placebo | Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), and Major Bleeding or CRNM | Major bleeding or CRNM (n=53, 72) | 4.77 Percentage of events/patients evaluated |
| Enoxaparin, 40 mg QD + Placebo | Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), and Major Bleeding or CRNM | CRNM (n=44, 58) | 3.85 Percentage of events/patients evaluated |
Comparison: Major bleedingp-value: 0.301495% CI: [-0.95, 0.29]Mantel Haenszel
Comparison: CRNMp-value: 0.166895% CI: [-2.2, 0.38]Mantel Haenszel
Comparison: Major or CRNMp-value: 0.088195% CI: [-2.66, 0.18]Mantel Haenszel
Comparison: Any bleedingp-value: 0.141295% CI: [-3.29, 0.51]Mantel Haenszel
Other Pre-specified
Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements)
preRX=pretreatment; LLN=lower limit of normal; ULN=upper limit of normal. Calcium, total (mg/dL): \<0.8\*LLN or \>1.2\*ULN, or if preRx\<LLN use \<0.75\*preRx or \>ULN if preRx \>ULN use \>1.25\*preRx or \<LLN; chloride, serum (mEq/L): \<0.9\*LLN or \>1.1\*ULN, or if preRx\<LLN use \<0.9\*preRx or \>ULN if preRx\>ULN use \>1.1\*preRx or \<LLN; bicarbonate (mEq/L): \<0.75\*LLN or \>1.25\*ULN, or if preRx \< LLN use \<0.75\*preRx or \>ULN if preRx \>ULN use \>1.25\*preRx or \< LLN; potassium, serum (mEq/L): \<0.9\* LLN or \>1.1\*ULN, or if preRx\<LLN use \<0.9 \*preRx or \>ULN if preRx\>ULN use \>1.1\*preRx or \<LLN; sodium, serum (mEq/L): \<0.95\*LLN or \>1.05\*ULN, or if preRx \<LLN use \<0.95\*preRx or \>ULN if preRx\>ULN use \>1.05\*preRx or \<LLN; protein, total (g/dL): \<0.9\*LLN or \>1.1\*ULN, or if preRx \<LLN use 0.9\*preRx or \>ULN if preRx \>ULN use 1.1\*preRx or \<LLN; CK (U/L): \>5\*ULN; uric acid (mg/dL): \>1.5\*ULN, or if preRx \>ULN use \>2\*preRx; glucose, fasting serum (mg/dL): \<0.8\*LLN or \>1.5\*ULN, or if preRx \<LLN use \<0.8\*preRx or \>ULN.
Time frame: Randomization to Days 2, 3, 4, and 12 (±2 days) and at Days 42 and 72 (±5 days) of follow-up
Population: All participants who received at least 1 dose of study drug. n=number of participants with available measurements
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Calcium, total (low) (n=1447, 1457) | 5 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Chloride, serum (low)(n=1442, 1454) | 1 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Bicarbonate (low) (n=1435, 1447) | 0 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Potassium, serum (low) (n=1438, 1453) | 38 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Potassium, serum (high)(n=1438, 1453) | 34 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Sodium, serum (low) (n=1442, 1454) | 5 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Sodium, serum (high) (n=1442, 1454) | 1 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Glucose, fasting serum (low) (n=715, 713) | 8 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Glucose, fasting serum (high) (n=715, 713) | 46 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Protein, total (low) (n=1447, 1457 | 223 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Creatine kinase (CK) (high) (n=1463, 1476) | 66 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Uric acid (high) (n=1446, 1458) | 1 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Creatine kinase (CK) (high) (n=1463, 1476) | 65 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Calcium, total (low) (n=1447, 1457) | 9 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Sodium, serum (high) (n=1442, 1454) | 0 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Chloride, serum (low)(n=1442, 1454) | 0 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Protein, total (low) (n=1447, 1457 | 243 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Bicarbonate (low) (n=1435, 1447) | 3 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Glucose, fasting serum (low) (n=715, 713) | 1 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Potassium, serum (low) (n=1438, 1453) | 41 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Uric acid (high) (n=1446, 1458) | 2 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Potassium, serum (high)(n=1438, 1453) | 40 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Glucose, fasting serum (high) (n=715, 713) | 25 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements) | Sodium, serum (low) (n=1442, 1454) | 10 Participants |
Other Pre-specified
Summary of Laboratory Marked Abnormalities in Urinalysis Results During the Treatment Period-Treated Subjects With Available Measurements (Urinalysis)
preRX=pretreatment. Blood, urine: If missing preRx use ≥2, or if value ≥4, or if preRx=0 or 0.5 use ≥2, or if preRx=1 use ≥3, or if preRx=2 or 3 use ≥4; glucose, urine: If missing preRx use ≥2, or if value ≥4, or if preRx=0 or 0.5 use ≥2, or if preRx=1 use ≥3, or if preRx=2 or 3 use ≥4; protein, urine: If missing preRx use ≥ 2, or if value ≥4, or if preRx=0 or 0.5 use ≥2, or if preRx=1 use ≥3, or if preRx=2 or 3 use ≥4; Red blood cells , urine: If missing preRx use ≥2, or if value ≥4, or if preRx=0 or 0.5 use ≥2, or if preRx=1 use ≥3, or if preRx=2 or 3 use ≥4; white blood cells, urine: If missing preRx use ≥2, or if value ≥4, or if preRx=0 or 0.5 use ≥2, or if preRx=1 use ≥3, or if preRx=2 or 3 use ≥4.
