Trial Outcomes & Findings for Apixaban for the Acute Treatment of Venous Thromboembolism in Children (NCT NCT02464969)

Last Updated: 2024-10-29

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

229 participants

Primary outcome timeframe

From first dose (Day 1) up to 114 days

Results posted on

2024-10-29

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.
Main Phase (Day 1 to Day 84) STARTED	155	74
Main Phase (Day 1 to Day 84) COMPLETED	138	65
Main Phase (Day 1 to Day 84) NOT COMPLETED	17	9
Extension Phase (Day 85 to Day 168) STARTED	53	0
Extension Phase (Day 85 to Day 168) COMPLETED	50	0
Extension Phase (Day 85 to Day 168) NOT COMPLETED	3	0

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
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) Lost to Follow-up	3	0
Main Phase (Day 1 to Day 84) Withdrawal by Parent/Guardian	0	4
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) Entrance Criteria	1	1
Main Phase (Day 1 to Day 84) Withdrawal by Subject	1	0
Extension Phase (Day 85 to Day 168) Adverse Event	1	0
Extension Phase (Day 85 to Day 168) Withdrawal by Parent/Guardian	1	0
Extension Phase (Day 85 to Day 168) Other Reasons	1	0

Baseline Characteristics

Apixaban for the Acute Treatment of Venous Thromboembolism in Children

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Participants Receiving Apixaban n=155 Participants 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.	Participants Treated With Standard of Care n=74 Participants 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.	Total n=229 Participants Total of all reporting groups
Age, Continuous	11.10 years STANDARD_DEVIATION 6.51 • n=5 Participants	11.68 years STANDARD_DEVIATION 6.02 • n=7 Participants	11.29 years STANDARD_DEVIATION 6.35 • n=5 Participants
Sex: Female, Male Female	85 Participants n=5 Participants	43 Participants n=7 Participants	128 Participants n=5 Participants
Sex: Female, Male Male	70 Participants n=5 Participants	31 Participants n=7 Participants	101 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=5 Participants	13 Participants n=7 Participants	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	143 Participants n=5 Participants	61 Participants n=7 Participants	204 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	120 Participants n=5 Participants	55 Participants n=7 Participants	175 Participants n=5 Participants
Race/Ethnicity, Customized Black	22 Participants n=5 Participants	9 Participants n=7 Participants	31 Participants n=5 Participants
Race/Ethnicity, Customized Asian	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Multiracial	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Participants Receiving Apixaban n=152 Participants 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.	Participants Treated With Standard of Care n=73 Participants 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.	Participants With Age 28 Days - < 2 Years Participants with age 28 days - \< 2 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.	Participants in Age Group-Birth - ≤ 27 Days Participants in age group-Birth - ≤ 27 days 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;PK cohort neonates ≥ 2.6kg received 0.1mg BID. Dose was adjusted as determined by PK measurements (ie, 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.
Percentage of Participants With Composite of Major and Clinically Relevant Non-Major (CRNM) Bleeding	1.3 percentage of participants Interval 0.1 to 5.0	1.4 percentage of participants Interval 0.0 to 8.1	—	—

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Participants Receiving Apixaban n=155 Participants 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.	Participants Treated With Standard of Care n=74 Participants 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.	Participants With Age 28 Days - < 2 Years Participants with age 28 days - \< 2 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.	Participants in Age Group-Birth - ≤ 27 Days Participants in age group-Birth - ≤ 27 days 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;PK cohort neonates ≥ 2.6kg received 0.1mg BID. Dose was adjusted as determined by PK measurements (ie, 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.
Percentage of Participants With Symptomatic and Asymptomatic Recurrent Venous Thromboembolism (VTE) and VTE-Related Mortality	2.6 percentage of participants Interval 0.8 to 6.7	2.7 percentage of participants Interval 0.2 to 9.9	—	—

SECONDARY outcome

Timeframe: 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.

