Venous Thrombosis
Conditions
Brief summary
The purpose of this study is to evaluate the effects of an investigational blood thinner, apixaban, in preventing venous thromboembolic (VTE) recurrence or death in patients with deep vein thrombosis (DVT) or pulmonary embolism (PE)
Interventions
DRUGEnoxaparin
solution, subcutaneous, 1 mg/kg Q12h until International normalized ratio (INR) ≥2.
DRUGwarfarin
tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months
DRUGPlacebo for apixaban
tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months
DRUGPlacebo for enoxaparin
solution, subcutaneous, 1 mg/kg Q12h until sham INR ≥2.
DRUGPlacebo for warfarin
tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months
DRUGapixaban
tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months
Sponsors
Pfizer
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and women ≥ 18 years of age * Clinical diagnosis of DVT or PE
Exclusion criteria
* Contraindications for enoxaparin or warfarin * Active bleeding or high risk for serious bleeding * Short life expectancy * Uncontrolled high blood pressure * Significantly impaired kidney or liver function
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or VTE-Related Death During 6 Months of Treatment | Day 1 to Week 24 + 2 Days or 355 days (Discontinued Early) | VTE: nonfatal deep vein thrombosis (DVT) or nonfatal pulmonary embolism (PE). All events were adjudicated by an ICAC blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants): n/N (n=number of participants with observation; N=total number of efficacy evaluable participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint: events at any time from randomization until end of intended treatment, regardless whether drug treatment was received. All randomized participants with a non-missing primary endpoint were summarized. Missing endpoint = outcomes which could not be documented on or after study Day 154. Participants were categorized to the assigned group regardless of the treatment actually received (intent-to-treat). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adjudicated Symptomatic Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period | Day 1 to Week 24 + + 2 Days or 355 Days (Discontinued Early) | PE adjudicated by an ICAC blinded to treatment. PE: spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Includes events that occurred during the intended treatment period, regardless of whether the participant received study medication (ITT principle). Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants, excluding those with missing endpoint). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). |
| Incidence of Adjudicated Composite of Recurrent Symptomatic VTE or Cardiovascular (CV)-Related Death | Day 1 up to 24 Weeks + 2 Days or 355 Days (Discontinued Early) | VTE included: nonfatal DVT or nonfatal PE. All events were adjudicated by an ICAC blinded to treatment. DVT was assessed by compression ultrasound and/or venography; PE was assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of participants with observation; N=total number of efficacy evaluable participants, participants with missing endpoint information excluded). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received, ie, ITT principle. Each participant scored as having an event only if the participant experienced one or more of the elements of the composite. |
| Incidence of Adjudicated Composite of Recurrent Symptomatic VTE or VTE-related Death or Major Bleeding | Day 1 up to 24 Weeks + 2 Days or 355 Days (Discontinued Early) | VTE included: nonfatal DVT or nonfatal PE. All events were adjudicated by an ICAC blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Major bleeding defined by International Society on Thrombosis and Haemostasis: acute, clinically overt bleeding associated with decrease in hemoglobin (Hgb) of 2 g/dL or more or bleeding leading to transfusion or bleeding in a critical site or bleeding that is fatal . Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants, excluding those with missing endpoint and including those not in the efficacy evaluable population with a bleeding event that occurred during treatment period. Events included regardless of whether or not participant received treatment, ie, ITT principle |
| Incidence of Adjudicated Composite of Recurrent Symptomatic VTE, Myocardial Infarction, Stroke, CV-related Death, Clinically Relevant Non-major (CRNM) Bleeding or Major Bleeding | Day 1 up to 24 Weeks + 2 Days or 355 Days (Discontinued Early) | VTE=Nonfatal DVT or nonfatal PE adjudicated by ICAC blinded to treatment. DVT: compression ultrasound and/or venography; PE: spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Major Bleeding = acute, clinically overt bleeding: decrease in Hgb of 2 g/dL or more or bleeding leading to transfusion or bleeding in a critical site or fatal bleeding. CRNM = acute clinically overt bleeding: compromising hemodynamics, leading to hospitalization, hematoma, epistasis \>5 minutes or repetitive, gingival bleeding, hematuria, macroscopic gastrointestinal hemorrhage, rectal blood loss, hemoptysis. n/N (n=number of participants with observation; N=Total number of participants, excluding those with missing endpoint and including those not in the efficacy evaluable population with a bleeding event that occurred during treatment period). Events included regardless of whether or not treatment was received (ITT). |
| Incidence of Adjudicated Symptomatic Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period | Day 1 up to 24 Weeks + 2 Days or 355 Days (Discontinued Early) | DVT adjudicated by an ICAC blinded to treatment. DVT evaluated by: compression ultrasound and/or venography. Includes events that occurred during the intended treatment period, regardless of whether the participant received study medication, intent to treat principle (ITT). Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants, excluding those with missing endpoint). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). |
| Incidence of Adjudicated Venous Thromboembolism (VTE)-Related Death During the Intended Treatment Period | Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early) | VTE-related death included: DVT-related death or PE-related death. All events were adjudicated by an ICAC blinded to treatment. DVT was assessed by compression ultrasound and/or venography; PE was assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of participants with observation; N=total number of participants in respective treatment groups excluding participants with missing endpoint information). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Includes events that occur during the intended treatment period regardless of whether or not the participant received study medication (ITT principle). |
| Incidence of Cardiovascular (CV)-Related Death Including VTE-related Death During the Intended Treatment Period | Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early) | VTE-related death included: DVT-related death or PE-related death. All events were adjudicated by an ICAC blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of participants with observation; N=total number of participants in respective treatment groups excluding participants with missing endpoint information). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Includes events that occur during the intended treatment period regardless of whether or not the participant received study medication (ITT principle). |
| Incidence of All-Cause Death During the Intended Treatment Period | Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early) | Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Includes events that occurred during the intended treatment period, regardless of whether the participant received study medication (ITT principle). Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants, excluding those with missing endpoint information). |
| Incidence of Adjudicated Major Bleeding During the Treatment Period in Treated Participants | Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early) | All events were adjudicated by an ICAC blinded to treatment. Bleeding defined by International Society on Thrombosis and Haemostasis: Major Bleeding: acute, clinically overt bleeding: decrease in hemoglobin (hgb) of 2 g/dL or more or bleeding leading to transfusion or bleeding in a critical site or fatal bleeding. Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants in respective treatment group (all participants who received at least one dose of study drug). Participants were categorized to the treatment group to which they were assigned unless incorrect study treatment was received throughout the study, in which case the participant was categorized according to the treatment received. |
