Pulmonary Embolism, Venous Thrombosis
Conditions
Keywords
Prevention of deep vein thrombosis and pulmonary embolism with acutely ill hospitalized patients
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 within patients hospitalized for acute medical illness, and to learn how apixaban compares to enoxaparin (Lovenox®) for preventing these clots. The safety of apixaban will also be studied.
Interventions
DRUGApixaban
Apixaban: Twice daily, 30 days Placebo: Once daily, 6-14 days
DRUGEnoxaparin
Enoxaparin: Once daily, 6-14 days Placebo: Twice daily, 30 days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* men and non-pregnant, non-breastfeeding women * 40 years or older * hospitalized with congestive heart failure or acute respiratory failure * infection (without septic shock) * acute rheumatic disorder * inflammatory bowel disease
Exclusion criteria
* patients with venous thromboembolism (VTE) * active bleeding or at high risk of bleeding * unable to take oral medication * with diseases requiring ongoing treatment with anticoagulants or antiplatelets other than aspirin at a dose ≤ 165 mg/day.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Composite of Adjudicated Total Venous Thromboembolism (VTE) and VTE-related Death During the Intended Treatment Period - Primary Efficacy Population | Intended Treatment Period | VTE: nonfatal pulmonary embolism (PE), symptomatic deep vein thrombosis (DVT), or asymptomatic proximal DVT detected by ultrasound. VTE-related death: fatal PE or sudden death for which VTE could not be excluded as a cause. Intended Treatment Period=period that started on day of randomization: period ended (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; period ended (for not treated) 32 days after randomization. A bilateral compression ultrasound (CUS) was performed between Days 5 and 14 for detection of asymptomatic proximal DVT unless a symptomatic VTE was confirmed prior. CUS was also performed on Day 30 ± 2 except for those participants who had a confirmed symptomatic VTE or proximal asymptomatic DVT prior to that time. All efficacy events were adjudicated by the Independent Central Adjudication Committee (ICAC). Event rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants). |
| Incidence of Major Bleeding During the Treatment Period in Treated Participants | Day 1, first dose of study drug, to last dose of study drug plus 2 days | Major bleeding was adjudicated by an ICAC using criteria from the International Society on Thrombosis and Hemostasis (ISTH) and was defined as acute clinically overt bleeding: associated with a fall in hemoglobin of 2 grams per deciliter (g/dL) or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 milliliters (mL) or more of whole blood, or bleeding in a critical site or bleeding which is fatal. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants). |
| Incidence of Clinically Relevant Non-Major (CRNM) Bleeding During the Treatment Period in Treated Participants | Day 1, first dose of study drug, to last dose of study drug plus 2 days | Bleeding was adjudicated by an ICAC using criteria from the ISTH. CRNM bleeding: acute clinically overt bleeding compromising hemodynamics; leading to hospitalization; traumatic subcutaneous hematoma; intramuscular hematoma; epistaxis that lasted for more than 5 minutes, was repetitive or led to an intervention; spontaneous gingival bleeding; spontaneous hematuria; macroscopic gastrointestinal hemorrhage (including at least 1 episode of melena or hematemesis, if clinically apparent with positive results on a fecal occult-blood test); rectal blood loss. Treatment Period=includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drugs for bleeding endpoints. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants). |
| Incidence of Composite of Major or Clinically Relevant Non-Major (CRNM) Bleeding During the Treatment Period in Treated Participants | Day 1, first dose of study drug, to last dose of study drug plus 2 days | Bleeding was adjudicated by an ICAC using criteria from the ISTH. Major bleeding: acute clinically overt bleeding: associated with a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 mL or more of whole blood, or bleeding in a critical site or bleeding which is fatal. CRNM bleeding: acute clinically overt bleeding compromising hemodynamics; leading to hospitalization; traumatic subcutaneous hematoma; intramuscular hematoma; epistaxis that lasted for more than 5 minutes, was repetitive or led to an intervention; spontaneous gingival bleeding; spontaneous hematuria; macroscopic gastrointestinal hemorrhage; rectal blood loss. Treatment Period=onset from first dose of study drug through 2 days after last dose of study drugs. Incidence: Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants). |
| Incidence of All Bleeding During the Treatment Period in Treated Participants | Day 1, first dose of drug to last dose of drug plus 2 days | Bleeding was adjudicated by an ICAC using criteria from the ISTH. Treatment Period=includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drugs, for bleeding endpoints. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adjudicated VTE-Related Death With Onset During the Intended Treatment Period in Randomized Participants | Intended Treatment Period | Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE-related death: fatal PE or sudden death for which VTE cannot be excluded as a cause. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants). |
| Incidence of Adjudicated Symptomatic VTE or All-Cause Death With Onset During the Intended Treatment Period | Intended Treatment Period | Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE: nonfatal PE, symptomatic DVT, or asymptomatic proximal DVT detected by ultrasound. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants). |
| Symptomatic Adjudicated VTE or VTE-Related Death With Onset During the Intended Treatment Period | Intended Treatment Period | Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE: nonfatal PE, symptomatic DVT, or asymptomatic proximal DVT detected by ultrasound. VTE-related death: fatal PE or sudden death for which VTE cannot be excluded as a cause. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants). |
| Incidence of All VTE or Major Bleeding or All-Cause Death During the Intended Treatment Period | Intended Treatment Period | Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE: nonfatal PE, symptomatic DVT, or asymptomatic proximal DVT detected by ultrasound. VTE-related death: fatal PE or sudden death for which VTE cannot be excluded as a cause. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants). |
| Incidence of Adjudicated PE With Onset During the Intended Treatment Period | Intended Treatment Period | Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. PE: non-fatal or fatal. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants). |
| Incidence of Adjudicated Non-Fatal PE With Onset During the Intended Treatment Period | Intended Treatment Period | Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants). |
| Incidence of Adjudicated Symptomatic DVT With Onset During the Intended Treatment Period | Intended Treatment Period | Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants). |
| Incidence of Adjudicated Proximal DVT With Onset During the Intended Treatment Period | Intended Treatment Period | Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. A bilateral compression ultrasound (CUS) was performed between Days 5 and 14 for detection of asymptomatic proximal DVT unless a symptomatic VTE was confirmed prior. CUS was also performed on Day 30 ± 2 except for those participants who had a confirmed symptomatic VTE or proximal asymptomatic DVT prior to that time. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants). |
| Incidence of Adjudicated Symptomatic Distal DVT With Onset During the Intended Treatment Period | Intended Treatment Period | Events were adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants). |
| Incidence of Adjudicated Symptomatic Proximal DVT With Onset During the Intended Treatment Period | Intended Treatment Period | Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. A bilateral compression ultrasound (CUS) was performed between Days 5 and 14 for detection of asymptomatic proximal DVT unless a symptomatic VTE was confirmed prior. CUS was also performed on Day 30 ± 2 except for those participants who had a confirmed symptomatic VTE or proximal asymptomatic DVT prior to that time. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants). |
| Incidence of Adjudicated Asymptomatic Proximal DVT With Onset During the Intended Treatment Period | Intended Treatment Period | A bilateral compression ultrasound (CUS) was performed between Days 5 and 14 for detection of asymptomatic proximal DVT unless a symptomatic VTE was confirmed prior. CUS was also performed on Day 30 ± 2 except for those participants who had a confirmed symptomatic VTE or proximal asymptomatic DVT prior to that time. Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants). |