Death due to any cause was assessed. 95% CI was calculated using the Agresti-Coull method.

Outcome measures

Outcome measures
Measure	Participants Receiving Apixaban n=155 Participants 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.	Participants Treated With Standard of Care n=74 Participants 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.	Participants With Age 28 Days - < 2 Years Participants with age 28 days - \< 2 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.	Participants in Age Group-Birth - ≤ 27 Days Participants in age group-Birth - ≤ 27 days 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;PK cohort neonates ≥ 2.6kg received 0.1mg BID. Dose was adjusted as determined by PK measurements (ie, 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.
Percentage of Participants Who Died	1.3 percentage of participants Interval 0.1 to 4.9	1.4 percentage of participants Interval 0.0 to 8.0	—	—

SECONDARY outcome

Timeframe: 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.

Participants were assessed for death due to Venous Thromboembolism (VTE).

Outcome measures

Outcome measures
Measure	Participants Receiving Apixaban n=155 Participants 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.	Participants Treated With Standard of Care n=74 Participants 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.	Participants With Age 28 Days - < 2 Years Participants with age 28 days - \< 2 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.	Participants in Age Group-Birth - ≤ 27 Days Participants in age group-Birth - ≤ 27 days 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;PK cohort neonates ≥ 2.6kg received 0.1mg BID. Dose was adjusted as determined by PK measurements (ie, 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.
Percentage of Participants With Venous Thromboembolism (VTE)-Related Mortality	0 percentage of participants	0 percentage of participants	—	—

SECONDARY outcome

Timeframe: 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

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)

Outcome measures

Outcome measures
Measure	Participants Receiving Apixaban n=128 Participants 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.	Participants Treated With Standard of Care n=65 Participants 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.	Participants With Age 28 Days - < 2 Years Participants with age 28 days - \< 2 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.	Participants in Age Group-Birth - ≤ 27 Days Participants in age group-Birth - ≤ 27 days 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;PK cohort neonates ≥ 2.6kg received 0.1mg BID. Dose was adjusted as determined by PK measurements (ie, 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.
Number of Participants With Index Venous Thromboembolism (VTE) Status Recurrence-new	0 Participants	0 Participants	—	—
Number of Participants With Index Venous Thromboembolism (VTE) Status Recurrence-contiguous	2 Participants	0 Participants	—	—
Number of Participants With Index Venous Thromboembolism (VTE) Status Unchanged	8 Participants	6 Participants	—	—
Number of Participants With Index Venous Thromboembolism (VTE) Status Regression	25 Participants	11 Participants	—	—
Number of Participants With Index Venous Thromboembolism (VTE) Status Resolution	77 Participants	36 Participants	—	—
Number of Participants With Index Venous Thromboembolism (VTE) Status Indeterminate/Nondiagnostic	15 Participants	7 Participants	—	—
Number of Participants With Index Venous Thromboembolism (VTE) Status Missing Follow-up Imaging, therefore cannot compare to baseline	5 Participants	8 Participants	—	—
Number of Participants With Index Venous Thromboembolism (VTE) Status Imaging not completed within the specified time period	6 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Participants were assessed for incidence of stroke.

Outcome measures

Outcome measures
Measure	Participants Receiving Apixaban n=155 Participants 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.	Participants Treated With Standard of Care n=74 Participants 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.	Participants With Age 28 Days - < 2 Years Participants with age 28 days - \< 2 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.	Participants in Age Group-Birth - ≤ 27 Days Participants in age group-Birth - ≤ 27 days 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;PK cohort neonates ≥ 2.6kg received 0.1mg BID. Dose was adjusted as determined by PK measurements (ie, 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.
Percentage of Participants With Stroke	0 percentage of participants	0 percentage of participants	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Participants Receiving Apixaban n=155 Participants 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.	Participants Treated With Standard of Care n=74 Participants 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.	Participants With Age 28 Days - < 2 Years Participants with age 28 days - \< 2 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.	Participants in Age Group-Birth - ≤ 27 Days Participants in age group-Birth - ≤ 27 days 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;PK cohort neonates ≥ 2.6kg received 0.1mg BID. Dose was adjusted as determined by PK measurements (ie, 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.
Percentage of Participants With Symptomatic and Asymptomatic Recurrent Venous Thromboembolism (VTE)	2.6 percentage of participants Interval 0.8 to 6.7	2.7 percentage of participants Interval 0.2 to 9.9	—	—

SECONDARY outcome

Timeframe: 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.

