Venous Thromboembolism
Conditions
Keywords
VTE, thromboembolism, thrombosis, embolism, apixaban, Eliquis
Brief summary
To assess the safety and descriptive efficacy of apixaban in pediatric subjects requiring anticoagulation for the treatment of a VTE.
Interventions
DRUGApixaban
Tablet or Solution
DRUGStandard of Care
Unfractionated heparin, low molecular weight heparin, and/or a vitamin K antagonist. For subjects under 2 years of age, standard of care will be limited to unfractionated heparin or low molecular weight heparin.
Sponsors
Pfizer
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Days to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Birth to \<18 years of age with a minimum weight of 2.6 kg at the time of randomization. 2. Presence of an index VTE which is confirmed by imaging. 3. Intention to manage the index VTE with anticoagulation treatment for at least 6 to 12 weeks. 4. Subjects able to tolerate oral feeding, nasogastric (NG), gastric (G) feeding and are currently tolerating enteric medications, as per investigator's judgement.
Exclusion criteria
1. Anticoagulant treatment for the index VTE for greater than 14 days prior to randomization. Neonates that are enrolled into the PK cohort must be on a minimum of 5 days and a maximum of 14 days SOC anticoagulation prior to randomization. Neonates that are enrolled into the post PK cohort may receive SOC anticoagulation for up to 14 days prior to randomization. 2. Thrombectomy, thrombolytic therapy, or insertion of a caval filter to treat the index VTE. 3. A mechanical heart valve. 4. Active bleeding or high risk of bleeding at the time of randomization. 5. Intracranial bleed, including intraventricular hemorrhage, within 3 months prior to randomization. 6. Abnormal baseline liver function at randomization. 7. Inadequate renal function at the time of randomization. 8. Platelet count \<50×109 per L at randomization. 9. Uncontrolled severe hypertension at the time of randomization. 10. Use of prohibited concomitant medication at the time of randomization. 11. Female subjects who are either pregnant or breastfeeding a child. 12. Use of aggressive life-saving therapies such as ventricular assist devices (VAD) or extracorporeal membrane oxygenation (ECMO) at the time of enrollment. 13. Unable to take oral or enteric medication via the NG or G tube. 14. Known inherited or acquired antiphospholipid syndrome (APS). 15. Known inherited bleeding disorder or coagulopathy with increased bleeding risk (eg, hemophilia, von Willebrand disease, etc.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Composite of Major and Clinically Relevant Non-Major (CRNM) Bleeding | From first dose (Day 1) up to 114 days | Bleeding definitions are based on the Perinatal and Paediatric Haemostasis Subcommittee of the International Society on Thrombosis and Haemostasis (ISTH) criteria. Major bleeding includes: (i) fatal bleeding; (ii) clinically overt bleeding with a decrease in Hgb of at least 20 g/L (2 g/dL) in 24 hours; (iii) retroperitoneal, pulmonary, intracranial, or central nervous system bleeding; and (iv) bleeding requiring surgical intervention in an operating suite (including interventional radiology). Clinically relevant non-major bleeding includes: (i) overt bleeding requiring a blood product not attributable to the participant's underlying condition; and (ii) bleeding requiring medical or surgical intervention to restore hemostasis, other than in an operating suite. |
| Percentage of Participants With Symptomatic and Asymptomatic Recurrent Venous Thromboembolism (VTE) and VTE-Related Mortality | From first dose (Day 1) up to 114 days | Recurrent VTE, defined as either contiguous progression or non-contiguous new thrombus and including, but not limited to deep vein thrombosis (DVT), pulmonary embolism (PE) and paradoxical embolism. 95% CI was from the Agresti-Coull method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Index Venous Thromboembolism (VTE) Status | From first dose (Day 1) up to 91 days | Index VTE status was defined as the last image obtained during the Main treatment phase for each participant's comparison to baseline imaging. Index VTE status was classified as Recurrence-contiguous; Recurrence-new; Unchanged; Regression; Resolution; Indeterminate/Nondiagnostic. Participants could have multiple concomitant index events. Regression was defined as (ie, unequivocal decrease \[\>50%\] of the total volume/mass of the thrombus compared to the index event) |