| Incidence of Adjudicated Total VTE and VTE-Related Death During Parenteral Treatment in Key Secondary Efficacy Evaluable Participants | Day 1 to last dose of parenteral study drug plus 1 day | Parenteral study drug=active or placebo enoxaparin. Parenteral treatment: started on the first dose of parenteral study drug and ended the day after the last dose of parenteral study drug. Key Secondary Efficacy population: all who received at least 1 dose of parenteral study drug and: (those without suspected VTE events during Parenteral Treatment) had an adjudicated evaluable ultrasound performed at the end of Parenteral Treatment; or (those with suspected VTE events during Parenteral Treatment) had those suspected VTE events adjudicated as non-events, and had an adjudicated evaluable ultrasound performed at the end of Parenteral Treatment; or had an adjudicated total VTE during Parenteral Treatment; or had an adjudicated VTE-related death during Parenteral Treatment. Event rate (%): n/N\*100 (n=number with observation; N=total secondary efficacy evaluable participants). |
| Mean Change From Baseline in Diastolic Blood Pressure in Treated Participants During Treatment Period | Day 1 to last dose of study drug plus 2 days | Diastolic blood pressure was obtained during Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days. Blood pressure was measured in millimeters of mercury (mmHg) and could have been taken with the participant either sitting, standing, or supine. |
| Mean Change From Baseline in Systolic Blood Pressure in Treated Participants During Treatment Period | Day 1 to last dose of study drug plus 2 days | Systolic blood pressure was obtained during Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days. Blood pressure was measured in millimeters of mercury (mmHg) and could have been taken either sitting, standing, or supine. |
| Mean Change From Baseline in Heart Rate in Treated Participants | Day 1 to last dose of study drug plus 2 days | Heart Rate was obtained during Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days. Heart rate was measured in beats per minute (bpm) and could have been taken with participants either sitting, standing, or supine. |
| Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants | Day 1 to last dose of study drug plus 2 days | Lower limit of normal (LLN). Upper limit of normal (ULN). Pre-therapy (PreRx). Absolute (Abs) neutrophil count, bands + neutrophils (ANC). Cells per microliter (c/µL). Grams per deciliter (g/dL). Cells per Liter (c/L). Millimeter (MM). Absolute (Abs). Hemoglobin: \>2 g/dL decrease compared to PreRx value or value \<=8 g/dL; Hematocrit: \<0.75\*PreRx; Erythrocytes: \<0.75\*PreRx c/µL; Leukocytes: \<0.75\*LLN or \> 1.25\*ULN, if PreRx \<LLN then use \<0.8\*PreRx or \>ULN, if PreRx \>ULN then use \>1.2\*PreRx or \< LLN; Platelet count: \< 100\*10\^9 c/L; ANC: \< 1.00\*10\^3 c/µL; Abs eosinophils: \> 0.75\*10\^3 c/µL; Abs Basophils: \> 400/MM\^3; Abs Monocytes \> 2000/MM\^3; Abs Lymphocytes: \< 0.750\*10\*3 c/ µL or \> 7.5\*10\^3 c/ µL. Samples were obtained at Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days. |
| Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants | Day 1 to last dose of study drug plus 2 days | Bicarbonate milliequivalents/Liter (mEq/L) Low/High: \< 0.75\*LLN or \> 1.25\*ULN, or if PreRx \< LLN then use \< 0.75\* PreRx or \> ULN if PreRx \> ULN then use \> 1.25\*PreRx or \< LLN; Serum Calcium mg/dL Low/High: \< 0.8\*LLN or \> 1.2\*ULN, or if PreRx \< LLN then use \< 0.75\*PreRx or \> ULN if PreRx \> ULN then use \> 1.25\*PreRx or \< LLN; Serum Chloride mEq/L: \< 0.9\*LLN or \> 1.1\*ULN, or if PreRx \< LLN then use \< 0.9\*PreRx or \> ULN if PreRx \> ULN then use \> 1.1\*PreRx or \< LLN; Serum Potassium mEq/L: \< 0.9\*LLN or \> 1.1\*ULN, or if PreRx \< LLN then use \< 0.9\*PreRx or \> ULN if PreRx \> ULN then use \> 1.1\*PreRx or \< LLN; Serum Sodium mEq/L: \< 0.95\*LLN or \> 1.05\*ULN, or if PreRx \< LLN then use \< 0.95\*PreRx or \> ULN if PreRx \> ULN then use \> 1.05\*PreRx or \< LLN. Samples obtained at Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days. |
| Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants | Day 1 to last dose of study drug plus 2 days | Blood urea nitrogen (BUN), milligrams/deciliter (mg/dL), units per liter (U/L). BUN mg/dL \> 1.5\*ULN; Creatinine mg/dL: \> 1.5\*ULN; Alanine aminotransferase (ALT) U/L: \> 3\*ULN; Aspartate aminotransferase (AST) U/L: \> 3\*ULN; Alkaline phosphatase U/L: \> 2\*ULN; Bilirubin Direct mg/dL: \> 1.5\*ULN; Bilirubin Total mg/dL: \> 2\*ULN. Samples for laboratories obtained at Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days. |
| Number of Participants With Marked Abnormalities in Glucose, Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests During the Treatment Period in Treated Participants | Day 1 to last dose of study drug plus 2 days | Creatine kinase High: \>5\*ULN Units/Liter (U/L); Total Protein High/Low: \< 0.9 \*LLN or \> 1.1\*ULN, or if PreRx \< LLN then use 0.9\* PreRx or \> ULN if PreRx \> ULN then use 1.1 \*PreRx or \<LLN; Uric acid High: \> 1.5\* ULN, or if PreRx \> ULN then use \> 2 \*PreRx. Glucose Fasting: \<0.9\*LLN or \> 1.5\*ULN or if PreRx \< LLN then use \< 0.8\*PreRx or \> ULN, if PreRx \> ULN then use \>2.0\*PreRx. Samples obtained at Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) ± 2days. |
| Incidence of Events of Special Interest of Adjudicated Myocardial Infarction, Stroke, and Thrombocytopenia During the Treatment Period in Treated Participants | Day 1 to last dose of study drug plus 2 days | Events of Special Interest include: adjudicated thrombocytopenia, adjudicated myocardial infarction (MI), adjudicated stroke, and adjudicated MI or stroke. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants). Treatment Period includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drugs. |
| Number of Participants With Events of Special Interest for Liver Function and Neurology During Treatment Period in Treated Participants With Available Measurements | Day 1 to last dose of study drug plus 2 days (AEs) and plus 30 days (SAEs) | Special interest include: liver function test increases, AEs related to liver function, and neurologic AEs. Treatment Period includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drug when summarizing AEs and through 30 days after the last dose when summarizing SAEs. |
| Number of Participants With Liver-Related Elevations During the Treatment Period in Treated Participants | Day 1 to last dose of study drug plus 2 days | Liver function tests: Alanine aminotransferase (ALT) U/L; Aspartate aminotransferase (AST) U/L; Alkaline phosphatase U/L; Total Bilirubin (TBili) mg/dL. Elevations consist of \>3\*Upper Limit of Normal (ULN) for ALT and AST and elevation of \>2\*ULN for Bilirubin. |
| Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Deaths, and Discontinuations Due to AEs During the Treatment Period in Treated Participants | Day 1, first dose of study drug, to last dose of study drug plus 2 days (AEs), plus 30 days (SAEs, Deaths) | Treatment Period=includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drugs for AEs, and 30 days after last dose of study drugs for SAEs and deaths. |
| Incidence of Adjudicated Total VTE and VTE-Related Death During Parenteral Treatment in Secondary Efficacy Evaluable Participants | Day 1 to last dose of parenteral study drug plus 1 day | Parenteral study drug=active or placebo enoxaparin. Parenteral treatment: started on the first dose of parenteral study drug and ended the day after the last dose of parenteral study drug. Secondary Efficacy Evaluable includes those who had an adjudicated, evaluable ultrasound at end of parenteral treatment and for those with a suspected symptomatic event, the result of the adjudication for the symptomatic event was not inadequate; or those with an adjudicated event that was part of the composite endpoint.. Event rate (%): n/N\*100 (n=number with observation; N=total secondary efficacy evaluable participants). |
| Incidence of Adjudicated Total VTE or All-Cause Death With Onset During the Intended Treatment Period | Intended Treatment Period | Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE: nonfatal (N-F) PE, symptomatic DVT, or asymptomatic proximal DVT detected by ultrasound. VTE-related death: fatal PE or sudden death for which VTE cannot be excluded as a cause. All-Cause Death (A-C Death). Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants). |
| Incidence of Adjudicated Proximal DVT, Non-Fatal PE or All-Cause Death With Onset During the Intended Treatment Period | Intended Treatment Period | Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants). |
| Incidence of Adjudicated Proximal DVT, Non-Fatal PE or VTE-Related Death, With Onset During the Intended Treatment Period | Intended Treatment Period | Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE-related death: fatal PE or sudden death for which VTE cannot be excluded as a cause. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants). |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Colombia, Czechia, Denmark, France, Germany, Hong Kong, Hungary, India, Israel, Italy, Malaysia, Mexico, Netherlands, Norway, Peru, Philippines, Poland, Russia, Singapore, South Africa, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
First patient, first visit was June 2007 and last patient, last visit was May 2011. Acutely ill patients who had been hospitalized and had an expected hospitalization of an additional 3 or more days after randomization were enrolled.
Pre-assignment details
6758 enrolled; 6528 randomized to treatment. Reasons for non-randomization: 2 Adverse event (AE); 34 withdrew consent; 1 death; 3 poor/non-compliance; 162 no longer met study criteria; 2 administrative reason by Sponsor; 26 other reasons.