Participants were assessed for incidence of Symptomatic or Asymptomatic Deep Vein Thrombosis (DVT) and New Symptomatic or Asymptomatic Pulmonary Embolism (PE).

Outcome measures

Outcome measures
Measure	Participants Receiving Apixaban n=155 Participants 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.	Participants Treated With Standard of Care n=74 Participants 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.	Participants With Age 28 Days - < 2 Years Participants with age 28 days - \< 2 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.	Participants in Age Group-Birth - ≤ 27 Days Participants in age group-Birth - ≤ 27 days 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;PK cohort neonates ≥ 2.6kg received 0.1mg BID. Dose was adjusted as determined by PK measurements (ie, 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.
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	1 Participants	—	—
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	0 Participants	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Participants Receiving Apixaban n=155 Participants 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.	Participants Treated With Standard of Care n=74 Participants 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.	Participants With Age 28 Days - < 2 Years Participants with age 28 days - \< 2 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.	Participants in Age Group-Birth - ≤ 27 Days Participants in age group-Birth - ≤ 27 days 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;PK cohort neonates ≥ 2.6kg received 0.1mg BID. Dose was adjusted as determined by PK measurements (ie, 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.
Percentage of Participants With Other Symptomatic and Asymptomatic Venous Thromboembolism (VTE)	1.9 percentage of participants Interval 0.4 to 5.8	1.4 percentage of participants Interval 0.0 to 8.0	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Participants Receiving Apixaban n=152 Participants 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.	Participants Treated With Standard of Care n=73 Participants 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.	Participants With Age 28 Days - < 2 Years Participants with age 28 days - \< 2 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.	Participants in Age Group-Birth - ≤ 27 Days Participants in age group-Birth - ≤ 27 days 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;PK cohort neonates ≥ 2.6kg received 0.1mg BID. Dose was adjusted as determined by PK measurements (ie, 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.
Number of Participants With Clinically Relevant Non-Major (CRNM) Bleeding, Major Bleeding and Minor Bleeding Major Bleeding	0 Participants	0 Participants	—	—
Number of Participants With Clinically Relevant Non-Major (CRNM) Bleeding, Major Bleeding and Minor Bleeding Clinically Relevant Non-major Bleeding	2 Participants	1 Participants	—	—
Number of Participants With Clinically Relevant Non-Major (CRNM) Bleeding, Major Bleeding and Minor Bleeding Minor Bleeding	54 Participants	21 Participants	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Participants Receiving Apixaban n=64 Participants 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.	Participants Treated With Standard of Care n=22 Participants 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.	Participants With Age 28 Days - < 2 Years n=15 Participants Participants with age 28 days - \< 2 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.	Participants in Age Group-Birth - ≤ 27 Days n=11 Participants Participants in age group-Birth - ≤ 27 days 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;PK cohort neonates ≥ 2.6kg received 0.1mg BID. Dose was adjusted as determined by PK measurements (ie, 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.