| Percentage of Participants With Stroke | From first dose (Day 1) up to 114 days | Participants were assessed for incidence of stroke. |
| Percentage of Participants With Symptomatic and Asymptomatic Recurrent Venous Thromboembolism (VTE) | From first dose (Day 1) up to 114 days | Recurrent VTE, defined as either contiguous progression or non-contiguous new thrombus and including, but not limited to deep vein thrombosis (DVT), pulmonary embolism (PE) and paradoxical embolism. 95% CI was from the Agresti-Coull method. |
| Number of Participants With New Symptomatic or Asymptomatic Deep Vein Thrombosis (DVT) and New Symptomatic or Asymptomatic Pulmonary Embolism (PE) | From first dose (Day 1) up to 114 days | Participants were assessed for incidence of Symptomatic or Asymptomatic Deep Vein Thrombosis (DVT) and New Symptomatic or Asymptomatic Pulmonary Embolism (PE). |
| Percentage of Participants Who Died | From first dose (Day 1) up to 114 days | Death due to any cause was assessed. 95% CI was calculated using the Agresti-Coull method. |
| Number of Participants With Clinically Relevant Non-Major (CRNM) Bleeding, Major Bleeding and Minor Bleeding | From first dose (Day 1) up to 114 days | Bleeding definitions are based on the Perinatal and Paediatric Haemostasis Subcommittee of the International Society on Thrombosis and Haemostasis (ISTH) criteria. Major bleeding includes: (i) fatal bleeding; (ii) clinically overt bleeding with a decrease in Hgb of at least 20 g/L (2 g/dL) in 24 hours; (iii) retroperitoneal, pulmonary, intracranial, or central nervous system bleeding; and (iv) bleeding requiring surgical intervention in an operating suite (including interventional radiology). Clinically relevant non-major bleeding includes: (i) overt bleeding requiring a blood product not attributable to the participant's underlying condition; and (ii) bleeding requiring medical or surgical intervention to restore hemostasis, other than in an operating suite. Minor bleeding was defined as any overt or macroscopic evidence of bleeding that does not fulfill the above criteria for either major bleeding or clinically relevant, non-major bleeding. |
| Blood Concentration of Apixaban (ng/mL) | 3 hour (H), 12 H, 24 H at Day 3; pre and post dose at Day 14 and Day 42 | Blood samples were collected to assess the apixaban concentration at specified timepoints. Day 1 PK concentrations were only collected for participants in the Birth to ≤27 days arm. The lower limit of quantification (LLOQ) is 1.0 ng/mL for plasma samples, and 0.5 ng/mL for dried blood samples. |
| Concentration of Plasma Anti-Factor Xa (ng/mL) | Pre and post dose at Day 14 and Day 42 | Blood samples were collected to assess the Anti-Factor Xa concentration at specified timepoints. Day 1 PK concentrations were only collected for participants in the Birth to ≤27 days arm. The lower limit of quantification (LLOQ) is 35.0 ng/mL. |
| Percentage of Participants With Other Symptomatic and Asymptomatic Venous Thromboembolism (VTE) | From first dose (Day 1) up to 114 days | Other VTE included events such as cerebral sinovenous thrombosis, renal vein thrombosis, portal vein thrombosis, catheter-related VTE, and splanchnic thrombosis. If VTE event type was blank, it was included in the Other VTE. 95% CI was from the Agresti-Coull method. |
| Percentage of Participants With Venous Thromboembolism (VTE)-Related Mortality | From first dose (Day 1) up to 114 days | Participants were assessed for death due to Venous Thromboembolism (VTE). |
Countries