Participants by arm
| Arm | Count |
|---|---|
| Apixaban 2.5 mg Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days. | 3,255 |
| Enoxaparin 40 mg Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days. | 3,273 |
| Total | 6,528 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative reason by Sponsor | 1 | 0 |
| Overall Study | Adverse Event | 284 | 260 |
| Overall Study | Death | 40 | 47 |
| Overall Study | Lost to Follow-up | 72 | 71 |
| Overall Study | No longer met criteria | 41 | 37 |
| Overall Study | non-specified | 29 | 38 |
| Overall Study | Poor/Non-compliance | 46 | 33 |
| Overall Study | treated for 1 day; missing status/reason | 1 | 0 |
| Overall Study | Withdrawal by Subject | 299 | 271 |
Baseline characteristics
| Characteristic | Apixaban 2.5 mg | Enoxaparin 40 mg | Total |
|---|---|---|---|
| Age, Continuous | 68.0 years | 67.0 years | 67.0 years |
| Age, Customized >= 75 years | 964 participants | 978 participants | 1942 participants |
| Age, Customized Greater than, equal to (>=) 65 and < 75 years | 890 participants | 884 participants | 1774 participants |
| Age, Customized Less than (<) 65 years | 1401 participants | 1411 participants | 2812 participants |
| Participants with Risk Factors Chronic Heart Failure | 1531 participants | 1537 participants | 3068 participants |
| Participants with Risk Factors Estrogenic Hormone Therapy | 49 participants | 27 participants | 76 participants |
| Participants with Risk Factors History of Malignancy | 312 participants | 320 participants | 632 participants |
| Participants with Risk Factors Previous Venous Thromboembolism (VTE) | 141 participants | 124 participants | 265 participants |
| Region of Enrollment Argentina | 78 participants | 77 participants | 155 participants |
| Region of Enrollment Australia | 51 participants | 49 participants | 100 participants |
| Region of Enrollment Austria | 5 participants | 7 participants | 12 participants |
| Region of Enrollment Belgium | 21 participants | 22 participants | 43 participants |
| Region of Enrollment Brazil | 41 participants | 45 participants | 86 participants |
| Region of Enrollment Canada | 45 participants | 47 participants | 92 participants |
| Region of Enrollment Chile | 65 participants | 65 participants | 130 participants |
| Region of Enrollment Colombia | 10 participants | 14 participants | 24 participants |
| Region of Enrollment Czech Republic | 53 participants | 56 participants | 109 participants |
| Region of Enrollment Denmark | 49 participants | 54 participants | 103 participants |
| Region of Enrollment France | 203 participants | 200 participants | 403 participants |
| Region of Enrollment Germany | 35 participants | 32 participants | 67 participants |
| Region of Enrollment Hong Kong | 26 participants | 26 participants | 52 participants |
| Region of Enrollment Hungary | 18 participants | 16 participants | 34 participants |
| Region of Enrollment India | 198 participants | 202 participants | 400 participants |
| Region of Enrollment Israel | 168 participants | 168 participants | 336 participants |
| Region of Enrollment Italy | 35 participants | 34 participants | 69 participants |
| Region of Enrollment Korea, Republic of | 33 participants | 33 participants | 66 participants |
| Region of Enrollment Malaysia | 9 participants | 11 participants | 20 participants |
| Region of Enrollment Mexico | 58 participants | 59 participants | 117 participants |
| Region of Enrollment Netherlands | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Norway | 3 participants | 2 participants | 5 participants |
| Region of Enrollment Peru | 119 participants | 121 participants | 240 participants |
| Region of Enrollment Philippines | 22 participants | 22 participants | 44 participants |
| Region of Enrollment Poland | 57 participants | 60 participants | 117 participants |
| Region of Enrollment Russian Federation | 632 participants | 632 participants | 1264 participants |
| Region of Enrollment Singapore | 8 participants | 12 participants | 20 participants |
| Region of Enrollment South Africa | 52 participants | 48 participants | 100 participants |
| Region of Enrollment Spain | 51 participants | 50 participants | 101 participants |
| Region of Enrollment Sweden | 2 participants | 2 participants | 4 participants |
| Region of Enrollment Taiwan | 8 participants | 7 participants | 15 participants |
| Region of Enrollment Turkey | 9 participants | 10 participants | 19 participants |
| Region of Enrollment Ukraine | 270 participants | 276 participants | 546 participants |
| Region of Enrollment United Kingdom | 195 participants | 194 participants | 389 participants |
| Region of Enrollment United States | 625 participants | 620 participants | 1245 participants |
| Sex: Female, Male Female | 1629 Participants | 1696 Participants | 3325 Participants |
| Sex: Female, Male Male | 1626 Participants | 1577 Participants | 3203 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 3,184 | 0 / 3,217 |
| serious Total, serious adverse events | 611 / 3,184 | 601 / 3,217 |
Outcome results
Primary
Incidence of All Bleeding During the Treatment Period in Treated Participants
Bleeding was adjudicated by an ICAC using criteria from the ISTH. Treatment Period=includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drugs, for bleeding endpoints. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Day 1, first dose of drug to last dose of drug plus 2 days
Population: Participants who received at least one dose of study drug were analyzed (As Treated population). Participants were categorized to the group to which they were randomized, unless the same incorrect treatment was received throughout the study; in such case, the As Treated were equal to the treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Incidence of All Bleeding During the Treatment Period in Treated Participants | 7.73 Event Rate (%) |
| Enoxaparin 40 mg | Incidence of All Bleeding During the Treatment Period in Treated Participants | 6.81 Event Rate (%) |
95% CI: [-0.4, 2.14]
Primary
Incidence of Clinically Relevant Non-Major (CRNM) Bleeding During the Treatment Period in Treated Participants
Bleeding was adjudicated by an ICAC using criteria from the ISTH. CRNM bleeding: acute clinically overt bleeding compromising hemodynamics; leading to hospitalization; traumatic subcutaneous hematoma; intramuscular hematoma; epistaxis that lasted for more than 5 minutes, was repetitive or led to an intervention; spontaneous gingival bleeding; spontaneous hematuria; macroscopic gastrointestinal hemorrhage (including at least 1 episode of melena or hematemesis, if clinically apparent with positive results on a fecal occult-blood test); rectal blood loss. Treatment Period=includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drugs for bleeding endpoints. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Day 1, first dose of study drug, to last dose of study drug plus 2 days
Population: Participants who received at least one dose of study drug were analyzed (As Treated population). Participants were categorized to the group to which they were randomized, unless the same incorrect treatment was received throughout the study; in such case, the As Treated were equal to the treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Incidence of Clinically Relevant Non-Major (CRNM) Bleeding During the Treatment Period in Treated Participants | 2.26 Event Rate (%): |
| Enoxaparin 40 mg | Incidence of Clinically Relevant Non-Major (CRNM) Bleeding During the Treatment Period in Treated Participants | 1.90 Event Rate (%): |
Comparison: Adjusted difference of event rates takes the stratification factor into consideration: previous VTE (yes, no) and active or previous cancer (yes, no).95% CI: [-0.33, 1.06]
Primary
Incidence of Composite of Adjudicated Total Venous Thromboembolism (VTE) and VTE-related Death During the Intended Treatment Period - Primary Efficacy Population
VTE: nonfatal pulmonary embolism (PE), symptomatic deep vein thrombosis (DVT), or asymptomatic proximal DVT detected by ultrasound. VTE-related death: fatal PE or sudden death for which VTE could not be excluded as a cause. Intended Treatment Period=period that started on day of randomization: period ended (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; period ended (for not treated) 32 days after randomization. A bilateral compression ultrasound (CUS) was performed between Days 5 and 14 for detection of asymptomatic proximal DVT unless a symptomatic VTE was confirmed prior. CUS was also performed on Day 30 ± 2 except for those participants who had a confirmed symptomatic VTE or proximal asymptomatic DVT prior to that time. All efficacy events were adjudicated by the Independent Central Adjudication Committee (ICAC). Event rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Population: Those randomized (without suspected VTE) who had an adjudicated and evaluable ultrasound at end of intended treatment; or (with suspected VTE) had VTE events adjudicated as non-events and had an adjudicated and evaluable ultrasound at end of intended treatment, or had an adjudicated total VTE-related death.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Incidence of Composite of Adjudicated Total Venous Thromboembolism (VTE) and VTE-related Death During the Intended Treatment Period - Primary Efficacy Population | 2.71 Event rate (%) |
| Enoxaparin 40 mg | Incidence of Composite of Adjudicated Total Venous Thromboembolism (VTE) and VTE-related Death During the Intended Treatment Period - Primary Efficacy Population | 3.06 Event rate (%) |