| Incidence of Adjudicated Composite of Recurrent Symptomatic Venous Thromboembolism (VTE) or All-Cause Death | Day 1 up to 24 Weeks + 2 Days or 355 Days (Discontinued Early) | VTE included: nonfatal DVT or nonfatal PE. All events were adjudicated by an ICAC blinded to treatment. DVT was assessed by compression ultrasound and/or venography; PE was assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of participants with observation; N=total number of efficacy evaluable participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received, ie intent to treat (ITT) principle. Each participant scored as having an event only if they experienced one or more of the elements of the composite. Participants with missing endpoint information excluded. |
| Incidence of Adjudicated Clinically Relevant Non Major (CRNM) Bleeding During the Treatment Period in Treated Participants | Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early) | Bleeding defined by International Society on Thrombosis and Haemostasis: CRNM defined as acute clinically overt bleeding: compromising hemodynamics, leading to hospitalization, hematoma, epistasis \>5 minutes or repetitive, gingival bleeding, hematuria, macroscopic gastrointestinal hemorrhage, rectal blood loss, hemoptysis. All events were adjudicated by an ICAC blinded to treatment. Event rate (proportion of participants with event): calculated as n/N (n=number of participants with observation; N=Total number of participants in respective treatment group (all participants who received at least one dose of study drug). Participants were categorized to the treatment group to which they were assigned unless incorrect study treatment was received throughout the study, in which case the participant was categorized according to the treatment received. |
| Incidence of Adjudicated Minor Bleeding During the Treatment Period in Treated Participants | Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early) | Bleeding defined by International Society on Thrombosis and Haemostasis: Minor bleeding: all acute clinically overt bleeding events not meeting the criteria for either major bleeding or CRNM. All events wre adjudicated by an ICAC blinded to treatment. Event rate (proportion of participants) calculated as n/N (n=number of participants with observation; N=Total number of participants in respective treatment group (all participants who received at least one dose of study drug). Participants were categorized to the treatment group to which they were assigned unless incorrect study treatment was received throughout the study, in which case the participant was categorized according to the treatment received. |
| Incidence of Adjudicated Total Bleeding During the Treatment Period in Treated Participants | Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early) | Bleeding defined by International Society on Thrombosis and Haemostasis: Total Bleeding defined as any of major, CRNM, or minor bleeding. All events were adjudicated by an ICAC blinded to treatment. Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants in respective treatment group (all participants who received at least one dose of study drug). Participants were categorized to the treatment group to which they were assigned unless incorrect study treatment was received throughout the study, in which case the participant was categorized according to the treatment received. |
| Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Discontinuations Due to AEs and Death During the Treatment Period in Treated Participants | First dose to last dose of 24 Weeks + 2 days (AEs) or + 30 days (SAEs) or until drug discontinued | Treated Participants: all who received at least 1 dose of study drug. Participants categorized to the treatment group to which they were assigned unless incorrect study treatment was received throughout the study, in which case the participant was categorized according to treatment received. Included all SAEs and AEs with onset from first dose to last dose + 2 days (for AEs) or + 30 days (for SAEs); note; bleeding AEs and SAEs from first dose to last dose + 2 days included. Discontinuations due to AE included all AEs/SAEs from first dose until drug was discontinued. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. |
| Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early) | 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). White blood cells: \< 0.75\*LLN, \> 1.25\*ULN; Hemoglobin: \<= 11.5 g/dL (males), \<= 9.5 g/dL (females); Hematocrit: \<= 37% (males), \<= 32% (females); Erythrocytes: \<0.75\*10\^6 c/µL\*PreRx; Platelet count: \< 75\*10\^9 c/L, \> 700\*10\^9 c/L; ANC: \< 1.00\*10\^3 c/µL; Abs eosinophils: \> 0.750\*10\^3 c/µL; Abs Basophils: \> 400/MM\^3; Abs Monocytes\> 2000/MM\^3; Abs Lymphocytes: \< 0.750\*10\*3 c/ µL, \> 7.5\*10\^3 c/ µL. |
| Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests | Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early) | Bicarbonate milliequivalents/Liter (mEq/L) Low/High: \< 0.75\*LLN or \> 1.25\*ULN, or if pre-dose \< LLN then use \< 0.75\*pre-dose or \> ULN if pre-dose \> ULN then use \> 1.25\*pre-dose or \< LLN; Serum Calcium mg/dL Low/High: \< 0.8\*LLN or \> 1.2\*ULN, or if pre-dose \< LLN then use \< 0.75\*pre-dose or \> ULN if pre-dose \> ULN then use \> 1.25\*pre-dose or \< LLN; Serum Chloride mEq/L: \< 0.9\*LLN or \> 1.1\*ULN, or if pre-dose \< LLN then use \< 0.9\*pre-dose or \> ULN if pre-dose \> ULN then use \> 1.1\*pre-dose or \< LLN; Serum Potassium mEq/L: \< 0.9\*LLN or \> 1.1\*ULN, or if pre-dose \< LLN then use \< 0.9\*pre-dose or \> ULN if pre-dose \> ULN then use \> 1.1\*pre-dose or \< LLN; Serum Sodium mEq/L: \< 0.95\*LLN or \> 1.05\*ULN, or if pre-dose \< LLN then use \< 0.95\*pre-dose or \> ULN if pre-dose \> ULN then use \> 1.05\*pre-dose or \< LLN. |
| Number of Treated Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests | Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early) | Blood urea nitrogen (BUN), milligrams/deciliter (mg/dL), units per liter (U/L). BUN mg/dL High: \> 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. |
| Number of Treated Participants With Marked Abnormalities in Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests | Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early) | Creatine kinase High: \>5\*ULN Units/Liter (U/L); Total Protein High/Low: \< 0.9 \*LLN or \> 1.1\*ULN, or if pre-dose \< LLN then use 0.9\* pre-dose or \> ULN if pre-dose \> ULN then use 1.1 \*pre-dose or \<LLN; Uric acid High: \> 1.5\* ULN, or if pre-dose \> ULN then use \> 2 \*pre-dose. |
| Number of Treated Participants With Marked Abnormalities in Urinalysis Laboratory Tests | Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early) | All tests in urine: Glucose: If missing pre-dose use ≥ 2, or if value ≥ 4, or if pre-dose = 0 or 0.5 use ≥ 2, or if pre-dose = 1 use ≥ 3, or if pre-dose = 2 or 3 use ≥ 4; Protein: If missing pre-dose use ≥ 2, or if value ≥ 4, or if pre-dose = 0 or 0.5 use ≥ 2, or if pre-dose = 1 use ≥ 3, or if pre-dose = 2 or 3 use ≥ 4; Blood: If missing pre-dose use ≥ 2, or if value ≥ 4, or if pre-dose = 0 or 0.5 use ≥ 2, or if pre-dose = 1 use ≥ 3, or if pre-dose = 2 or 3 use ≥ 4; Leukocyte esterase: If missing pre-dose use ≥ 2, or if value ≥ 4, or if pre-dose = 0 or 0.5 use ≥ 2, or if pre-dose = 1 use ≥ 3, or if pre-dose = 2 or 3 use ≥ 4;Red blood cells (RBC): If missing pre-dose use ≥ 2, or if value ≥ 4, or if pre-dose = 0 or 0.5 use ≥ 2, or if pre-dose = 1 use ≥ 3, or if pre-dose = 2 or 3 use ≥ 4; White blood cells (WBC): If missing pre-dose use ≥ 2, or if value ≥ 4, or if pre-dose = 0 or 0.5 use ≥ 2, or if pre-dose = 1 use ≥ 3, or if pre-dose = 2 or 3 use ≥ 4. |
| Incidence of Adjudicated Major/CRNM Bleeding During the Treatment Period in Treated Participants | Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early) | Major Bleeding = acute, clinically overt bleeding: decrease in hemoglobin of 2 g/dL or more, or bleeding leading to transfusion, or bleeding in a critical site, or fatal bleeding. CRNM = acute clinically overt bleeding: compromising hemodynamics, leading to hospitalization, hematoma, epistasis \>5 minutes or repetitive, gingival bleeding, hematuria, macroscopic gastrointestinal hemorrhage, rectal blood loss, hemoptysis. Minor =: All acute clinically overt bleeding events not meeting the criteria for either major bleeding or CRNM. All events were adjudicated by an ICAC blinded to treatment. Total bleeding = any of major, or CRNM, or minor bleeding. Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of treated (received at least 1 dose of study drug). |
Countries
Argentina, Australia, Austria, Brazil, Canada, Chile, China, Czechia, Denmark, France, Germany, Hong Kong, Hungary, India, Israel, Italy, Malaysia, Mexico, Norway, Poland, Portugal, Puerto Rico, Romania, Russia, Singapore, South Africa, South Korea, Spain, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
First participant, first visit: 27 August 2008; Last participant, last visit: 12 March 2013.