Australia, Austria, Canada, France, Germany, Israel, Mexico, Russia, Spain, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participants Receiving Apixaban Participants between birth to \<18 years were dosed on a body weight tiered regimen. Subjects ≥35kg received 10mg twice daily(BID) for 7 days followed by 5mg BID thereafter;\<35kg to 25kg received 8mg BID for 7 days followed by 4mg BID thereafter;\<25 to 18kg received 6mg BID for 7 days and then 3mg BID thereafter;\<18 to 12kg received 4mg BID for 7 days and then 2mg BID thereafter;\<12 to 9kg received 3mg BID for 7 days and then 1.5mg BID thereafter;\< 9kg to 6kg received 2 mg BID for 7 days and 1mg BID thereafter;\<6kg to 5kg received 1mg BID for 7 days and 0.5mg BID thereafter;\<5kg to 4kg received 0.6mg twice daily for 7 days and 0.3mg BID thereafter; For sub group analysis, PK cohort neonates ≥ 2.6kg received 0.1mg BID. Dose was adjusted as determined by PK measurements (i.e., to 0.2mg BID, 0.1mg daily or dose stay the same).For the post PK cohort Neonates ˂4kg to 2.6kg, if confirmed by PK sub analysis ,participants received 0.2mg BID for 7 days and 0.1mg BID thereafter. | 155 |
| Participants Treated With Standard of Care Participants were treated with unfractionated heparin, low molecular weight heparin, and/or a vitamin K antagonist. For participants under 2 years of age, standard of care was limited to unfractionated heparin or low molecular weight heparin. | 74 |
| Total | 229 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Extension Phase (Day 85 to Day 168) | Adverse Event | 1 | 0 |
| Extension Phase (Day 85 to Day 168) | Other Reasons | 1 | 0 |
| Extension Phase (Day 85 to Day 168) | Withdrawal by Parent/Guardian | 1 | 0 |
| Main Phase (Day 1 to Day 84) | Adverse Event | 7 | 0 |
| Main Phase (Day 1 to Day 84) | Death | 1 | 1 |
| Main Phase (Day 1 to Day 84) | Entrance Criteria | 1 | 1 |
| Main Phase (Day 1 to Day 84) | Lost to Follow-up | 3 | 0 |
| Main Phase (Day 1 to Day 84) | No Longer Meets Eligibility Criteria | 0 | 1 |
| Main Phase (Day 1 to Day 84) | Other Reasons | 4 | 2 |
| Main Phase (Day 1 to Day 84) | Withdrawal by Parent/Guardian | 0 | 4 |
| Main Phase (Day 1 to Day 84) | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Participants Receiving Apixaban | Participants Treated With Standard of Care | Total |
|---|---|---|---|
| Age, Continuous | 11.10 years STANDARD_DEVIATION 6.51 | 11.68 years STANDARD_DEVIATION 6.02 | 11.29 years STANDARD_DEVIATION 6.35 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 13 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 143 Participants | 61 Participants | 204 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 4 Participants | 9 Participants |
| Race/Ethnicity, Customized Black | 22 Participants | 9 Participants | 31 Participants |
| Race/Ethnicity, Customized Multiracial | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 6 Participants | 5 Participants | 11 Participants |
| Race/Ethnicity, Customized White | 120 Participants | 55 Participants | 175 Participants |
| Sex: Female, Male Female | 85 Participants | 43 Participants | 128 Participants |
| Sex: Female, Male Male | 70 Participants | 31 Participants | 101 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 155 | 1 / 74 |
| other Total, other adverse events | 132 / 152 | 59 / 73 |
| serious Total, serious adverse events | 40 / 152 | 17 / 73 |
Outcome results
Primary
Percentage of Participants With Composite of Major and Clinically Relevant Non-Major (CRNM) Bleeding
Bleeding definitions are based on the Perinatal and Paediatric Haemostasis Subcommittee of the International Society on Thrombosis and Haemostasis (ISTH) criteria. Major bleeding includes: (i) fatal bleeding; (ii) clinically overt bleeding with a decrease in Hgb of at least 20 g/L (2 g/dL) in 24 hours; (iii) retroperitoneal, pulmonary, intracranial, or central nervous system bleeding; and (iv) bleeding requiring surgical intervention in an operating suite (including interventional radiology). Clinically relevant non-major bleeding includes: (i) overt bleeding requiring a blood product not attributable to the participant's underlying condition; and (ii) bleeding requiring medical or surgical intervention to restore hemostasis, other than in an operating suite.