Comparison: To conclude superiority of apixaban versus enoxaparin on the primary efficacy endpoint, the upper bound of the two-sided 95.004% confidence interval (CI) for the relative risk (pa/ pe) must be less than 1.p-value: 0.436495% CI: [0.62, 1.23]Mantel Haenszel
95% CI: [-1.37, 0.59]
Primary
Incidence of Composite of Major or Clinically Relevant Non-Major (CRNM) Bleeding During the Treatment Period in Treated Participants
Bleeding was adjudicated by an ICAC using criteria from the ISTH. Major bleeding: acute clinically overt bleeding: associated with a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 mL or more of whole blood, or bleeding in a critical site or bleeding which is fatal. CRNM bleeding: acute clinically overt bleeding compromising hemodynamics; leading to hospitalization; traumatic subcutaneous hematoma; intramuscular hematoma; epistaxis that lasted for more than 5 minutes, was repetitive or led to an intervention; spontaneous gingival bleeding; spontaneous hematuria; macroscopic gastrointestinal hemorrhage; rectal blood loss. Treatment Period=onset from first dose of study drug through 2 days after last dose of study drugs. Incidence: Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Day 1, first dose of study drug, to last dose of study drug plus 2 days
Population: Participants who received at least one dose of study drug were analyzed (As Treated population). Participants were categorized to the group to which they were randomized, unless the same incorrect treatment was received throughout the study; in such case, the As Treated were equal to the treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Incidence of Composite of Major or Clinically Relevant Non-Major (CRNM) Bleeding During the Treatment Period in Treated Participants | 2.67 Event Rate (%) |
| Enoxaparin 40 mg | Incidence of Composite of Major or Clinically Relevant Non-Major (CRNM) Bleeding During the Treatment Period in Treated Participants | 2.08 Event Rate (%) |
Comparison: Adjusted difference of event rates takes the stratification factor into consideration: previous VTE (yes, no) and active or previous cancer (yes, no).95% CI: [-16, 1.33]
Primary
Incidence of Major Bleeding During the Treatment Period in Treated Participants
Major bleeding was adjudicated by an ICAC using criteria from the International Society on Thrombosis and Hemostasis (ISTH) and was defined as acute clinically overt bleeding: associated with a fall in hemoglobin of 2 grams per deciliter (g/dL) or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 milliliters (mL) or more of whole blood, or bleeding in a critical site or bleeding which is fatal. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Day 1, first dose of study drug, to last dose of study drug plus 2 days
Population: Participants who received at least one dose of study drug were analyzed (As Treated population). Participants were categorized to the group to which they were randomized, unless the same incorrect treatment was received throughout the study; in such case, the As Treated were equal to the treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Incidence of Major Bleeding During the Treatment Period in Treated Participants | 0.47 Event Rate (%) |
| Enoxaparin 40 mg | Incidence of Major Bleeding During the Treatment Period in Treated Participants | 0.19 Event Rate (%) |
Comparison: Adjusted difference of event rates takes the stratification factor into consideration: previous VTE (yes, no) and active or previous cancer (yes, no).p-value: 0.043795% CI: [0.01, 0.57]Mantel Haenszel
Secondary
Incidence of Adjudicated Asymptomatic Proximal DVT With Onset During the Intended Treatment Period
A bilateral compression ultrasound (CUS) was performed between Days 5 and 14 for detection of asymptomatic proximal DVT unless a symptomatic VTE was confirmed prior. CUS was also performed on Day 30 ± 2 except for those participants who had a confirmed symptomatic VTE or proximal asymptomatic DVT prior to that time. Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Population: Those randomized with adjudicated and evaluable ultrasound at the end of the intended treatment period; for those with a suspected symptomatic event, the adjudication result was not inadequate; includes all those randomized who have an adjudicated event associated with the endpoint during Intended Treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Incidence of Adjudicated Asymptomatic Proximal DVT With Onset During the Intended Treatment Period | 2.36 Event Rate (%) |
| Enoxaparin 40 mg | Incidence of Adjudicated Asymptomatic Proximal DVT With Onset During the Intended Treatment Period | 2.12 Event Rate (%) |
95% CI: [0.74, 1.61]
95% CI: [-0.66, 1.07]
Secondary
Incidence of Adjudicated Non-Fatal PE With Onset During the Intended Treatment Period
Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Population: Randomized participants except those with an inadequate assessment for symptomatic events that are part of the endpoint during the intended treatment were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Incidence of Adjudicated Non-Fatal PE With Onset During the Intended Treatment Period | 0.22 Event Rate (%) |
| Enoxaparin 40 mg | Incidence of Adjudicated Non-Fatal PE With Onset During the Intended Treatment Period | 0.24 Event Rate (%) |
95% CI: [0.32, 2.43]
95% CI: [-0.26, 0.2]
Secondary
Incidence of Adjudicated PE With Onset During the Intended Treatment Period
Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. PE: non-fatal or fatal. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Population: Randomized participants except those with an inadequate assessment for symptomatic events that are part of the endpoint during the intended treatment were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Incidence of Adjudicated PE With Onset During the Intended Treatment Period | 0.22 Event Rate (%) |
| Enoxaparin 40 mg | Incidence of Adjudicated PE With Onset During the Intended Treatment Period | 0.24 Event Rate (%) |
95% CI: [0.32, 2.43]
95% CI: [-0.26, 0.2]
Secondary
Incidence of Adjudicated Proximal DVT, Non-Fatal PE or All-Cause Death With Onset During the Intended Treatment Period
Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Population: Those randomized with adjudicated and evaluable ultrasound at the end of the intended treatment period; for those with a suspected symptomatic event, the adjudication result was not inadequate; includes all those randomized who have an adjudicated event associated with the endpoint during Intended Treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Incidence of Adjudicated Proximal DVT, Non-Fatal PE or All-Cause Death With Onset During the Intended Treatment Period | 6.44 Event Rate (%) |
| Enoxaparin 40 mg | Incidence of Adjudicated Proximal DVT, Non-Fatal PE or All-Cause Death With Onset During the Intended Treatment Period | 6.50 Event Rate (%) |
95% CI: [0.79, 1.22]
95% CI: [-1.52, 1.29]
Secondary
Incidence of Adjudicated Proximal DVT, Non-Fatal PE or VTE-Related Death, With Onset During the Intended Treatment Period
Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE-related death: fatal PE or sudden death for which VTE cannot be excluded as a cause. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Population: Those randomized with adjudicated and evaluable ultrasound at the end of the intended treatment period; for those with a suspected symptomatic event, the adjudication result was not inadequate; includes all those randomized who have an adjudicated event associated with the endpoint during Intended Treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Incidence of Adjudicated Proximal DVT, Non-Fatal PE or VTE-Related Death, With Onset During the Intended Treatment Period | 2.71 Event Rate (%) |
| Enoxaparin 40 mg | Incidence of Adjudicated Proximal DVT, Non-Fatal PE or VTE-Related Death, With Onset During the Intended Treatment Period | 2.93 Event Rate (%) |
95% CI: [0.65, 1.29]
95% CI: [-1.23, 0.71]
Secondary
Incidence of Adjudicated Proximal DVT With Onset During the Intended Treatment Period
Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. A bilateral compression ultrasound (CUS) was performed between Days 5 and 14 for detection of asymptomatic proximal DVT unless a symptomatic VTE was confirmed prior. CUS was also performed on Day 30 ± 2 except for those participants who had a confirmed symptomatic VTE or proximal asymptomatic DVT prior to that time. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Population: Those randomized with adjudicated and evaluable ultrasound at the end of the intended treatment period; for those with a suspected symptomatic event, the adjudication result was not inadequate; includes all those randomized who have an adjudicated event associated with the endpoint during Intended Treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Incidence of Adjudicated Proximal DVT With Onset During the Intended Treatment Period | 2.40 Event Rate (%) |
| Enoxaparin 40 mg | Incidence of Adjudicated Proximal DVT With Onset During the Intended Treatment Period | 2.50 Event Rate (%) |
95% CI: [0.65, 1.37]
95% CI: [-1.04, 0.76]
Secondary
Incidence of Adjudicated Symptomatic Distal DVT With Onset During the Intended Treatment Period
Events were adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Population: Randomized participants, except those with an inadequate assessment for symptomatic events that are part of the endpoint during the intended treatment period, were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Incidence of Adjudicated Symptomatic Distal DVT With Onset During the Intended Treatment Period | 0.00 Event Rate (%) |
| Enoxaparin 40 mg | Incidence of Adjudicated Symptomatic Distal DVT With Onset During the Intended Treatment Period | 0.15 Event Rate (%) |