Pre-assignment details
5614 enrolled, 5395 randomized; Reasons for non-randomization: 173 did not meet inclusion/exclusion criteria; 12 withdrew consent; 5 had clinical reason to continue current treatment; 3 administrative reason by sponsor; 1 death; 1 adverse event (AE); 24 other reasons. 1 site (5 patients) excluded from analysis due to unconfirmed accuracy of data.
Participants by arm
| Arm | Count |
|---|---|
| Apixaban apixaban: tablets, oral, 10 milligram (mg) tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months.
Placebo for enoxaparin: solution, subcutaneous, 1milligram per kilogram (mg/kg) every 12 hours until sham International normalized ratio (INR) greater than, equal to ( ≥) 2.
Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months | 2,691 |
| Enoxaparin + Warfarin Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2.
warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months
Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months | 2,704 |
| Total | 5,395 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Completed Study Follow Up | Death | 28 | 34 |
| Completed Study Follow Up | Lost to Follow-up | 18 | 16 |
| Completed Study Follow Up | non-specified | 1 | 0 |
| Completed Study Follow Up | Withdrawal by Subject | 23 | 29 |
| Randomized, Completed 6 Months of Study | Administrative reason | 1 | 1 |
| Randomized, Completed 6 Months of Study | Adverse Event | 150 | 182 |
| Randomized, Completed 6 Months of Study | Death | 20 | 26 |
| Randomized, Completed 6 Months of Study | Fails to meet inclusion/exclusion | 13 | 9 |
| Randomized, Completed 6 Months of Study | Lost to Follow-up | 14 | 14 |
| Randomized, Completed 6 Months of Study | Other | 107 | 107 |
| Randomized, Completed 6 Months of Study | Poor or non-compliance | 20 | 23 |
| Randomized, Completed 6 Months of Study | Pregnancy | 3 | 2 |
| Randomized, Completed 6 Months of Study | Withdrawal by Subject | 49 | 49 |
Baseline characteristics
| Characteristic | Apixaban | Enoxaparin + Warfarin | Total |
|---|---|---|---|
| Age, Continuous | 57.2 years STANDARD_DEVIATION 15.98 | 56.7 years STANDARD_DEVIATION 16.01 | 56.9 years STANDARD_DEVIATION 16 |
| Age, Customized 65 to < 75 | 560 participants | 570 participants | 1130 participants |
| Age, Customized Greater than, equal to (>=) 75 | 402 participants | 372 participants | 774 participants |
| Age, Customized Less than (<) 65 | 1729 participants | 1762 participants | 3491 participants |
| Index Event Classification Adjudicated PE | 930 participants | 906 participants | 1836 participants |
| Index Event Classification Adjudicated Proximal DVT | 1749 participants | 1783 participants | 3532 participants |
| Index Event Classification PE | 913 participants | 890 participants | 1803 participants |
| Index Event Classification Proximal DVT | 1778 participants | 1814 participants | 3592 participants |
| Qualifying index Venous Thromboembolic Embolism Not Reported | 3 participants | 3 participants | 6 participants |
| Qualifying index Venous Thromboembolic Embolism Provoked Index VTE | 272 participants | 272 participants | 544 participants |
| Qualifying index Venous Thromboembolic Embolism Unprovoked Index VTE | 2416 participants | 2429 participants | 4845 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 6 participants | 2 participants | 8 participants |
| Race/Ethnicity, Customized Asian | 227 participants | 226 participants | 453 participants |
| Race/Ethnicity, Customized Black or African American | 106 participants | 98 participants | 204 participants |
| Race/Ethnicity, Customized Ethnicity Not Reported | 2304 participants | 2306 participants | 4610 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 20 participants | 18 participants | 38 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 367 participants | 380 participants | 747 participants |
| Race/Ethnicity, Customized Other Race | 89 participants | 85 participants | 174 participants |
| Race/Ethnicity, Customized Race Not Reported | 45 participants | 50 participants | 95 participants |
| Race/Ethnicity, Customized White | 2218 participants | 2243 participants | 4461 participants |
| Region of Enrollment Argentina | 17 participants | 16 participants | 33 participants |
| Region of Enrollment Australia | 56 participants | 64 participants | 120 participants |
| Region of Enrollment Austria | 40 participants | 39 participants | 79 participants |
| Region of Enrollment Brazil | 77 participants | 81 participants | 158 participants |
| Region of Enrollment Canada | 147 participants | 152 participants | 299 participants |
| Region of Enrollment China | 113 participants | 114 participants | 227 participants |
| Region of Enrollment Czech Republic | 140 participants | 134 participants | 274 participants |
| Region of Enrollment Denmark | 69 participants | 72 participants | 141 participants |
| Region of Enrollment France | 140 participants | 149 participants | 289 participants |
| Region of Enrollment Germany | 202 participants | 205 participants | 407 participants |
| Region of Enrollment Hong Kong | 2 participants | 1 participants | 3 participants |
| Region of Enrollment Hungary | 145 participants | 128 participants | 273 participants |
| Region of Enrollment India | 101 participants | 99 participants | 200 participants |
| Region of Enrollment Israel | 162 participants | 163 participants | 325 participants |
| Region of Enrollment Italy | 167 participants | 169 participants | 336 participants |
| Region of Enrollment Korea, Republic of | 2 participants | 2 participants | 4 participants |
| Region of Enrollment Malaysia | 0 participants | 2 participants | 2 participants |
| Region of Enrollment Mexico | 59 participants | 57 participants | 116 participants |
| Region of Enrollment Norway | 40 participants | 32 participants | 72 participants |
| Region of Enrollment Poland | 60 participants | 59 participants | 119 participants |
| Region of Enrollment Portugal | 10 participants | 9 participants | 19 participants |
| Region of Enrollment Romania | 33 participants | 41 participants | 74 participants |
| Region of Enrollment Russian Federation | 178 participants | 174 participants | 352 participants |
| Region of Enrollment Singapore | 5 participants | 5 participants | 10 participants |
| Region of Enrollment South Africa | 70 participants | 77 participants | 147 participants |
| Region of Enrollment Spain | 56 participants | 51 participants | 107 participants |
| Region of Enrollment Ukraine | 213 participants | 211 participants | 424 participants |
| Region of Enrollment United States | 387 participants | 398 participants | 785 participants |
| Sex: Female, Male Female | 1122 Participants | 1106 Participants | 2228 Participants |
| Sex: Female, Male Male | 1569 Participants | 1598 Participants | 3167 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1,014 / 2,676 | 1,207 / 2,689 |
| serious Total, serious adverse events | 417 / 2,676 | 410 / 2,689 |
Outcome results
Primary
Incidence of Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or VTE-Related Death During 6 Months of Treatment
VTE: nonfatal deep vein thrombosis (DVT) or nonfatal pulmonary embolism (PE). All events were adjudicated by an ICAC blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants): n/N (n=number of participants with observation; N=total number of efficacy evaluable participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint: events at any time from randomization until end of intended treatment, regardless whether drug treatment was received. All randomized participants with a non-missing primary endpoint were summarized. Missing endpoint = outcomes which could not be documented on or after study Day 154. Participants were categorized to the assigned group regardless of the treatment actually received (intent-to-treat).