Time frame: Randomization to Days 2, 3, 4, and 12 (±2 days) and at Days 42 and 72 (± 5 days) of follow-up
Population: All participants who received at least 1 dose of study drug. n=number of participants with available measurements
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities in Urinalysis Results During the Treatment Period-Treated Subjects With Available Measurements (Urinalysis) | Glucose, urine (high) (n=1421, 1429) | 160 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities in Urinalysis Results During the Treatment Period-Treated Subjects With Available Measurements (Urinalysis) | Red blood cells, urine (high) (n=441, 385) | 133 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities in Urinalysis Results During the Treatment Period-Treated Subjects With Available Measurements (Urinalysis) | Protein, urine (high) (n=1421, 1430) | 60 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities in Urinalysis Results During the Treatment Period-Treated Subjects With Available Measurements (Urinalysis) | White blood cells, urine (high)(n=441, 386) | 101 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities in Urinalysis Results During the Treatment Period-Treated Subjects With Available Measurements (Urinalysis) | Blood, urine (high) (n=1421, 1430) | 169 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities in Urinalysis Results During the Treatment Period-Treated Subjects With Available Measurements (Urinalysis) | White blood cells, urine (high)(n=441, 386) | 102 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities in Urinalysis Results During the Treatment Period-Treated Subjects With Available Measurements (Urinalysis) | Blood, urine (high) (n=1421, 1430) | 113 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities in Urinalysis Results During the Treatment Period-Treated Subjects With Available Measurements (Urinalysis) | Glucose, urine (high) (n=1421, 1429) | 154 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities in Urinalysis Results During the Treatment Period-Treated Subjects With Available Measurements (Urinalysis) | Protein, urine (high) (n=1421, 1430) | 89 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities in Urinalysis Results During the Treatment Period-Treated Subjects With Available Measurements (Urinalysis) | Red blood cells, urine (high) (n=441, 385) | 116 Participants |
Other Pre-specified
Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements)
preRX=pretreatment; LLN=lower limit of normal; ULN=upper limit of normal; abs=absolute. Hemoglobin (g/dL): \>2 decrease from preRx value or value \<=8; hematocrit (%): \<0.75\*preRx; platelets: \<100\*10\^9 cells/L; erythrocytes (\*10\^6 cells/μL): \<0.75\*preRx; leukocytes: \<0.75\*LLN or \>1.25\*ULN, or if preRx \<LLN, use \<0.8\*preRx or \>ULN if preRx \>ULN use \>1.2\*preRx or \<LLN; abs basophils: \>400/mm\^3; abs eosinophils: \> 0.750\*10\^3 cells/µL; abs lymphocytes: \<0.750\*10\*3 cells/ µL or \>7.50\*10\^3 c/ µL; abs monocytes \> 2000/mm\^3; abs neutrophils: \<1.0\*10\^3 cells/μL; ALP (U/L): \>2\*ULN; ALT, AST (U/L): \>3\*ULN; U/L; bilirubin, direct (mg/dL): \>1.5\*ULN; bilirubin, total (mg/dL): \>2\*ULN; BUN (mg/dL): \>2\*ULN; creatinine (mg/dL): \>1.5\*ULN.
Time frame: Randomization to Days 2, 3, 4, and 12 (±2 days) and at Days 42 and 72 (±5 days) of follow-up
Population: All participants who received at least 1 dose of study drug. n=number of participants with available measurements
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Leukocytes, high (n=1457, 1471) | 193 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Monocytes (absolute), high (n=1448, 1465) | 5 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Erythrocytes, low (n=1368, 1396) | 690 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Neutrophils (absolute), low (n=1448, 1465) | 5 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Basophils (absolute), high (n=1448, 1465) | 2 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Alkaline phosphatase (ALP), high (n=1465, 1476) | 15 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Platelet count, low (n=1413, 1425) | 7 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Alanine aminotransferase (ALT), high (n=1459,1472) | 32 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Eosinophils (absolute), high (n=1448, 1465) | 43 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Aspartate aminotransferase (AST) , high (n=1459,14 | 34 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Leukocytes, low (n=1457, 1471) | 27 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Bilirubin, direct (high) (n=1447,1457) | 87 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Lymphocytes (absolute), low (n=1448, 1465) | 203 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Bilirubin, total (high) (n=1461,1476) | 15 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Hematocrit, low n=(1369, 1396) | 668 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Blood urea nitrogen (BUN) (high)(n=1447,1458) | 15 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Lymphocytes (absolute), high (n=1448, 1465) | 1 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Creatinine (high) (n=1447,1458) | 17 Participants |
| Apixaban, 2.5 mg BID + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Hemoglobin, low (n=1424, 1442) | 1127 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Creatinine (high) (n=1447,1458) | 23 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Hemoglobin, low (n=1424, 1442) | 1178 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Hematocrit, low n=(1369, 1396) | 723 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Platelet count, low (n=1413, 1425) | 5 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Erythrocytes, low (n=1368, 1396) | 735 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Leukocytes, low (n=1457, 1471) | 26 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Leukocytes, high (n=1457, 1471) | 213 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Basophils (absolute), high (n=1448, 1465) | 4 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Eosinophils (absolute), high (n=1448, 1465) | 60 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Lymphocytes (absolute), low (n=1448, 1465) | 215 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Lymphocytes (absolute), high (n=1448, 1465) | 0 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Monocytes (absolute), high (n=1448, 1465) | 2 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Neutrophils (absolute), low (n=1448, 1465) | 2 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Alkaline phosphatase (ALP), high (n=1465, 1476) | 31 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Alanine aminotransferase (ALT), high (n=1459,1472) | 26 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Aspartate aminotransferase (AST) , high (n=1459,14 | 26 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Bilirubin, direct (high) (n=1447,1457) | 76 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Bilirubin, total (high) (n=1461,1476) | 9 Participants |
| Enoxaparin, 40 mg QD + Placebo | Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements) | Blood urea nitrogen (BUN) (high)(n=1447,1458) | 17 Participants |