Comparison: Note: Relative risk was not estimable (0.0); only risk difference could be estimated.95% CI: [-0.29, -0.02]
Secondary
Incidence of Adjudicated Symptomatic DVT With Onset During the Intended Treatment Period
Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Population: Randomized participants except those with an inadequate assessment for symptomatic events that are part of the endpoint during the intended treatment were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Incidence of Adjudicated Symptomatic DVT With Onset During the Intended Treatment Period | 0.15 Event Rate (%) |
| Enoxaparin 40 mg | Incidence of Adjudicated Symptomatic DVT With Onset During the Intended Treatment Period | 0.49 Event Rate (%) |
95% CI: [0.11, 0.83]
95% CI: [-0.62, -0.07]
Secondary
Incidence of Adjudicated Symptomatic Proximal DVT With Onset During the Intended Treatment Period
Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. A bilateral compression ultrasound (CUS) was performed between Days 5 and 14 for detection of asymptomatic proximal DVT unless a symptomatic VTE was confirmed prior. CUS was also performed on Day 30 ± 2 except for those participants who had a confirmed symptomatic VTE or proximal asymptomatic DVT prior to that time. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Population: Randomized participants, except those with an inadequate assessment for symptomatic events that are part of the endpoint during the intended treatment, were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Incidence of Adjudicated Symptomatic Proximal DVT With Onset During the Intended Treatment Period | 0.15 Event Rate (%) |
| Enoxaparin 40 mg | Incidence of Adjudicated Symptomatic Proximal DVT With Onset During the Intended Treatment Period | 0.37 Event Rate (%) |
95% CI: [0.14, 1.16]
95% CI: [-0.47, 0.03]
Secondary
Incidence of Adjudicated Symptomatic VTE or All-Cause Death With Onset During the Intended Treatment Period
Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE: nonfatal PE, symptomatic DVT, or asymptomatic proximal DVT detected by ultrasound. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Population: Randomized participants except those with an inadequate assessment for symptomatic events that are part of the endpoint during the intended treatment were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Incidence of Adjudicated Symptomatic VTE or All-Cause Death With Onset During the Intended Treatment Period | 3.11 Event Rate (%) |
| Enoxaparin 40 mg | Incidence of Adjudicated Symptomatic VTE or All-Cause Death With Onset During the Intended Treatment Period | 3.46 Event Rate (%) |
95% CI: [0.68, 1.16]
95% CI: [-1.25, 0.48]
Secondary
Incidence of Adjudicated Total VTE and VTE-Related Death During Parenteral Treatment in Key Secondary Efficacy Evaluable Participants
Parenteral study drug=active or placebo enoxaparin. Parenteral treatment: started on the first dose of parenteral study drug and ended the day after the last dose of parenteral study drug. Key Secondary Efficacy population: all who received at least 1 dose of parenteral study drug and: (those without suspected VTE events during Parenteral Treatment) had an adjudicated evaluable ultrasound performed at the end of Parenteral Treatment; or (those with suspected VTE events during Parenteral Treatment) had those suspected VTE events adjudicated as non-events, and had an adjudicated evaluable ultrasound performed at the end of Parenteral Treatment; or had an adjudicated total VTE during Parenteral Treatment; or had an adjudicated VTE-related death during Parenteral Treatment. Event rate (%): n/N\*100 (n=number with observation; N=total secondary efficacy evaluable participants).
Time frame: Day 1 to last dose of parenteral study drug plus 1 day
Population: Those randomized (without suspected VTE) who had an adjudicated and evaluable ultrasound at end of parenteral treatment; or (with suspected VTE) had VTE events adjudicated as non-events and had adjudicated and evaluable ultrasound at end of parenteral treatment, or had an adjudicated VTE-related death during the Parenteral Treatment Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Incidence of Adjudicated Total VTE and VTE-Related Death During Parenteral Treatment in Key Secondary Efficacy Evaluable Participants | 1.73 Event rate (%) |
| Enoxaparin 40 mg | Incidence of Adjudicated Total VTE and VTE-Related Death During Parenteral Treatment in Key Secondary Efficacy Evaluable Participants | 1.61 Event rate (%) |
Comparison: Formal testing of noninferiority for the key secondary efficacy endpoint was not performed since the superiority of the primary efficacy endpoint was not demonstrated.95% CI: [0.69, 1.63]
95% CI: [-0.61, 0.81]
Secondary
Incidence of Adjudicated Total VTE and VTE-Related Death During Parenteral Treatment in Secondary Efficacy Evaluable Participants
Parenteral study drug=active or placebo enoxaparin. Parenteral treatment: started on the first dose of parenteral study drug and ended the day after the last dose of parenteral study drug. Secondary Efficacy Evaluable includes those who had an adjudicated, evaluable ultrasound at end of parenteral treatment and for those with a suspected symptomatic event, the result of the adjudication for the symptomatic event was not inadequate; or those with an adjudicated event that was part of the composite endpoint.. Event rate (%): n/N\*100 (n=number with observation; N=total secondary efficacy evaluable participants).
Time frame: Day 1 to last dose of parenteral study drug plus 1 day
Population: Secondary Efficacy Evaluable includes those who have an adjudicated, evaluable ultrasound at end of parenteral treatment and for those with a suspected symptomatic event, the result of the adjudication for the symptomatic event is not inadequate; or those with an adjudicated event that is part of the composite endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Incidence of Adjudicated Total VTE and VTE-Related Death During Parenteral Treatment in Secondary Efficacy Evaluable Participants | 1.66 Event Rate (%) |
| Enoxaparin 40 mg | Incidence of Adjudicated Total VTE and VTE-Related Death During Parenteral Treatment in Secondary Efficacy Evaluable Participants | 1.51 Event Rate (%) |
95% CI: [0.7, 1.71]
95% CI: [-0.57, 0.85]
Secondary
Incidence of Adjudicated Total VTE or All-Cause Death With Onset During the Intended Treatment Period
Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE: nonfatal (N-F) PE, symptomatic DVT, or asymptomatic proximal DVT detected by ultrasound. VTE-related death: fatal PE or sudden death for which VTE cannot be excluded as a cause. All-Cause Death (A-C Death). Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Population: Those randomized with adjudicated and evaluable ultrasound at the end of the intended treatment period; for those with a suspected symptomatic event, the adjudication result was not inadequate; includes all those randomized who have an adjudicated event associated with the endpoint during Intended Treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Incidence of Adjudicated Total VTE or All-Cause Death With Onset During the Intended Treatment Period | 6.44 Event Rate (%) |
| Enoxaparin 40 mg | Incidence of Adjudicated Total VTE or All-Cause Death With Onset During the Intended Treatment Period | 6.63 Event Rate (%) |
95% CI: [0.78, 1.2]
95% CI: [-1.65, 1.17]
Secondary
Incidence of Adjudicated VTE-Related Death With Onset During the Intended Treatment Period in Randomized Participants
Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE-related death: fatal PE or sudden death for which VTE cannot be excluded as a cause. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Population: All Randomized Participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Incidence of Adjudicated VTE-Related Death With Onset During the Intended Treatment Period in Randomized Participants | 0.06 Event Rate (%) |
| Enoxaparin 40 mg | Incidence of Adjudicated VTE-Related Death With Onset During the Intended Treatment Period in Randomized Participants | 0.09 Event Rate (%) |
95% CI: [0.11, 4.05]
95% CI: [-0.16, 0.1]
Secondary
Incidence of All VTE or Major Bleeding or All-Cause Death During the Intended Treatment Period
Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE: nonfatal PE, symptomatic DVT, or asymptomatic proximal DVT detected by ultrasound. VTE-related death: fatal PE or sudden death for which VTE cannot be excluded as a cause. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Population: Those randomized with adjudicated and evaluable ultrasound at the end of the intended treatment period; for those with a suspected symptomatic event, the adjudication result was not inadequate; includes all those randomized who have an adjudicated event associated with the endpoint during Intended Treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Incidence of All VTE or Major Bleeding or All-Cause Death During the Intended Treatment Period | 7.16 Event Rate (%) |
| Enoxaparin 40 mg | Incidence of All VTE or Major Bleeding or All-Cause Death During the Intended Treatment Period | 6.83 Event Rate (%) |
95% CI: [0.84, 1.28]
95% CI: [-1.18, 1.73]
Secondary
Incidence of Events of Special Interest of Adjudicated Myocardial Infarction, Stroke, and Thrombocytopenia During the Treatment Period in Treated Participants
Events of Special Interest include: adjudicated thrombocytopenia, adjudicated myocardial infarction (MI), adjudicated stroke, and adjudicated MI or stroke. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants). Treatment Period includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drugs.