Time frame: Day 1 to Week 24 + 2 Days or 355 days (Discontinued Early)
Population: All randomized participants with a non-missing primary endpoint (n/N: 59/2609; 71/2635, in apixaban, enoxaparin/warfarin, respectively). Intent-to-treat population. Confidence interval (CI) for event rate calculated based on the Wald asymptotic confidence limits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban | Incidence of Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or VTE-Related Death During 6 Months of Treatment | 0.0226 proportion of participants |
| Enoxaparin + Warfarin | Incidence of Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or VTE-Related Death During 6 Months of Treatment | 0.0269 proportion of participants |
Comparison: Hypothesis that apixaban was non-inferior to enoxaparin/warfarin therapy in preventing the recurrence of VTE (nonfatal DVT or nonfatal PE)/VTE-related death.p-value: <0.000195% CI: [0.5965, 1.1802]Yanagawa-Tango-Hiejima
Comparison: Hypothesis that apixaban was non-inferior to enoxaparin/warfarin therapy in preventing the recurrence of VTE (nonfatal DVT or nonfatalPE)/VTE-related death as measured by risk difference.p-value: <0.000195% CI: [-0.0128, 0.004]Yanagawa-Tango-Hiejima
Comparison: Hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint. Inferential testing required demonstration of non-inferiority using both RR and RD plus demonstration of superiority for major bleeding.p-value: 0.312895% CI: [0.5965, 1.1802]Cochran-Mantel-Haenszel
Secondary
Incidence of Adjudicated Clinically Relevant Non Major (CRNM) Bleeding During the Treatment Period in Treated Participants
Bleeding defined by International Society on Thrombosis and Haemostasis: CRNM defined as acute clinically overt bleeding: compromising hemodynamics, leading to hospitalization, hematoma, epistasis \>5 minutes or repetitive, gingival bleeding, hematuria, macroscopic gastrointestinal hemorrhage, rectal blood loss, hemoptysis. All events were adjudicated by an ICAC blinded to treatment. Event rate (proportion of participants with event): calculated as n/N (n=number of participants with observation; N=Total number of participants in respective treatment group (all participants who received at least one dose of study drug). Participants were categorized to the treatment group to which they were assigned unless incorrect study treatment was received throughout the study, in which case the participant was categorized according to the treatment received.
Time frame: Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Population: Total number of participants receiving at least one dose of study drug n/N: 103/2676; 215/2689, in apixaban and enoxaparin/warfarin groups, respectively. CI for event rate calculated based on Wald asymptotic confidence limits. Participants were categorized according to the actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban | Incidence of Adjudicated Clinically Relevant Non Major (CRNM) Bleeding During the Treatment Period in Treated Participants | 0.0385 proportion of participants |
| Enoxaparin + Warfarin | Incidence of Adjudicated Clinically Relevant Non Major (CRNM) Bleeding During the Treatment Period in Treated Participants | 0.0800 proportion of participants |
Comparison: Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.p-value: <0.000195% CI: [0.3815, 0.6022]Cochran-Mantel-Haenszel
Secondary
Incidence of Adjudicated Composite of Recurrent Symptomatic Venous Thromboembolism (VTE) or All-Cause Death
VTE included: nonfatal DVT or nonfatal PE. All events were adjudicated by an ICAC blinded to treatment. DVT was assessed by compression ultrasound and/or venography; PE was assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of participants with observation; N=total number of efficacy evaluable participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received, ie intent to treat (ITT) principle. Each participant scored as having an event only if they experienced one or more of the elements of the composite. Participants with missing endpoint information excluded.
Time frame: Day 1 up to 24 Weeks + 2 Days or 355 Days (Discontinued Early)
Population: All randomized participants with non-missing secondary endpoint (n/N: 84/2609; 104/2635, in apixaban, enoxaparin/warfarin arms, respectively). Participants categorized to assigned arm, regardless of treatment actually received. Intent to Treat principle. Confidence interval (CI) for event rate calculated based on Wald asymptotic confidence limits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban | Incidence of Adjudicated Composite of Recurrent Symptomatic Venous Thromboembolism (VTE) or All-Cause Death | 0.0322 proportion of participants |
| Enoxaparin + Warfarin | Incidence of Adjudicated Composite of Recurrent Symptomatic Venous Thromboembolism (VTE) or All-Cause Death | 0.0395 proportion of participants |
Comparison: Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.p-value: 0.155495% CI: [0.6146, 1.0812]Cochran-Mantel-Haenszel
Secondary
Incidence of Adjudicated Composite of Recurrent Symptomatic VTE, Myocardial Infarction, Stroke, CV-related Death, Clinically Relevant Non-major (CRNM) Bleeding or Major Bleeding
VTE=Nonfatal DVT or nonfatal PE adjudicated by ICAC blinded to treatment. DVT: compression ultrasound and/or venography; PE: spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Major Bleeding = acute, clinically overt bleeding: decrease in Hgb of 2 g/dL or more or bleeding leading to transfusion or bleeding in a critical site or fatal bleeding. CRNM = acute clinically overt bleeding: compromising hemodynamics, leading to hospitalization, hematoma, epistasis \>5 minutes or repetitive, gingival bleeding, hematuria, macroscopic gastrointestinal hemorrhage, rectal blood loss, hemoptysis. n/N (n=number of participants with observation; N=Total number of participants, excluding those with missing endpoint and including those not in the efficacy evaluable population with a bleeding event that occurred during treatment period). Events included regardless of whether or not treatment was received (ITT).