Time frame: From first dose (Day 1) up to 114 days
Population: The safety data set (as-treated) consist of all randomized participants who received at least one dose of study drug. 95% CI was calculated using the Agresti-Coull method.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving Apixaban | Percentage of Participants With Composite of Major and Clinically Relevant Non-Major (CRNM) Bleeding | 1.3 percentage of participants |
| Participants Treated With Standard of Care | Percentage of Participants With Composite of Major and Clinically Relevant Non-Major (CRNM) Bleeding | 1.4 percentage of participants |
Primary
Percentage of Participants With Symptomatic and Asymptomatic Recurrent Venous Thromboembolism (VTE) and VTE-Related Mortality
Recurrent VTE, defined as either contiguous progression or non-contiguous new thrombus and including, but not limited to deep vein thrombosis (DVT), pulmonary embolism (PE) and paradoxical embolism. 95% CI was from the Agresti-Coull method.
Time frame: From first dose (Day 1) up to 114 days
Population: The Full Analysis Set contains all randomized participants and also those assigned to apixaban post-protocol amendment 8.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving Apixaban | Percentage of Participants With Symptomatic and Asymptomatic Recurrent Venous Thromboembolism (VTE) and VTE-Related Mortality | 2.6 percentage of participants |
| Participants Treated With Standard of Care | Percentage of Participants With Symptomatic and Asymptomatic Recurrent Venous Thromboembolism (VTE) and VTE-Related Mortality | 2.7 percentage of participants |
Secondary
Blood Concentration of Apixaban (ng/mL)
Blood samples were collected to assess the apixaban concentration at specified timepoints. Day 1 PK concentrations were only collected for participants in the Birth to ≤27 days arm. The lower limit of quantification (LLOQ) is 1.0 ng/mL for plasma samples, and 0.5 ng/mL for dried blood samples.
Time frame: 3 hour (H), 12 H, 24 H at Day 3; pre and post dose at Day 14 and Day 42
Population: The PK analysis population is defined as all participants randomized to and treated with apixaban who have at least 1 concentration of apixaban. Participants with sample size of quantifiable values (≥ LLOQ) at the specified timepoints were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Receiving Apixaban | Blood Concentration of Apixaban (ng/mL) | Pre-dose at Day 42 | 54.5 nanogram per millilitre (ng/mL) | Standard Deviation 33.7 |
| Participants Receiving Apixaban | Blood Concentration of Apixaban (ng/mL) | Post-Dose at Day 42 | 151 nanogram per millilitre (ng/mL) | Standard Deviation 79.1 |
| Participants Receiving Apixaban | Blood Concentration of Apixaban (ng/mL) | Pre-dose at Day 14 | 61.1 nanogram per millilitre (ng/mL) | Standard Deviation 53.7 |
| Participants Receiving Apixaban | Blood Concentration of Apixaban (ng/mL) | Post-dose at Day 14 | 152 nanogram per millilitre (ng/mL) | Standard Deviation 80.2 |
| Participants Treated With Standard of Care | Blood Concentration of Apixaban (ng/mL) | Post-Dose at Day 42 | 212 nanogram per millilitre (ng/mL) | Standard Deviation 89.8 |
| Participants Treated With Standard of Care | Blood Concentration of Apixaban (ng/mL) | Pre-dose at Day 14 | 72.7 nanogram per millilitre (ng/mL) | Standard Deviation 42.5 |