Time frame: Day 1 to last dose of study drug plus 2 days
Population: MI and thrombocytopenia categories: participants who received at least one dose of study drug. MI or stroke category: treated participants except those who did not have MI and had an inadequate assessment for stroke. Stroke category: treated participants except those with an inadequate assessment for stroke during the treatment period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban 2.5 mg | Incidence of Events of Special Interest of Adjudicated Myocardial Infarction, Stroke, and Thrombocytopenia During the Treatment Period in Treated Participants | MI or stoke (N=3183, 3216) | 0.38 Event Rate (%) |
| Apixaban 2.5 mg | Incidence of Events of Special Interest of Adjudicated Myocardial Infarction, Stroke, and Thrombocytopenia During the Treatment Period in Treated Participants | MI (N=3184, 3217) | 0.22 Event Rate (%) |
| Apixaban 2.5 mg | Incidence of Events of Special Interest of Adjudicated Myocardial Infarction, Stroke, and Thrombocytopenia During the Treatment Period in Treated Participants | Stroke (N=3183, 3216) | 0.16 Event Rate (%) |
| Apixaban 2.5 mg | Incidence of Events of Special Interest of Adjudicated Myocardial Infarction, Stroke, and Thrombocytopenia During the Treatment Period in Treated Participants | Thrombocytopenia (N=3184, 3217) | 0.19 Event Rate (%) |
| Enoxaparin 40 mg | Incidence of Events of Special Interest of Adjudicated Myocardial Infarction, Stroke, and Thrombocytopenia During the Treatment Period in Treated Participants | Thrombocytopenia (N=3184, 3217) | 0.09 Event Rate (%) |
| Enoxaparin 40 mg | Incidence of Events of Special Interest of Adjudicated Myocardial Infarction, Stroke, and Thrombocytopenia During the Treatment Period in Treated Participants | MI or stoke (N=3183, 3216) | 0.37 Event Rate (%) |
| Enoxaparin 40 mg | Incidence of Events of Special Interest of Adjudicated Myocardial Infarction, Stroke, and Thrombocytopenia During the Treatment Period in Treated Participants | Stroke (N=3183, 3216) | 0.25 Event Rate (%) |
| Enoxaparin 40 mg | Incidence of Events of Special Interest of Adjudicated Myocardial Infarction, Stroke, and Thrombocytopenia During the Treatment Period in Treated Participants | MI (N=3184, 3217) | 0.12 Event Rate (%) |
Comparison: Adjusted difference in event rates in MI or stroke.95% CI: [-0.3, 0.29]
Comparison: Adjusted difference of event rates for myocardial infarction.95% CI: [-0.11, 0.3]
Comparison: Adjusted difference in event rates for stroke.95% CI: [-0.32, 0.12]
Comparison: Adjusted difference of event rates in thrombocytopenia.95% CI: [-0.09, 0.28]
Secondary
Mean Change From Baseline in Diastolic Blood Pressure in Treated Participants During Treatment Period
Diastolic blood pressure was obtained during Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days. Blood pressure was measured in millimeters of mercury (mmHg) and could have been taken with the participant either sitting, standing, or supine.
Time frame: Day 1 to last dose of study drug plus 2 days
Population: Participants who received at least one dose of study drug, had a baseline value, and had a value on the day specified were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Apixaban 2.5 mg | Mean Change From Baseline in Diastolic Blood Pressure in Treated Participants During Treatment Period | Day 30 of Treatment + 2 (N=2227,2301) | 0.0 mmHg | Standard Deviation 12.91 |
| Apixaban 2.5 mg | Mean Change From Baseline in Diastolic Blood Pressure in Treated Participants During Treatment Period | Day of Discharge from Hospital (N=1607, 1625) | -1.0 mmHg | Standard Deviation 12.69 |
| Enoxaparin 40 mg | Mean Change From Baseline in Diastolic Blood Pressure in Treated Participants During Treatment Period | Day 30 of Treatment + 2 (N=2227,2301) | -0.5 mmHg | Standard Deviation 12.78 |
| Enoxaparin 40 mg | Mean Change From Baseline in Diastolic Blood Pressure in Treated Participants During Treatment Period | Day of Discharge from Hospital (N=1607, 1625) | -0.4 mmHg | Standard Deviation 12.32 |
Secondary
Mean Change From Baseline in Heart Rate in Treated Participants
Heart Rate was obtained during Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days. Heart rate was measured in beats per minute (bpm) and could have been taken with participants either sitting, standing, or supine.
Time frame: Day 1 to last dose of study drug plus 2 days
Population: Participants who received at least one dose of study drug, had a baseline value, and had a value on the day specified were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Apixaban 2.5 mg | Mean Change From Baseline in Heart Rate in Treated Participants | Hospital Discharge (N=1606,1622) | -5.4 bpm | Standard Deviation 14.08 |
| Apixaban 2.5 mg | Mean Change From Baseline in Heart Rate in Treated Participants | Day 30 of treatment (N=2225,2299) | -4.0 bpm | Standard Deviation 15.62 |
| Enoxaparin 40 mg | Mean Change From Baseline in Heart Rate in Treated Participants | Hospital Discharge (N=1606,1622) | -5.1 bpm | Standard Deviation 14.07 |
| Enoxaparin 40 mg | Mean Change From Baseline in Heart Rate in Treated Participants | Day 30 of treatment (N=2225,2299) | -4.3 bpm | Standard Deviation 14.83 |
Secondary
Mean Change From Baseline in Systolic Blood Pressure in Treated Participants During Treatment Period
Systolic blood pressure was obtained during Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days. Blood pressure was measured in millimeters of mercury (mmHg) and could have been taken either sitting, standing, or supine.
Time frame: Day 1 to last dose of study drug plus 2 days
Population: Participants who received at least one dose of study drug, had a baseline value, and had a value on the day specified were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Apixaban 2.5 mg | Mean Change From Baseline in Systolic Blood Pressure in Treated Participants During Treatment Period | Discharge from Hospital (N=1607, 1625) | -3.0 mmHg | Standard Deviation 19.12 |
| Apixaban 2.5 mg | Mean Change From Baseline in Systolic Blood Pressure in Treated Participants During Treatment Period | Day 30 of Treatment + 2 (N=2227, 2301) | -2.3 mmHg | Standard Deviation 19.79 |
| Enoxaparin 40 mg | Mean Change From Baseline in Systolic Blood Pressure in Treated Participants During Treatment Period | Day 30 of Treatment + 2 (N=2227, 2301) | -2.9 mmHg | Standard Deviation 20.61 |
| Enoxaparin 40 mg | Mean Change From Baseline in Systolic Blood Pressure in Treated Participants During Treatment Period | Discharge from Hospital (N=1607, 1625) | -2.4 mmHg | Standard Deviation 19.8 |
Secondary
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Deaths, and Discontinuations Due to AEs During the Treatment Period in Treated Participants
Treatment Period=includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drugs for AEs, and 30 days after last dose of study drugs for SAEs and deaths.
Time frame: Day 1, first dose of study drug, to last dose of study drug plus 2 days (AEs), plus 30 days (SAEs, Deaths)
Population: Participants who received at least one dose of study drug were analyzed (As Treated population).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban 2.5 mg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Deaths, and Discontinuations Due to AEs During the Treatment Period in Treated Participants | SAEs | 611 participants |
| Apixaban 2.5 mg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Deaths, and Discontinuations Due to AEs During the Treatment Period in Treated Participants | Discontinuations Due to AE | 290 participants |
| Apixaban 2.5 mg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Deaths, and Discontinuations Due to AEs During the Treatment Period in Treated Participants | AEs | 1871 participants |
| Apixaban 2.5 mg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Deaths, and Discontinuations Due to AEs During the Treatment Period in Treated Participants | Deaths | 131 participants |
| Apixaban 2.5 mg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Deaths, and Discontinuations Due to AEs During the Treatment Period in Treated Participants | Bleeding AEs | 244 participants |
| Enoxaparin 40 mg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Deaths, and Discontinuations Due to AEs During the Treatment Period in Treated Participants | Deaths | 133 participants |
| Enoxaparin 40 mg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Deaths, and Discontinuations Due to AEs During the Treatment Period in Treated Participants | SAEs | 601 participants |
| Enoxaparin 40 mg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Deaths, and Discontinuations Due to AEs During the Treatment Period in Treated Participants | Bleeding AEs | 221 participants |
| Enoxaparin 40 mg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Deaths, and Discontinuations Due to AEs During the Treatment Period in Treated Participants | Discontinuations Due to AE | 262 participants |
| Enoxaparin 40 mg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Deaths, and Discontinuations Due to AEs During the Treatment Period in Treated Participants | AEs | 1910 participants |
Secondary
Number of Participants With Events of Special Interest for Liver Function and Neurology During Treatment Period in Treated Participants With Available Measurements
Special interest include: liver function test increases, AEs related to liver function, and neurologic AEs. Treatment Period includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drug when summarizing AEs and through 30 days after the last dose when summarizing SAEs.
Time frame: Day 1 to last dose of study drug plus 2 days (AEs) and plus 30 days (SAEs)
Population: Participants who received at least one dose of study drug, and had available laboratory results associated with the event and treatment group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban 2.5 mg | Number of Participants With Events of Special Interest for Liver Function and Neurology During Treatment Period in Treated Participants With Available Measurements | Liver-related AEs | 127 participants |
| Apixaban 2.5 mg | Number of Participants With Events of Special Interest for Liver Function and Neurology During Treatment Period in Treated Participants With Available Measurements | Neurologic AEs | 45 participants |
| Apixaban 2.5 mg | Number of Participants With Events of Special Interest for Liver Function and Neurology During Treatment Period in Treated Participants With Available Measurements | Liver-related SAEs | 9 participants |
| Apixaban 2.5 mg | Number of Participants With Events of Special Interest for Liver Function and Neurology During Treatment Period in Treated Participants With Available Measurements | Neurologic SAEs | 5 participants |
| Enoxaparin 40 mg | Number of Participants With Events of Special Interest for Liver Function and Neurology During Treatment Period in Treated Participants With Available Measurements | Liver-related SAEs | 12 participants |
| Enoxaparin 40 mg | Number of Participants With Events of Special Interest for Liver Function and Neurology During Treatment Period in Treated Participants With Available Measurements | Neurologic SAEs | 1 participants |
| Enoxaparin 40 mg | Number of Participants With Events of Special Interest for Liver Function and Neurology During Treatment Period in Treated Participants With Available Measurements | Liver-related AEs | 142 participants |
| Enoxaparin 40 mg | Number of Participants With Events of Special Interest for Liver Function and Neurology During Treatment Period in Treated Participants With Available Measurements | Neurologic AEs | 42 participants |
Secondary
Number of Participants With Liver-Related Elevations During the Treatment Period in Treated Participants
Liver function tests: Alanine aminotransferase (ALT) U/L; Aspartate aminotransferase (AST) U/L; Alkaline phosphatase U/L; Total Bilirubin (TBili) mg/dL. Elevations consist of \>3\*Upper Limit of Normal (ULN) for ALT and AST and elevation of \>2\*ULN for Bilirubin.
Time frame: Day 1 to last dose of study drug plus 2 days
Population: Participants who received at least one dose of study drug and had available laboratory measurements.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban 2.5 mg | Number of Participants With Liver-Related Elevations During the Treatment Period in Treated Participants | TBili >2*ULN (N= 2853, 2884) | 13 participants |
| Apixaban 2.5 mg | Number of Participants With Liver-Related Elevations During the Treatment Period in Treated Participants | ALT Elevation >3*ULN (N=2827, 2861) | 22 participants |
| Apixaban 2.5 mg | Number of Participants With Liver-Related Elevations During the Treatment Period in Treated Participants | ALT or AST >3*ULN + TBili >2*ULN (N=2818,2855) | 2 participants |
| Apixaban 2.5 mg | Number of Participants With Liver-Related Elevations During the Treatment Period in Treated Participants | AST + ALT >3*ULN on same date (N= 2827, 2861) | 14 participants |
| Apixaban 2.5 mg | Number of Participants With Liver-Related Elevations During the Treatment Period in Treated Participants | ALT>3*ULN + TBili >2*ULN (N=2817, 2853) | 0 participants |
| Apixaban 2.5 mg | Number of Participants With Liver-Related Elevations During the Treatment Period in Treated Participants | AST Elevation >3*ULN (N=2831, 2863) | 23 participants |
| Enoxaparin 40 mg | Number of Participants With Liver-Related Elevations During the Treatment Period in Treated Participants | ALT>3*ULN + TBili >2*ULN (N=2817, 2853) | 2 participants |
| Enoxaparin 40 mg | Number of Participants With Liver-Related Elevations During the Treatment Period in Treated Participants | ALT Elevation >3*ULN (N=2827, 2861) | 32 participants |
| Enoxaparin 40 mg | Number of Participants With Liver-Related Elevations During the Treatment Period in Treated Participants | AST + ALT >3*ULN on same date (N= 2827, 2861) | 13 participants |
| Enoxaparin 40 mg | Number of Participants With Liver-Related Elevations During the Treatment Period in Treated Participants | TBili >2*ULN (N= 2853, 2884) | 14 participants |
| Enoxaparin 40 mg | Number of Participants With Liver-Related Elevations During the Treatment Period in Treated Participants | ALT or AST >3*ULN + TBili >2*ULN (N=2818,2855) | 2 participants |
| Enoxaparin 40 mg | Number of Participants With Liver-Related Elevations During the Treatment Period in Treated Participants | AST Elevation >3*ULN (N=2831, 2863) | 28 participants |
Secondary
Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants
Bicarbonate milliequivalents/Liter (mEq/L) Low/High: \< 0.75\*LLN or \> 1.25\*ULN, or if PreRx \< LLN then use \< 0.75\* PreRx or \> ULN if PreRx \> ULN then use \> 1.25\*PreRx or \< LLN; Serum Calcium mg/dL Low/High: \< 0.8\*LLN or \> 1.2\*ULN, or if PreRx \< LLN then use \< 0.75\*PreRx or \> ULN if PreRx \> ULN then use \> 1.25\*PreRx or \< LLN; Serum Chloride mEq/L: \< 0.9\*LLN or \> 1.1\*ULN, or if PreRx \< LLN then use \< 0.9\*PreRx or \> ULN if PreRx \> ULN then use \> 1.1\*PreRx or \< LLN; Serum Potassium mEq/L: \< 0.9\*LLN or \> 1.1\*ULN, or if PreRx \< LLN then use \< 0.9\*PreRx or \> ULN if PreRx \> ULN then use \> 1.1\*PreRx or \< LLN; Serum Sodium mEq/L: \< 0.95\*LLN or \> 1.05\*ULN, or if PreRx \< LLN then use \< 0.95\*PreRx or \> ULN if PreRx \> ULN then use \> 1.05\*PreRx or \< LLN. Samples obtained at Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days.
Time frame: Day 1 to last dose of study drug plus 2 days
Population: Participants who received at least one dose of study drug, had a pre-therapy value, and had a value on the day specified were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants | Chloride < 0.9*LLN (N=2861, 2886) | 25 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants | Chloride > 1.1*ULN (N=2861, 2886) | 5 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants | Bicarbonate > 1.25*ULN (N=2831, 2855) | 6 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants | Calcium < 0.8*LLN (N=2861, 2893) | 6 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants | Calcium > 1.2*ULN (N=2861, 2893) | 3 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants | Bicarbonate < 0.75*LLN (N=2831, 2855) | 5 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants | Potassium < 0.9*LLN (N=2851, 2878) | 61 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants | Potassium > 1.1*ULN (N=2851, 2878) | 140 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants | Sodium < 0.95*LLN (N=2862, 2888) | 23 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants | Sodium > 1.05*ULN (N=2862, 2888) | 9 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants | Potassium > 1.1*ULN (N=2851, 2878) | 137 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants | Chloride < 0.9*LLN (N=2861, 2886) | 25 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants | Bicarbonate > 1.25*ULN (N=2831, 2855) | 4 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants | Bicarbonate < 0.75*LLN (N=2831, 2855) | 6 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants | Sodium > 1.05*ULN (N=2862, 2888) | 6 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants | Potassium < 0.9*LLN (N=2851, 2878) | 58 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants | Calcium < 0.8*LLN (N=2861, 2893) | 8 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants | Sodium < 0.95*LLN (N=2862, 2888) | 25 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants | Calcium > 1.2*ULN (N=2861, 2893) | 3 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants | Chloride > 1.1*ULN (N=2861, 2886) | 1 participants |
Secondary
Number of Participants With Marked Abnormalities in Glucose, Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests During the Treatment Period in Treated Participants
Creatine kinase High: \>5\*ULN Units/Liter (U/L); Total Protein High/Low: \< 0.9 \*LLN or \> 1.1\*ULN, or if PreRx \< LLN then use 0.9\* PreRx or \> ULN if PreRx \> ULN then use 1.1 \*PreRx or \<LLN; Uric acid High: \> 1.5\* ULN, or if PreRx \> ULN then use \> 2 \*PreRx. Glucose Fasting: \<0.9\*LLN or \> 1.5\*ULN or if PreRx \< LLN then use \< 0.8\*PreRx or \> ULN, if PreRx \> ULN then use \>2.0\*PreRx. Samples obtained at Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) ± 2days.