Time frame: Day 1 up to 24 Weeks + 2 Days or 355 Days (Discontinued Early)
Population: Total number participants in each treatment group, excluded those with missing endpoint and included those not in the efficacy evaluable population with bleeding event which occurred during treatment (n/N: 183/2617; 333/2641). Events included as per ITT principle. CI for event rate calculated based on Wald asymptotic confidence limits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban | Incidence of Adjudicated Composite of Recurrent Symptomatic VTE, Myocardial Infarction, Stroke, CV-related Death, Clinically Relevant Non-major (CRNM) Bleeding or Major Bleeding | 0.0699 proportion of participants |
| Enoxaparin + Warfarin | Incidence of Adjudicated Composite of Recurrent Symptomatic VTE, Myocardial Infarction, Stroke, CV-related Death, Clinically Relevant Non-major (CRNM) Bleeding or Major Bleeding | 0.1261 proportion of participants |
Comparison: Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.p-value: <0.000195% CI: [0.4658, 0.6569]Cochran-Mantel-Haenszel
Secondary
Incidence of Adjudicated Composite of Recurrent Symptomatic VTE or Cardiovascular (CV)-Related Death
VTE included: nonfatal DVT or nonfatal PE. All events were adjudicated by an ICAC blinded to treatment. DVT was assessed by compression ultrasound and/or venography; PE was assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of participants with observation; N=total number of efficacy evaluable participants, participants with missing endpoint information excluded). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received, ie, ITT principle. Each participant scored as having an event only if the participant experienced one or more of the elements of the composite.
Time frame: Day 1 up to 24 Weeks + 2 Days or 355 Days (Discontinued Early)
Population: All randomized participants with non-missing secondary endpoint (n/N: 61/2609; 77/2635, in apixaban, enoxaparin/warfarin arms, respectively). Participants categorized to assigned arm, regardless of treatment actually received. Intent to Treat principle. CI for event rate calculated based on Wald asymptotic confidence limits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban | Incidence of Adjudicated Composite of Recurrent Symptomatic VTE or Cardiovascular (CV)-Related Death | 0.0234 proportion of participants |
| Enoxaparin + Warfarin | Incidence of Adjudicated Composite of Recurrent Symptomatic VTE or Cardiovascular (CV)-Related Death | 0.0292 proportion of participants |
Comparison: Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.p-value: 0.184895% CI: [0.5737, 1.1137]Cochran-Mantel-Haenszel
Secondary
Incidence of Adjudicated Composite of Recurrent Symptomatic VTE or VTE-related Death or Major Bleeding
VTE included: nonfatal DVT or nonfatal PE. All events were adjudicated by an ICAC blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Major bleeding defined by International Society on Thrombosis and Haemostasis: acute, clinically overt bleeding associated with decrease in hemoglobin (Hgb) of 2 g/dL or more or bleeding leading to transfusion or bleeding in a critical site or bleeding that is fatal . Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants, excluding those with missing endpoint and including those not in the efficacy evaluable population with a bleeding event that occurred during treatment period. Events included regardless of whether or not participant received treatment, ie, ITT principle
Time frame: Day 1 up to 24 Weeks + 2 Days or 355 Days (Discontinued Early)
Population: Total number of participants in each randomized arm, excluded those with missing endpoint and included those not in the efficacy evaluable population with bleeding event which occurred during treatment (n/N: 73/2610; 118/2635). Confidence interval (CI) for event rate calculated based on Wald asymptotic confidence limits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban | Incidence of Adjudicated Composite of Recurrent Symptomatic VTE or VTE-related Death or Major Bleeding | 0.0280 proportion of participants |
| Enoxaparin + Warfarin | Incidence of Adjudicated Composite of Recurrent Symptomatic VTE or VTE-related Death or Major Bleeding | 0.0448 proportion of participants |
Comparison: Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.p-value: 0.001195% CI: [0.4682, 0.8306]Cochran-Mantel-Haenszel
Secondary
Incidence of Adjudicated Major Bleeding During the Treatment Period in Treated Participants
All events were adjudicated by an ICAC blinded to treatment. Bleeding defined by International Society on Thrombosis and Haemostasis: Major Bleeding: acute, clinically overt bleeding: decrease in hemoglobin (hgb) of 2 g/dL or more or bleeding leading to transfusion or bleeding in a critical site or fatal bleeding. Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants in respective treatment group (all participants who received at least one dose of study drug). Participants were categorized to the treatment group to which they were assigned unless incorrect study treatment was received throughout the study, in which case the participant was categorized according to the treatment received.
Time frame: Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Population: Total number of participants receiving at least one dose of study drug n/N: 15/2676; 49/2689, in apixaban and enoxaparin/warfarin groups, respectively. CI for event rate calculated based on Wald asymptotic confidence limits. Participants were categorized according to the actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban | Incidence of Adjudicated Major Bleeding During the Treatment Period in Treated Participants | 0.0056 proportion of participants |
| Enoxaparin + Warfarin | Incidence of Adjudicated Major Bleeding During the Treatment Period in Treated Participants | 0.0182 proportion of participants |
Comparison: Hypothesis: apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint. As per the hierarchical statistical testing cascade, inferential testing for adjudicated major bleeding occurred because non-inferiority for VTE/VTE-related death (Primary efficacy endpoint) was demonstrated earlier. Rejection of the null hypothesis for equivalence for major bleeding allowed inferential testing for superiority of VTE/VTE-related death.p-value: <0.000195% CI: [0.1728, 0.5452]Cochran-Mantel-Haenszel
Secondary
Incidence of Adjudicated Major/CRNM Bleeding During the Treatment Period in Treated Participants
Major Bleeding = acute, clinically overt bleeding: decrease in hemoglobin of 2 g/dL or more, or bleeding leading to transfusion, or bleeding in a critical site, or fatal bleeding. CRNM = acute clinically overt bleeding: compromising hemodynamics, leading to hospitalization, hematoma, epistasis \>5 minutes or repetitive, gingival bleeding, hematuria, macroscopic gastrointestinal hemorrhage, rectal blood loss, hemoptysis. Minor =: All acute clinically overt bleeding events not meeting the criteria for either major bleeding or CRNM. All events were adjudicated by an ICAC blinded to treatment. Total bleeding = any of major, or CRNM, or minor bleeding. Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of treated (received at least 1 dose of study drug).