Blood Concentration of Apixaban (ng/mL) Hour 3 at Day 1	—	—	—	30.7 nanogram per millilitre (ng/mL) Standard Deviation 12.9
Blood Concentration of Apixaban (ng/mL) Hour 12 at Day 1	—	—	—	13.9 nanogram per millilitre (ng/mL) Standard Deviation 5.70
Blood Concentration of Apixaban (ng/mL) Hour 24 at Day 1	—	—	—	23.3 nanogram per millilitre (ng/mL) Standard Deviation 10.1
Blood Concentration of Apixaban (ng/mL) Pre-dose at Day 14	61.1 nanogram per millilitre (ng/mL) Standard Deviation 53.7	72.7 nanogram per millilitre (ng/mL) Standard Deviation 42.5	56.4 nanogram per millilitre (ng/mL) Standard Deviation 65.6	48.3 nanogram per millilitre (ng/mL) Standard Deviation 23.0
Blood Concentration of Apixaban (ng/mL) Post-dose at Day 14	152 nanogram per millilitre (ng/mL) Standard Deviation 80.2	189 nanogram per millilitre (ng/mL) Standard Deviation 61.0	203 nanogram per millilitre (ng/mL) Standard Deviation 118	119 nanogram per millilitre (ng/mL) Standard Deviation 45.7
Blood Concentration of Apixaban (ng/mL) Pre-dose at Day 42	54.5 nanogram per millilitre (ng/mL) Standard Deviation 33.7	67.9 nanogram per millilitre (ng/mL) Standard Deviation 33.8	123 nanogram per millilitre (ng/mL) Standard Deviation 123	50.2 nanogram per millilitre (ng/mL) Standard Deviation 34.1
Blood Concentration of Apixaban (ng/mL) Post-Dose at Day 42	151 nanogram per millilitre (ng/mL) Standard Deviation 79.1	212 nanogram per millilitre (ng/mL) Standard Deviation 89.8	143 nanogram per millilitre (ng/mL) Standard Deviation 88.0	109 nanogram per millilitre (ng/mL) Standard Deviation 56.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Participants Receiving Apixaban n=60 Participants 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.	Participants Treated With Standard of Care n=20 Participants 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.	Participants With Age 28 Days - < 2 Years n=13 Participants Participants with age 28 days - \< 2 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.	Participants in Age Group-Birth - ≤ 27 Days n=3 Participants Participants in age group-Birth - ≤ 27 days 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;PK cohort neonates ≥ 2.6kg received 0.1mg BID. Dose was adjusted as determined by PK measurements (ie, 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.
Concentration of Plasma Anti-Factor Xa (ng/mL) Pre-dose at Day 14	72.7 nanogram per millilitre (ng/mL) Standard Deviation 60.4	82.7 nanogram per millilitre (ng/mL) Standard Deviation 41.3	74.7 nanogram per millilitre (ng/mL) Standard Deviation 69.7	48.0 nanogram per millilitre (ng/mL) Standard Deviation 1.00
Concentration of Plasma Anti-Factor Xa (ng/mL) Post-dose at Day 14	147 nanogram per millilitre (ng/mL) Standard Deviation 83.5	202 nanogram per millilitre (ng/mL) Standard Deviation 75.8	190 nanogram per millilitre (ng/mL) Standard Deviation 105	127 nanogram per millilitre (ng/mL) Standard Deviation 4.04
Concentration of Plasma Anti-Factor Xa (ng/mL) Pre-dose at Day 42	63.9 nanogram per millilitre (ng/mL) Standard Deviation 27.4	75.3 nanogram per millilitre (ng/mL) Standard Deviation 31.0	53.5 nanogram per millilitre (ng/mL) Standard Deviation 13.4	—
Concentration of Plasma Anti-Factor Xa (ng/mL) Post-Dose at Day 42	153 nanogram per millilitre (ng/mL) Standard Deviation 84.9	220 nanogram per millilitre (ng/mL) Standard Deviation 98.4	156 nanogram per millilitre (ng/mL) Standard Deviation 92.2	101 nanogram per millilitre (ng/mL) Standard Deviation NA Only 1 participant was analyzed hence SD not applicable

Adverse Events

Participants Receiving Apixaban

Serious events: 40 serious events

Other events: 132 other events

Deaths: 2 deaths

Participants Treated With Standard of Care

Serious events: 17 serious events

Other events: 59 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER