Trial Outcomes & Findings for A Study of the Safety and Pharmacokinetics of Apixaban Versus Vitamin K Antagonist (VKA) or Low Molecular Weight Heparin (LMWH) in Pediatric Subjects With Congenital or Acquired Heart Disease Requiring Anticoagulation (NCT NCT02981472)

Last Updated: 2022-10-03

Results Overview

The number of participants with adjudicated major or CRNM bleeding events per the Perinatal and Paediatric Haemostasis Subcommittee of International Society on Thrombosis and Haemostasis (ISTH) criteria. Events are adjudicated by a blinded, independent events adjudication committee (EAC). Major bleeding satisfies one or more of the following criteria: fatal bleeding, clinically overt bleeding associated with a decrease in hemoglobin of at least 20 g/L (i.e., 2 g/dL) in a 24-hour period, bleeding that is retroperitoneal, pulmonary, intracranial, or otherwise involves the CNS, or bleeding that requires surgical intervention in an operating suite, including interventional radiology. CRNM bleeding satisfies one or both of the following criteria: overt bleeding for which blood product is administered and not directly attributable to the subject's underlying medical condition or bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating room.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

192 participants

Primary outcome timeframe

From first dose to 2 days after last dose (Up to approximately 12 months)

Results posted on

2022-10-03

Participant Flow

192 participants were randomized and 188 received treatment

Participant milestones

Participant milestones
Measure	Apixaban Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between \>/= 3 and \< 35 kg will be administered apixaban twice daily (BID) in doses between 0.2mg and 4 mg depending on body weight. Children randomized to the apixaban arm of the study weighing \>/= 35 kg will be administered apixaban 5 mg twice daily (BID).	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA) Participants receive thromboprophylaxis with VKA or LMWH for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants who receive LMWH are allowed to switch to VKA at any time during the study; conversely, Participants having difficulty with VKA may switch to LMWH.
Pre-Treatment Period STARTED	129	63
Pre-Treatment Period COMPLETED	126	62
Pre-Treatment Period NOT COMPLETED	3	1
Treatment Period STARTED	126	62
Treatment Period COMPLETED	119	60
Treatment Period NOT COMPLETED	7	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Apixaban Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between \>/= 3 and \< 35 kg will be administered apixaban twice daily (BID) in doses between 0.2mg and 4 mg depending on body weight. Children randomized to the apixaban arm of the study weighing \>/= 35 kg will be administered apixaban 5 mg twice daily (BID).	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA) Participants receive thromboprophylaxis with VKA or LMWH for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants who receive LMWH are allowed to switch to VKA at any time during the study; conversely, Participants having difficulty with VKA may switch to LMWH.
Pre-Treatment Period Participant withdrew consent	2	1
Pre-Treatment Period Participant no longer meets study criteria	1	0
Treatment Period Adverse Event	6	1
Treatment Period Participant withdrew consent	1	0
Treatment Period Lost to Follow-up	0	1