Time frame: Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Population: Total number of participants receiving at least one dose of study drug n/N: 115/2676; 261/2689, in apixaban and enoxaparin/warfarin groups, respectively. CI for event rate calculated based on Wald asymptotic confidence limits. Participants were categorized according to the actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban | Incidence of Adjudicated Major/CRNM Bleeding During the Treatment Period in Treated Participants | 0.0430 proportion of participants |
| Enoxaparin + Warfarin | Incidence of Adjudicated Major/CRNM Bleeding During the Treatment Period in Treated Participants | 0.0971 proportion of participants |
Comparison: Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint. Inferential testing was not conducted because the null hypothesis pertaining to superiority for VTE/VTE-related death was not rejected.p-value: <0.000195% CI: [0.3566, 0.5453]Cochran-Mantel-Haenszel
Secondary
Incidence of Adjudicated Minor Bleeding During the Treatment Period in Treated Participants
Bleeding defined by International Society on Thrombosis and Haemostasis: Minor bleeding: all acute clinically overt bleeding events not meeting the criteria for either major bleeding or CRNM. All events wre adjudicated by an ICAC blinded to treatment. Event rate (proportion of participants) calculated as n/N (n=number of participants with observation; N=Total number of participants in respective treatment group (all participants who received at least one dose of study drug). Participants were categorized to the treatment group to which they were assigned unless incorrect study treatment was received throughout the study, in which case the participant was categorized according to the treatment received.
Time frame: Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Population: Total number of participants receiving at least one dose of study drug n/N: 313/2676; 505/2689, in apixaban and enoxaparin/warfarin groups, respectively. CI for event rate calculated based on Wald asymptotic confidence limits. Participants were categorized according to the actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban | Incidence of Adjudicated Minor Bleeding During the Treatment Period in Treated Participants | 0.1170 proportion of participants |
| Enoxaparin + Warfarin | Incidence of Adjudicated Minor Bleeding During the Treatment Period in Treated Participants | 0.1878 proportion of participants |
Comparison: Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.p-value: <0.000195% CI: [0.5432, 0.7034]Cochran-Mantel-Haenszel
Secondary
Incidence of Adjudicated Symptomatic Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period
DVT adjudicated by an ICAC blinded to treatment. DVT evaluated by: compression ultrasound and/or venography. Includes events that occurred during the intended treatment period, regardless of whether the participant received study medication, intent to treat principle (ITT). Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants, excluding those with missing endpoint). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early).
Time frame: Day 1 up to 24 Weeks + 2 Days or 355 Days (Discontinued Early)
Population: Total number of participants in each randomized arm (ITT), excluding those with missing endpoint (n/N: 22/2608; 35/2633). CI for event rate calculated based on Wald asymptotic confidence limits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban | Incidence of Adjudicated Symptomatic Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period | 0.0084 proportion of participants |
| Enoxaparin + Warfarin | Incidence of Adjudicated Symptomatic Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period | 0.0133 proportion of participants |
Comparison: Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.95% CI: [0.3735, 1.0787]Cochran-Mantel-Haenszel
Secondary
Incidence of Adjudicated Symptomatic Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period
PE adjudicated by an ICAC blinded to treatment. PE: spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Includes events that occurred during the intended treatment period, regardless of whether the participant received study medication (ITT principle). Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants, excluding those with missing endpoint). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early).
Time frame: Day 1 to Week 24 + + 2 Days or 355 Days (Discontinued Early)
Population: Total number of participants in each randomized arm (ITT), excluding those with missing endpoint (n/N: 27/2606; 25/2632). CI for event rate calculated based on Wald asymptotic confidence limits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban | Incidence of Adjudicated Symptomatic Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period | 0.0104 proportion of participants |
| Enoxaparin + Warfarin | Incidence of Adjudicated Symptomatic Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period | 0.0095 proportion of participants |
Comparison: Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.95% CI: [0.6363, 1.8793]Cochran-Mantel-Haenszel
Secondary
Incidence of Adjudicated Total Bleeding During the Treatment Period in Treated Participants
Bleeding defined by International Society on Thrombosis and Haemostasis: Total Bleeding defined as any of major, CRNM, or minor bleeding. All events were adjudicated by an ICAC blinded to treatment. Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants in respective treatment group (all participants who received at least one dose of study drug). Participants were categorized to the treatment group to which they were assigned unless incorrect study treatment was received throughout the study, in which case the participant was categorized according to the treatment received.
Time frame: Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Population: Total number of participants receiving at least one dose of study drug n/N: 402/2676; 676/2689, in apixaban and enoxaparin/warfarin groups, respectively. CI for event rate calculated based on Wald asymptotic confidence limits. Participants were categorized according to the actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban | Incidence of Adjudicated Total Bleeding During the Treatment Period in Treated Participants | 0.1502 proportion of participants |
| Enoxaparin + Warfarin | Incidence of Adjudicated Total Bleeding During the Treatment Period in Treated Participants | 0.2514 proportion of participants |
Comparison: Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.p-value: <0.000195% CI: [0.5318, 0.6629]Cochran-Mantel-Haenszel
Secondary
Incidence of Adjudicated Venous Thromboembolism (VTE)-Related Death During the Intended Treatment Period
VTE-related death included: DVT-related death or PE-related death. All events were adjudicated by an ICAC blinded to treatment. DVT was assessed by compression ultrasound and/or venography; PE was assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of participants with observation; N=total number of participants in respective treatment groups excluding participants with missing endpoint information). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Includes events that occur during the intended treatment period regardless of whether or not the participant received study medication (ITT principle).
Time frame: Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Population: Total number of participants in respective treatment groups excluding participants with missing endpoint information. (n/N: 12/2608; 16/2630). CI for event rate calculated based on Wald asymptotic confidence limits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban | Incidence of Adjudicated Venous Thromboembolism (VTE)-Related Death During the Intended Treatment Period | 0.0046 proportion of participants |
| Enoxaparin + Warfarin | Incidence of Adjudicated Venous Thromboembolism (VTE)-Related Death During the Intended Treatment Period | 0.0061 proportion of participants |
Comparison: Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.95% CI: [0.356, 1.5889]Cochran-Mantel-Haenszel
Secondary
Incidence of All-Cause Death During the Intended Treatment Period
Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Includes events that occurred during the intended treatment period, regardless of whether the participant received study medication (ITT principle). Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants, excluding those with missing endpoint information).
Time frame: Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Population: Total number of participants excluding those with missing endpoint (n/N: 41/2608; 52/2630). Events included regardless of whether or not participant received treatment, ie, ITT principle. CI for event rate calculated based on Wald asymptotic confidence limits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban | Incidence of All-Cause Death During the Intended Treatment Period | 0.0157 proportion of participants |
| Enoxaparin + Warfarin | Incidence of All-Cause Death During the Intended Treatment Period | 0.0198 proportion of participants |
Comparison: Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.95% CI: [0.5287, 1.1906]Cochran-Mantel-Haenszel
Secondary
Incidence of Cardiovascular (CV)-Related Death Including VTE-related Death During the Intended Treatment Period
VTE-related death included: DVT-related death or PE-related death. All events were adjudicated by an ICAC blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of participants with observation; N=total number of participants in respective treatment groups excluding participants with missing endpoint information). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Includes events that occur during the intended treatment period regardless of whether or not the participant received study medication (ITT principle).