| Participants Treated With Standard of Care | Blood Concentration of Apixaban (ng/mL) | Pre-dose at Day 42 | 67.9 nanogram per millilitre (ng/mL) | Standard Deviation 33.8 |
| Participants Treated With Standard of Care | Blood Concentration of Apixaban (ng/mL) | Post-dose at Day 14 | 189 nanogram per millilitre (ng/mL) | Standard Deviation 61 |
| Participants With Age 28 Days - < 2 Years | Blood Concentration of Apixaban (ng/mL) | Post-dose at Day 14 | 203 nanogram per millilitre (ng/mL) | Standard Deviation 118 |
| Participants With Age 28 Days - < 2 Years | Blood Concentration of Apixaban (ng/mL) | Post-Dose at Day 42 | 143 nanogram per millilitre (ng/mL) | Standard Deviation 88 |
| Participants With Age 28 Days - < 2 Years | Blood Concentration of Apixaban (ng/mL) | Pre-dose at Day 42 | 123 nanogram per millilitre (ng/mL) | Standard Deviation 123 |
| Participants With Age 28 Days - < 2 Years | Blood Concentration of Apixaban (ng/mL) | Pre-dose at Day 14 | 56.4 nanogram per millilitre (ng/mL) | Standard Deviation 65.6 |
| Participants in Age Group-Birth - ≤ 27 Days | Blood Concentration of Apixaban (ng/mL) | Post-Dose at Day 42 | 109 nanogram per millilitre (ng/mL) | Standard Deviation 56 |
| Participants in Age Group-Birth - ≤ 27 Days | Blood Concentration of Apixaban (ng/mL) | Hour 12 at Day 1 | 13.9 nanogram per millilitre (ng/mL) | Standard Deviation 5.7 |
| Participants in Age Group-Birth - ≤ 27 Days | Blood Concentration of Apixaban (ng/mL) | Hour 24 at Day 1 | 23.3 nanogram per millilitre (ng/mL) | Standard Deviation 10.1 |
| Participants in Age Group-Birth - ≤ 27 Days | Blood Concentration of Apixaban (ng/mL) | Pre-dose at Day 14 | 48.3 nanogram per millilitre (ng/mL) | Standard Deviation 23 |
| Participants in Age Group-Birth - ≤ 27 Days | Blood Concentration of Apixaban (ng/mL) | Post-dose at Day 14 | 119 nanogram per millilitre (ng/mL) | Standard Deviation 45.7 |
| Participants in Age Group-Birth - ≤ 27 Days | Blood Concentration of Apixaban (ng/mL) | Pre-dose at Day 42 | 50.2 nanogram per millilitre (ng/mL) | Standard Deviation 34.1 |
| Participants in Age Group-Birth - ≤ 27 Days | Blood Concentration of Apixaban (ng/mL) | Hour 3 at Day 1 | 30.7 nanogram per millilitre (ng/mL) | Standard Deviation 12.9 |
Secondary
Concentration of Plasma Anti-Factor Xa (ng/mL)
Blood samples were collected to assess the Anti-Factor Xa concentration at specified timepoints. Day 1 PK concentrations were only collected for participants in the Birth to ≤27 days arm. The lower limit of quantification (LLOQ) is 35.0 ng/mL.
Time frame: Pre and post dose at Day 14 and Day 42
Population: The PK analysis population is defined as all participants randomized to and treated with apixaban who have at least 1 concentration of apixaban. Participants with sample size of quantifiable values (≥ LLOQ) at the specified timepoints were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Receiving Apixaban | Concentration of Plasma Anti-Factor Xa (ng/mL) | Post-dose at Day 14 | 147 nanogram per millilitre (ng/mL) | Standard Deviation 83.5 |
| Participants Receiving Apixaban | Concentration of Plasma Anti-Factor Xa (ng/mL) | Pre-dose at Day 14 | 72.7 nanogram per millilitre (ng/mL) | Standard Deviation 60.4 |
| Participants Receiving Apixaban | Concentration of Plasma Anti-Factor Xa (ng/mL) | Pre-dose at Day 42 | 63.9 nanogram per millilitre (ng/mL) | Standard Deviation 27.4 |
| Participants Receiving Apixaban | Concentration of Plasma Anti-Factor Xa (ng/mL) | Post-Dose at Day 42 | 153 nanogram per millilitre (ng/mL) | Standard Deviation 84.9 |
| Participants Treated With Standard of Care | Concentration of Plasma Anti-Factor Xa (ng/mL) | Post-Dose at Day 42 | 220 nanogram per millilitre (ng/mL) | Standard Deviation 98.4 |
| Participants Treated With Standard of Care | Concentration of Plasma Anti-Factor Xa (ng/mL) | Pre-dose at Day 14 | 82.7 nanogram per millilitre (ng/mL) | Standard Deviation 41.3 |
| Participants Treated With Standard of Care | Concentration of Plasma Anti-Factor Xa (ng/mL) | Post-dose at Day 14 | 202 nanogram per millilitre (ng/mL) | Standard Deviation 75.8 |
| Participants Treated With Standard of Care | Concentration of Plasma Anti-Factor Xa (ng/mL) | Pre-dose at Day 42 | 75.3 nanogram per millilitre (ng/mL) | Standard Deviation 31 |
| Participants With Age 28 Days - < 2 Years | Concentration of Plasma Anti-Factor Xa (ng/mL) | Post-dose at Day 14 | 190 nanogram per millilitre (ng/mL) | Standard Deviation 105 |
| Participants With Age 28 Days - < 2 Years | Concentration of Plasma Anti-Factor Xa (ng/mL) | Post-Dose at Day 42 | 156 nanogram per millilitre (ng/mL) | Standard Deviation 92.2 |
| Participants With Age 28 Days - < 2 Years | Concentration of Plasma Anti-Factor Xa (ng/mL) | Pre-dose at Day 42 | 53.5 nanogram per millilitre (ng/mL) | Standard Deviation 13.4 |
| Participants With Age 28 Days - < 2 Years | Concentration of Plasma Anti-Factor Xa (ng/mL) | Pre-dose at Day 14 | 74.7 nanogram per millilitre (ng/mL) | Standard Deviation 69.7 |
| Participants in Age Group-Birth - ≤ 27 Days | Concentration of Plasma Anti-Factor Xa (ng/mL) | Post-Dose at Day 42 | 101 nanogram per millilitre (ng/mL) | — |
| Participants in Age Group-Birth - ≤ 27 Days | Concentration of Plasma Anti-Factor Xa (ng/mL) | Pre-dose at Day 14 | 48.0 nanogram per millilitre (ng/mL) | Standard Deviation 1 |
| Participants in Age Group-Birth - ≤ 27 Days | Concentration of Plasma Anti-Factor Xa (ng/mL) | Post-dose at Day 14 | 127 nanogram per millilitre (ng/mL) | Standard Deviation 4.04 |
Secondary
Number of Participants With Clinically Relevant Non-Major (CRNM) Bleeding, Major Bleeding and Minor Bleeding
Bleeding definitions are based on the Perinatal and Paediatric Haemostasis Subcommittee of the International Society on Thrombosis and Haemostasis (ISTH) criteria. Major bleeding includes: (i) fatal bleeding; (ii) clinically overt bleeding with a decrease in Hgb of at least 20 g/L (2 g/dL) in 24 hours; (iii) retroperitoneal, pulmonary, intracranial, or central nervous system bleeding; and (iv) bleeding requiring surgical intervention in an operating suite (including interventional radiology). Clinically relevant non-major bleeding includes: (i) overt bleeding requiring a blood product not attributable to the participant's underlying condition; and (ii) bleeding requiring medical or surgical intervention to restore hemostasis, other than in an operating suite. Minor bleeding was defined as any overt or macroscopic evidence of bleeding that does not fulfill the above criteria for either major bleeding or clinically relevant, non-major bleeding.