Baseline Characteristics

A Study of the Safety and Pharmacokinetics of Apixaban Versus Vitamin K Antagonist (VKA) or Low Molecular Weight Heparin (LMWH) in Pediatric Subjects With Congenital or Acquired Heart Disease Requiring Anticoagulation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Apixaban n=129 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between \>/= 3 and \< 35 kg will be administered apixaban twice daily (BID) in doses between 0.2mg and 4 mg depending on body weight. Children randomized to the apixaban arm of the study weighing \>/= 35 kg will be administered apixaban 5 mg twice daily (BID).	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA) n=63 Participants Participants receive thromboprophylaxis with VKA or LMWH for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants who receive LMWH are allowed to switch to VKA at any time during the study; conversely, Participants having difficulty with VKA may switch to LMWH.	Total n=192 Participants Total of all reporting groups
Age, Continuous	7.96 Years STANDARD_DEVIATION 4.553 • n=99 Participants	7.56 Years STANDARD_DEVIATION 4.408 • n=107 Participants	7.83 Years STANDARD_DEVIATION 4.499 • n=206 Participants
Age, Customized 28 DAYS - < 2 YEARS	8 Participants n=99 Participants	3 Participants n=107 Participants	11 Participants n=206 Participants
Age, Customized 2 YEARS - < 6 YEARS	40 Participants n=99 Participants	22 Participants n=107 Participants	62 Participants n=206 Participants
Age, Customized 6 YEARS - < 12 YEARS	49 Participants n=99 Participants	23 Participants n=107 Participants	72 Participants n=206 Participants
Age, Customized 12 YEARS - < 18 YEARS	32 Participants n=99 Participants	15 Participants n=107 Participants	47 Participants n=206 Participants
Sex: Female, Male Female	67 Participants n=99 Participants	23 Participants n=107 Participants	90 Participants n=206 Participants
Sex: Female, Male Male	62 Participants n=99 Participants	40 Participants n=107 Participants	102 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	20 Participants n=99 Participants	14 Participants n=107 Participants	34 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	105 Participants n=99 Participants	47 Participants n=107 Participants	152 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=99 Participants	2 Participants n=107 Participants	6 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Asian	6 Participants n=99 Participants	4 Participants n=107 Participants	10 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	7 Participants n=99 Participants	2 Participants n=107 Participants	9 Participants n=206 Participants
Race (NIH/OMB) White	109 Participants n=99 Participants	51 Participants n=107 Participants	160 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=99 Participants	6 Participants n=107 Participants	12 Participants n=206 Participants

PRIMARY outcome

Timeframe: From first dose to 2 days after last dose (Up to approximately 12 months)

Population: All treated participants

Outcome measures

Outcome measures
Measure	Apixaban n=126 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between \>/= 3 and \< 35 kg will be administered apixaban twice daily (BID) in doses between 0.2mg and 4 mg depending on body weight. Children randomized to the apixaban arm of the study weighing \>/= 35 kg will be administered apixaban 5 mg twice daily (BID).	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA) n=62 Participants Participants receive thromboprophylaxis with VKA or LMWH for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants who receive LMWH are allowed to switch to VKA at any time during the study; conversely, Participants having difficulty with VKA may switch to LMWH.	Participants Weight Range 12 to < 18 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 12 to \< 18 kg will be administered 2mg apixaban twice daily (BID).	Participants Weight Range 18 to < 25 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 18 to \< 25 kg will be administered 3mg apixaban twice daily (BID).	Participants Weight Range 25 to < 35 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 25 to \< 35 kg will be administered 4mg apixaban twice daily (BID).	Participants Weight Range ≥ 35 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between ≥ 35 kg will be administered 5mg apixaban twice daily (BID).
Composite of Adjudicated Major or Clinically Relevant Non-Major (CRNM) Bleeding Events	1 Participants	3 Participants	—	—	—	—

SECONDARY outcome

Timeframe: From randomization to 2 days after last dose (Up to approximately 12 months)

Population: All randomized participants

The number of participants with thromboembolic events (intra-cardiac, shunt, inside Fontan pathway, pulmonary embolism (PE), stroke, other arterial or venous thromboembolic events, etc.) and thromboembolic event-related death detected by imaging or clinical diagnosis. Death and thromboembolic events are adjudicated by a blinded, independent events adjudication committee (EAC)

Outcome measures

Outcome measures
Measure	Apixaban n=129 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between \>/= 3 and \< 35 kg will be administered apixaban twice daily (BID) in doses between 0.2mg and 4 mg depending on body weight. Children randomized to the apixaban arm of the study weighing \>/= 35 kg will be administered apixaban 5 mg twice daily (BID).	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA) n=63 Participants Participants receive thromboprophylaxis with VKA or LMWH for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants who receive LMWH are allowed to switch to VKA at any time during the study; conversely, Participants having difficulty with VKA may switch to LMWH.	Participants Weight Range 12 to < 18 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 12 to \< 18 kg will be administered 2mg apixaban twice daily (BID).	Participants Weight Range 18 to < 25 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 18 to \< 25 kg will be administered 3mg apixaban twice daily (BID).	Participants Weight Range 25 to < 35 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 25 to \< 35 kg will be administered 4mg apixaban twice daily (BID).	Participants Weight Range ≥ 35 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between ≥ 35 kg will be administered 5mg apixaban twice daily (BID).
The Number of Participants With Thrombotic Events and Thromboembolic Event-Related Death Thromboembolic event	0 Participants	0 Participants	—	—	—	—
The Number of Participants With Thrombotic Events and Thromboembolic Event-Related Death Thromboembolic event-related death	0 Participants	0 Participants	—	—	—	—