Time frame: Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Population: Total number of participants in respective groups excluding those with missing endpoint information (n/N: 15/2608; 23/2630). CI for event rate calculated based on Wald asymptotic confidence limits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban | Incidence of Cardiovascular (CV)-Related Death Including VTE-related Death During the Intended Treatment Period | 0.0058 proportion of participants |
| Enoxaparin + Warfarin | Incidence of Cardiovascular (CV)-Related Death Including VTE-related Death During the Intended Treatment Period | 0.0087 proportion of participants |
Comparison: Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.95% CI: [0.3419, 1.2508]Cochran-Mantel-Haenszel
Secondary
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Discontinuations Due to AEs and Death During the Treatment Period in Treated Participants
Treated Participants: all who received at least 1 dose of study drug. Participants categorized to the treatment group to which they were assigned unless incorrect study treatment was received throughout the study, in which case the participant was categorized according to treatment received. Included all SAEs and AEs with onset from first dose to last dose + 2 days (for AEs) or + 30 days (for SAEs); note; bleeding AEs and SAEs from first dose to last dose + 2 days included. Discontinuations due to AE included all AEs/SAEs from first dose until drug was discontinued. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Time frame: First dose to last dose of 24 Weeks + 2 days (AEs) or + 30 days (SAEs) or until drug discontinued
Population: Total number of participants receiving at least one dose of study drug. Participants were categorized according to the actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Discontinuations Due to AEs and Death During the Treatment Period in Treated Participants | SAE | 417 participants |
| Apixaban | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Discontinuations Due to AEs and Death During the Treatment Period in Treated Participants | Discontinued Due to AE or SAE | 162 participants |
| Apixaban | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Discontinuations Due to AEs and Death During the Treatment Period in Treated Participants | Bleeding AE or SAE | 415 participants |
| Apixaban | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Discontinuations Due to AEs and Death During the Treatment Period in Treated Participants | Death | 37 participants |
| Apixaban | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Discontinuations Due to AEs and Death During the Treatment Period in Treated Participants | AE | 1795 participants |
| Enoxaparin + Warfarin | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Discontinuations Due to AEs and Death During the Treatment Period in Treated Participants | Death | 44 participants |
| Enoxaparin + Warfarin | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Discontinuations Due to AEs and Death During the Treatment Period in Treated Participants | AE | 1923 participants |
| Enoxaparin + Warfarin | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Discontinuations Due to AEs and Death During the Treatment Period in Treated Participants | SAE | 410 participants |
| Enoxaparin + Warfarin | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Discontinuations Due to AEs and Death During the Treatment Period in Treated Participants | Bleeding AE or SAE | 695 participants |
| Enoxaparin + Warfarin | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Discontinuations Due to AEs and Death During the Treatment Period in Treated Participants | Discontinued Due to AE or SAE | 199 participants |
Secondary
Number of Treated Participants With Marked Abnormalities in Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests
Creatine kinase High: \>5\*ULN Units/Liter (U/L); Total Protein High/Low: \< 0.9 \*LLN or \> 1.1\*ULN, or if pre-dose \< LLN then use 0.9\* pre-dose or \> ULN if pre-dose \> ULN then use 1.1 \*pre-dose or \<LLN; Uric acid High: \> 1.5\* ULN, or if pre-dose \> ULN then use \> 2 \*pre-dose.
Time frame: Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Population: N=Treated participants who received at least one dose of study drug and had non-missing laboratory measurements.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban | Number of Treated Participants With Marked Abnormalities in Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests | Creatine Kinase High (N=2601, 2596) | 20 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests | Uric Acid High (N=2601, 2596) | 6 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests | Total Protein Low (N=2601, 2596) | 15 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests | Total Protein High (N=2601, 2596) | 0 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests | Total Protein High (N=2601, 2596) | 0 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests | Creatine Kinase High (N=2601, 2596) | 24 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests | Total Protein Low (N=2601, 2596) | 16 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests | Uric Acid High (N=2601, 2596) | 3 participants |
Secondary
Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests
Bicarbonate milliequivalents/Liter (mEq/L) Low/High: \< 0.75\*LLN or \> 1.25\*ULN, or if pre-dose \< LLN then use \< 0.75\*pre-dose or \> ULN if pre-dose \> ULN then use \> 1.25\*pre-dose or \< LLN; Serum Calcium mg/dL Low/High: \< 0.8\*LLN or \> 1.2\*ULN, or if pre-dose \< LLN then use \< 0.75\*pre-dose or \> ULN if pre-dose \> ULN then use \> 1.25\*pre-dose or \< LLN; Serum Chloride mEq/L: \< 0.9\*LLN or \> 1.1\*ULN, or if pre-dose \< LLN then use \< 0.9\*pre-dose or \> ULN if pre-dose \> ULN then use \> 1.1\*pre-dose or \< LLN; Serum Potassium mEq/L: \< 0.9\*LLN or \> 1.1\*ULN, or if pre-dose \< LLN then use \< 0.9\*pre-dose or \> ULN if pre-dose \> ULN then use \> 1.1\*pre-dose or \< LLN; Serum Sodium mEq/L: \< 0.95\*LLN or \> 1.05\*ULN, or if pre-dose \< LLN then use \< 0.95\*pre-dose or \> ULN if pre-dose \> ULN then use \> 1.05\*pre-dose or \< LLN.
Time frame: Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Population: N=Treated participants who received at least one dose of study drug and had non-missing laboratory measurements.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban | Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests | Total Calcium Low (N=2601,2596) | 3 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests | Chloride Low Total Calcium High (N=2601,2596) | 0 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests | Bicarbonate High (N=2600,2593) | 17 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests | Potassium Low (N=2601,2596) | 26 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests | Total Calcium High (N=2601,2596) | 12 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests | Potassium High (N=2601,2596) | 19 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests | Bicarbonate Low (N=2600,2593) | 44 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests | Sodium Low (N=2601,2596) | 10 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests | Chloride Low Total Calcium Low (N=2601,2596) | 5 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests | Sodium Low (N=2601,2596) | 4 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests | Chloride Low Total Calcium Low (N=2601,2596) | 3 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests | Bicarbonate Low (N=2600,2593) | 31 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests | Bicarbonate High (N=2600,2593) | 11 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests | Total Calcium Low (N=2601,2596) | 10 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests | Total Calcium High (N=2601,2596) | 11 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests | Sodium Low (N=2601,2596) | 4 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests | Chloride Low Total Calcium High (N=2601,2596) | 1 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests | Potassium Low (N=2601,2596) | 22 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests | Potassium High (N=2601,2596) | 22 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests | Sodium Low (N=2601,2596) | 6 participants |
Secondary
Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests
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). White blood cells: \< 0.75\*LLN, \> 1.25\*ULN; Hemoglobin: \<= 11.5 g/dL (males), \<= 9.5 g/dL (females); Hematocrit: \<= 37% (males), \<= 32% (females); Erythrocytes: \<0.75\*10\^6 c/µL\*PreRx; Platelet count: \< 75\*10\^9 c/L, \> 700\*10\^9 c/L; ANC: \< 1.00\*10\^3 c/µL; Abs eosinophils: \> 0.750\*10\^3 c/µL; Abs Basophils: \> 400/MM\^3; Abs Monocytes\> 2000/MM\^3; Abs Lymphocytes: \< 0.750\*10\*3 c/ µL, \> 7.5\*10\^3 c/ µL.