Time frame: From first dose (Day 1) up to 114 days
Population: The safety data set (as-treated) consist of all randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants Receiving Apixaban | Number of Participants With Clinically Relevant Non-Major (CRNM) Bleeding, Major Bleeding and Minor Bleeding | Major Bleeding | 0 Participants |
| Participants Receiving Apixaban | Number of Participants With Clinically Relevant Non-Major (CRNM) Bleeding, Major Bleeding and Minor Bleeding | Clinically Relevant Non-major Bleeding | 2 Participants |
| Participants Receiving Apixaban | Number of Participants With Clinically Relevant Non-Major (CRNM) Bleeding, Major Bleeding and Minor Bleeding | Minor Bleeding | 54 Participants |
| Participants Treated With Standard of Care | Number of Participants With Clinically Relevant Non-Major (CRNM) Bleeding, Major Bleeding and Minor Bleeding | Major Bleeding | 0 Participants |
| Participants Treated With Standard of Care | Number of Participants With Clinically Relevant Non-Major (CRNM) Bleeding, Major Bleeding and Minor Bleeding | Clinically Relevant Non-major Bleeding | 1 Participants |
| Participants Treated With Standard of Care | Number of Participants With Clinically Relevant Non-Major (CRNM) Bleeding, Major Bleeding and Minor Bleeding | Minor Bleeding | 21 Participants |
Secondary
Number of Participants With Index Venous Thromboembolism (VTE) Status
Index VTE status was defined as the last image obtained during the Main treatment phase for each participant's comparison to baseline imaging. Index VTE status was classified as Recurrence-contiguous; Recurrence-new; Unchanged; Regression; Resolution; Indeterminate/Nondiagnostic. Participants could have multiple concomitant index events. Regression was defined as (ie, unequivocal decrease \[\>50%\] of the total volume/mass of the thrombus compared to the index event)
Time frame: From first dose (Day 1) up to 91 days
Population: The Full Analysis Set contains all randomized participants and also those assigned to apixaban post-PA8. Excluding participants with a negative or Non-Diagnostic Index Event
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants Receiving Apixaban | Number of Participants With Index Venous Thromboembolism (VTE) Status | Recurrence-contiguous | 2 Participants |
| Participants Receiving Apixaban | Number of Participants With Index Venous Thromboembolism (VTE) Status | Recurrence-new | 0 Participants |
| Participants Receiving Apixaban | Number of Participants With Index Venous Thromboembolism (VTE) Status | Unchanged | 8 Participants |
| Participants Receiving Apixaban | Number of Participants With Index Venous Thromboembolism (VTE) Status | Regression | 25 Participants |
| Participants Receiving Apixaban | Number of Participants With Index Venous Thromboembolism (VTE) Status | Resolution | 77 Participants |
| Participants Receiving Apixaban | Number of Participants With Index Venous Thromboembolism (VTE) Status | Indeterminate/Nondiagnostic | 15 Participants |
| Participants Receiving Apixaban | Number of Participants With Index Venous Thromboembolism (VTE) Status | Missing Follow-up Imaging, therefore cannot compare to baseline | 5 Participants |
| Participants Receiving Apixaban | Number of Participants With Index Venous Thromboembolism (VTE) Status | Imaging not completed within the specified time period | 6 Participants |
| Participants Treated With Standard of Care | Number of Participants With Index Venous Thromboembolism (VTE) Status | Imaging not completed within the specified time period | 1 Participants |
| Participants Treated With Standard of Care | Number of Participants With Index Venous Thromboembolism (VTE) Status | Recurrence-contiguous | 0 Participants |
| Participants Treated With Standard of Care | Number of Participants With Index Venous Thromboembolism (VTE) Status | Resolution | 36 Participants |
| Participants Treated With Standard of Care | Number of Participants With Index Venous Thromboembolism (VTE) Status | Recurrence-new | 0 Participants |
| Participants Treated With Standard of Care | Number of Participants With Index Venous Thromboembolism (VTE) Status | Missing Follow-up Imaging, therefore cannot compare to baseline | 8 Participants |
| Participants Treated With Standard of Care | Number of Participants With Index Venous Thromboembolism (VTE) Status | Unchanged | 6 Participants |
| Participants Treated With Standard of Care | Number of Participants With Index Venous Thromboembolism (VTE) Status | Indeterminate/Nondiagnostic | 7 Participants |
| Participants Treated With Standard of Care | Number of Participants With Index Venous Thromboembolism (VTE) Status | Regression | 11 Participants |
Secondary
Number of Participants With New Symptomatic or Asymptomatic Deep Vein Thrombosis (DVT) and New Symptomatic or Asymptomatic Pulmonary Embolism (PE)
Participants were assessed for incidence of Symptomatic or Asymptomatic Deep Vein Thrombosis (DVT) and New Symptomatic or Asymptomatic Pulmonary Embolism (PE).