Time frame: Day 1 to last dose of study drug plus 2 days
Population: Participants who received at least one dose of study drug, had a pre-therapy value, and had a value on the day specified were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Glucose, Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests During the Treatment Period in Treated Participants | Creatine kinase >5*ULN U/L(N=2856, 2888) | 8 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Glucose, Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests During the Treatment Period in Treated Participants | Uric acid > 1.5* ULN (N=2862, 2889) | 47 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Glucose, Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests During the Treatment Period in Treated Participants | Glucose Fasting <0.9*LLN (N=284,287) | 5 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Glucose, Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests During the Treatment Period in Treated Participants | Glucose Fasting > 1.5*ULN (N=284,287) | 39 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Glucose, Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests During the Treatment Period in Treated Participants | Total Protein < 0.9 *LLN (N=2864, 2890) | 78 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Glucose, Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests During the Treatment Period in Treated Participants | Total Protein > 1.1*ULN (N=2864, 2890) | 16 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Glucose, Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests During the Treatment Period in Treated Participants | Total Protein < 0.9 *LLN (N=2864, 2890) | 51 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Glucose, Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests During the Treatment Period in Treated Participants | Creatine kinase >5*ULN U/L(N=2856, 2888) | 10 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Glucose, Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests During the Treatment Period in Treated Participants | Glucose Fasting > 1.5*ULN (N=284,287) | 30 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Glucose, Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests During the Treatment Period in Treated Participants | Uric acid > 1.5* ULN (N=2862, 2889) | 44 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Glucose, Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests During the Treatment Period in Treated Participants | Total Protein > 1.1*ULN (N=2864, 2890) | 8 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Glucose, Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests During the Treatment Period in Treated Participants | Glucose Fasting <0.9*LLN (N=284,287) | 3 participants |
Secondary
Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants
Lower limit of normal (LLN). Upper limit of normal (ULN). Pre-therapy (PreRx). Absolute (Abs) neutrophil count, bands + neutrophils (ANC). Cells per microliter (c/µL). Grams per deciliter (g/dL). Cells per Liter (c/L). Millimeter (MM). Absolute (Abs). Hemoglobin: \>2 g/dL decrease compared to PreRx value or value \<=8 g/dL; Hematocrit: \<0.75\*PreRx; Erythrocytes: \<0.75\*PreRx c/µL; Leukocytes: \<0.75\*LLN or \> 1.25\*ULN, if PreRx \<LLN then use \<0.8\*PreRx or \>ULN, if PreRx \>ULN then use \>1.2\*PreRx or \< LLN; Platelet count: \< 100\*10\^9 c/L; ANC: \< 1.00\*10\^3 c/µL; Abs eosinophils: \> 0.75\*10\^3 c/µL; Abs Basophils: \> 400/MM\^3; Abs Monocytes \> 2000/MM\^3; Abs Lymphocytes: \< 0.750\*10\*3 c/ µL or \> 7.5\*10\^3 c/ µL. Samples were obtained at Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days.
Time frame: Day 1 to last dose of study drug plus 2 days
Population: Participants who received at least one dose of study drug, had a pre-therapy value, and had a value on the day specified were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants | Abs Monocytes > 2000/MM^3 (N= 19, 25) | 1 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants | Erythrocytes <0.75*PreRx c/µL (N=2697, 2730) | 28 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants | Hemoglobin >2 g/dL decrease (N=2835, 2871) | 133 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants | Hematocrit <0.75*PreRx (N=2688, 2722) | 23 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants | Platelet Count < 100*10^9 c/L (N=2761, 2799) | 9 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants | Leukocytes <0.75*LLN (N= 2835, 2869) | 64 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants | Leukocytes > 1.25*ULN (N=2835, 2869) | 331 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants | Abs Eosinophils > 0.75*10^3 c/µL (N=20, 24) | 1 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants | Abs Lymphocytes < 0.750*10*3 c/ µL (N=20, 24) | 4 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants | Abs Eosinophils > 0.75*10^3 c/µL (N=20, 24) | 1 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants | Leukocytes <0.75*LLN (N= 2835, 2869) | 55 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants | Abs Monocytes > 2000/MM^3 (N= 19, 25) | 0 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants | Platelet Count < 100*10^9 c/L (N=2761, 2799) | 7 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants | Hemoglobin >2 g/dL decrease (N=2835, 2871) | 98 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants | Leukocytes > 1.25*ULN (N=2835, 2869) | 283 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants | Hematocrit <0.75*PreRx (N=2688, 2722) | 17 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants | Abs Lymphocytes < 0.750*10*3 c/ µL (N=20, 24) | 2 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants | Erythrocytes <0.75*PreRx c/µL (N=2697, 2730) | 16 participants |
Secondary
Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants
Blood urea nitrogen (BUN), milligrams/deciliter (mg/dL), units per liter (U/L). BUN mg/dL \> 1.5\*ULN; Creatinine mg/dL: \> 1.5\*ULN; Alanine aminotransferase (ALT) U/L: \> 3\*ULN; Aspartate aminotransferase (AST) U/L: \> 3\*ULN; Alkaline phosphatase U/L: \> 2\*ULN; Bilirubin Direct mg/dL: \> 1.5\*ULN; Bilirubin Total mg/dL: \> 2\*ULN. Samples for laboratories obtained at Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days.
Time frame: Day 1 to last dose of study drug plus 2 days
Population: Participants who received at least one dose of study drug, had a pre-therapy value, and had a value on the day specified were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants | AST U/L > 3*ULN (N=2831, 2863) | 24 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants | Bilirubin Total mg/dL > 2*ULN (N=2853, 2884) | 17 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants | Alkaline phosphatase U/L > 2*ULN(N=2866, 2895) | 35 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants | BUN mg/dL > 1.5*ULN (N=2864, 2891) | 194 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants | Bilirubin Direct mg/dL > 1.5*ULN (N=2782, 2821) | 123 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants | Creatinine mg/dL > 1.5*ULN (N=2862, 2892) | 150 participants |
| Apixaban 2.5 mg | Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants | ALT U/L > 3*ULN (N=2827, 2861) | 23 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants | Creatinine mg/dL > 1.5*ULN (N=2862, 2892) | 156 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants | ALT U/L > 3*ULN (N=2827, 2861) | 33 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants | Alkaline phosphatase U/L > 2*ULN(N=2866, 2895) | 47 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants | AST U/L > 3*ULN (N=2831, 2863) | 29 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants | Bilirubin Direct mg/dL > 1.5*ULN (N=2782, 2821) | 106 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants | Bilirubin Total mg/dL > 2*ULN (N=2853, 2884) | 15 participants |
| Enoxaparin 40 mg | Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants | BUN mg/dL > 1.5*ULN (N=2864, 2891) | 188 participants |
Secondary
Symptomatic Adjudicated VTE or VTE-Related Death With Onset During the Intended Treatment Period
Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE: nonfatal PE, symptomatic DVT, or asymptomatic proximal DVT detected by ultrasound. VTE-related death: fatal PE or sudden death for which VTE cannot be excluded as a cause. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Population: Randomized participants except those with an inadequate assessment for symptomatic events that are part of the endpoint during the intended treatment were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Symptomatic Adjudicated VTE or VTE-Related Death With Onset During the Intended Treatment Period | 0.40 Event Rate (%) |
| Enoxaparin 40 mg | Symptomatic Adjudicated VTE or VTE-Related Death With Onset During the Intended Treatment Period | 0.80 Event Rate (%) |
95% CI: [0.26, 0.96]
95% CI: [-0.78, -0.03]