Time frame: Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Population: N=Treated participants who received at least one dose of study drug and had non-missing laboratory measurements.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Erthrocytes Low (N=2599, 2593) | 23 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Hematocrit Low (N=2588, 2587) | 26 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Hemoglobin Low (N=2599, 2593) | 96 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Platelet Count Low (N=2594, 2589) | 23 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Leukocytes Low (N=2528, 2519) | 41 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Leukocytes High (N=2528, 2519) | 26 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Absolute Basophils High (N=2594,2589) | 1 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Absolute Eosinophils High (N=2594,2589) | 84 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Absolute Lyphocytes Low (N=2594,2589) | 94 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Absolute Lyphocytes High (N=2594,2589) | 4 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Absolute Monocytes High (N=2594,2589) | 1 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Absolute Neutrophils Low (N=2594,2589) | 9 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Absolute Monocytes High (N=2594,2589) | 2 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Erthrocytes Low (N=2599, 2593) | 17 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Absolute Basophils High (N=2594,2589) | 2 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Hematocrit Low (N=2588, 2587) | 20 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Absolute Lyphocytes High (N=2594,2589) | 3 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Hemoglobin Low (N=2599, 2593) | 101 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Absolute Eosinophils High (N=2594,2589) | 79 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Platelet Count Low (N=2594, 2589) | 13 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Absolute Neutrophils Low (N=2594,2589) | 20 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Leukocytes Low (N=2528, 2519) | 41 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Absolute Lyphocytes Low (N=2594,2589) | 76 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests | Leukocytes High (N=2528, 2519) | 15 participants |
Secondary
Number of Treated Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests
Blood urea nitrogen (BUN), milligrams/deciliter (mg/dL), units per liter (U/L). BUN mg/dL High: \> 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.
Time frame: Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Population: N=Treated participants who received at least one dose of study drug and had non-missing laboratory measurements.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban | Number of Treated Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests | ALT High (N=2601, 2598) | 52 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests | AST High (N=2601, 2598) | 40 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests | Creatinine High (N=2601, 2596) | 47 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests | Direct Bilirubin High (N=2601, 2593) | 28 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests | ALP High (N=2601, 2598) | 35 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests | Total Bilirubin High (N=2601, 2597) | 8 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests | BUN High (N=517, 523) | 2 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests | Total Bilirubin High (N=2601, 2597) | 7 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests | BUN High (N=517, 523) | 7 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests | Creatinine High (N=2601, 2596) | 37 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests | ALT High (N=2601, 2598) | 145 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests | ALP High (N=2601, 2598) | 27 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests | AST High (N=2601, 2598) | 40 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests | Direct Bilirubin High (N=2601, 2593) | 21 participants |
Secondary
Number of Treated Participants With Marked Abnormalities in Urinalysis Laboratory Tests
All tests in urine: Glucose: If missing pre-dose use ≥ 2, or if value ≥ 4, or if pre-dose = 0 or 0.5 use ≥ 2, or if pre-dose = 1 use ≥ 3, or if pre-dose = 2 or 3 use ≥ 4; Protein: If missing pre-dose use ≥ 2, or if value ≥ 4, or if pre-dose = 0 or 0.5 use ≥ 2, or if pre-dose = 1 use ≥ 3, or if pre-dose = 2 or 3 use ≥ 4; Blood: If missing pre-dose use ≥ 2, or if value ≥ 4, or if pre-dose = 0 or 0.5 use ≥ 2, or if pre-dose = 1 use ≥ 3, or if pre-dose = 2 or 3 use ≥ 4; Leukocyte esterase: If missing pre-dose use ≥ 2, or if value ≥ 4, or if pre-dose = 0 or 0.5 use ≥ 2, or if pre-dose = 1 use ≥ 3, or if pre-dose = 2 or 3 use ≥ 4;Red blood cells (RBC): If missing pre-dose use ≥ 2, or if value ≥ 4, or if pre-dose = 0 or 0.5 use ≥ 2, or if pre-dose = 1 use ≥ 3, or if pre-dose = 2 or 3 use ≥ 4; White blood cells (WBC): If missing pre-dose use ≥ 2, or if value ≥ 4, or if pre-dose = 0 or 0.5 use ≥ 2, or if pre-dose = 1 use ≥ 3, or if pre-dose = 2 or 3 use ≥ 4.
Time frame: Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Population: N=Treated participants who received at least one dose of study drug and had non-missing laboratory measurements.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban | Number of Treated Participants With Marked Abnormalities in Urinalysis Laboratory Tests | Leukocyte Esterase in Urine High (N=2289, 2273) | 105 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Urinalysis Laboratory Tests | RBC + WBC in Urine High (N=1685, 1719) | 359 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Urinalysis Laboratory Tests | Glucose in Urine High (N=2289, 2273) | 46 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Urinalysis Laboratory Tests | RBC in Urine High (N=1293, 1389) | 111 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Urinalysis Laboratory Tests | Protein in Urine High (N=2289, 2273) | 41 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Urinalysis Laboratory Tests | WBC in Urine High (N=1354, 1361) | 274 participants |
| Apixaban | Number of Treated Participants With Marked Abnormalities in Urinalysis Laboratory Tests | Blood in Urine High (N=2289, 2273) | 85 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Urinalysis Laboratory Tests | WBC in Urine High (N=1354, 1361) | 263 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Urinalysis Laboratory Tests | Blood in Urine High (N=2289, 2273) | 127 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Urinalysis Laboratory Tests | Glucose in Urine High (N=2289, 2273) | 31 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Urinalysis Laboratory Tests | Leukocyte Esterase in Urine High (N=2289, 2273) | 102 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Urinalysis Laboratory Tests | Protein in Urine High (N=2289, 2273) | 50 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Urinalysis Laboratory Tests | RBC + WBC in Urine High (N=1685, 1719) | 361 participants |
| Enoxaparin + Warfarin | Number of Treated Participants With Marked Abnormalities in Urinalysis Laboratory Tests | RBC in Urine High (N=1293, 1389) | 140 participants |