Time frame: From first dose (Day 1) up to 114 days
Population: The Full Analysis Set contains all randomized participants and also those assigned to apixaban post-PA8.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants Receiving Apixaban | Number of Participants With New Symptomatic or Asymptomatic Deep Vein Thrombosis (DVT) and New Symptomatic or Asymptomatic Pulmonary Embolism (PE) | New Symptomatic or Asymptomatic DVT | 1 Participants |
| Participants Receiving Apixaban | Number of Participants With New Symptomatic or Asymptomatic Deep Vein Thrombosis (DVT) and New Symptomatic or Asymptomatic Pulmonary Embolism (PE) | New Symptomatic or Asymptomatic PE | 0 Participants |
| Participants Treated With Standard of Care | Number of Participants With New Symptomatic or Asymptomatic Deep Vein Thrombosis (DVT) and New Symptomatic or Asymptomatic Pulmonary Embolism (PE) | New Symptomatic or Asymptomatic DVT | 1 Participants |
| Participants Treated With Standard of Care | Number of Participants With New Symptomatic or Asymptomatic Deep Vein Thrombosis (DVT) and New Symptomatic or Asymptomatic Pulmonary Embolism (PE) | New Symptomatic or Asymptomatic PE | 0 Participants |
Secondary
Percentage of Participants Who Died
Death due to any cause was assessed. 95% CI was calculated using the Agresti-Coull method.
Time frame: From first dose (Day 1) up to 114 days
Population: The Full Analysis Set contains all randomized participants and also those assigned to apixaban post-PA8.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving Apixaban | Percentage of Participants Who Died | 1.3 percentage of participants |
| Participants Treated With Standard of Care | Percentage of Participants Who Died | 1.4 percentage of participants |
Secondary
Percentage of Participants With Other Symptomatic and Asymptomatic Venous Thromboembolism (VTE)
Other VTE included events such as cerebral sinovenous thrombosis, renal vein thrombosis, portal vein thrombosis, catheter-related VTE, and splanchnic thrombosis. If VTE event type was blank, it was included in the Other VTE. 95% CI was from the Agresti-Coull method.
Time frame: From first dose (Day 1) up to 114 days
Population: The Full Analysis Set contains all randomized participants and also those assigned to apixaban post-protocol amendment 8.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving Apixaban | Percentage of Participants With Other Symptomatic and Asymptomatic Venous Thromboembolism (VTE) | 1.9 percentage of participants |
| Participants Treated With Standard of Care | Percentage of Participants With Other Symptomatic and Asymptomatic Venous Thromboembolism (VTE) | 1.4 percentage of participants |
Secondary
Percentage of Participants With Stroke
Participants were assessed for incidence of stroke.
Time frame: From first dose (Day 1) up to 114 days
Population: The Full Analysis Set contains all randomized participants and also those assigned to apixaban post-PA8.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving Apixaban | Percentage of Participants With Stroke | 0 percentage of participants |
| Participants Treated With Standard of Care | Percentage of Participants With Stroke | 0 percentage of participants |
Secondary
Percentage of Participants With Symptomatic and Asymptomatic Recurrent Venous Thromboembolism (VTE)
Recurrent VTE, defined as either contiguous progression or non-contiguous new thrombus and including, but not limited to deep vein thrombosis (DVT), pulmonary embolism (PE) and paradoxical embolism. 95% CI was from the Agresti-Coull method.
Time frame: From first dose (Day 1) up to 114 days
Population: The Full Analysis Set contains all randomized participants and also those assigned to apixaban post-protocol amendment 8.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving Apixaban | Percentage of Participants With Symptomatic and Asymptomatic Recurrent Venous Thromboembolism (VTE) | 2.6 percentage of participants |
| Participants Treated With Standard of Care | Percentage of Participants With Symptomatic and Asymptomatic Recurrent Venous Thromboembolism (VTE) | 2.7 percentage of participants |
Secondary
Percentage of Participants With Venous Thromboembolism (VTE)-Related Mortality
Participants were assessed for death due to Venous Thromboembolism (VTE).
Time frame: From first dose (Day 1) up to 114 days
Population: The Full Analysis Set contains all randomized participants and also those assigned to apixaban post-PA8.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving Apixaban | Percentage of Participants With Venous Thromboembolism (VTE)-Related Mortality | 0 percentage of participants |
| Participants Treated With Standard of Care | Percentage of Participants With Venous Thromboembolism (VTE)-Related Mortality | 0 percentage of participants |