SECONDARY outcome

Timeframe: From first dose to 2 days after last dose (Up to approximately 12 months)

Population: All treated participants

The number of participants with adjudicated major bleeding events per the Perinatal and Paediatric Haemostasis Subcommittee of International Society on Thrombosis and Haemostasis (ISTH) criteria. Major bleeding events are adjudicated by a blinded, independent events adjudication committee (EAC). Major bleeding is defined as bleeding that satisfies one or more of the following criteria: * fatal bleeding * clinically overt bleeding associated with a decrease in hemoglobin of at least 20 g/L (i.e., 2 g/dL) in a 24-hour period * bleeding that is retroperitoneal, pulmonary, intracranial, or otherwise involves the CNS * bleeding that requires surgical intervention in an operating suite, including interventional radiology

Outcome measures

Outcome measures
Measure	Apixaban n=126 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between \>/= 3 and \< 35 kg will be administered apixaban twice daily (BID) in doses between 0.2mg and 4 mg depending on body weight. Children randomized to the apixaban arm of the study weighing \>/= 35 kg will be administered apixaban 5 mg twice daily (BID).	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA) n=62 Participants Participants receive thromboprophylaxis with VKA or LMWH for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants who receive LMWH are allowed to switch to VKA at any time during the study; conversely, Participants having difficulty with VKA may switch to LMWH.	Participants Weight Range 12 to < 18 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 12 to \< 18 kg will be administered 2mg apixaban twice daily (BID).	Participants Weight Range 18 to < 25 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 18 to \< 25 kg will be administered 3mg apixaban twice daily (BID).	Participants Weight Range 25 to < 35 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 25 to \< 35 kg will be administered 4mg apixaban twice daily (BID).	Participants Weight Range ≥ 35 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between ≥ 35 kg will be administered 5mg apixaban twice daily (BID).
The Number of Participants With Adjudicated Major Bleeding	1 Participants	1 Participants	—	—	—	—

SECONDARY outcome

Timeframe: From first dose to 2 days after last dose (Up to approximately 12 months)

Population: All treated participants

The number of participants with adjudicated clinically relevant non-major (CRNM) bleeding events per the Perinatal and Paediatric Haemostasis Subcommittee of International Society on Thrombosis and Haemostasis (ISTH) criteria. CRNM bleeding events are adjudicated by a blinded, independent events adjudication committee (EAC). CRNM bleeding is defined as bleeding that satisfies one or both of the following criteria: * overt bleeding for which blood product is administered and not directly attributable to the subject's underlying medical condition * bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating room

Outcome measures

Outcome measures
Measure	Apixaban n=126 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between \>/= 3 and \< 35 kg will be administered apixaban twice daily (BID) in doses between 0.2mg and 4 mg depending on body weight. Children randomized to the apixaban arm of the study weighing \>/= 35 kg will be administered apixaban 5 mg twice daily (BID).	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA) n=62 Participants Participants receive thromboprophylaxis with VKA or LMWH for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants who receive LMWH are allowed to switch to VKA at any time during the study; conversely, Participants having difficulty with VKA may switch to LMWH.	Participants Weight Range 12 to < 18 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 12 to \< 18 kg will be administered 2mg apixaban twice daily (BID).	Participants Weight Range 18 to < 25 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 18 to \< 25 kg will be administered 3mg apixaban twice daily (BID).	Participants Weight Range 25 to < 35 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 25 to \< 35 kg will be administered 4mg apixaban twice daily (BID).	Participants Weight Range ≥ 35 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between ≥ 35 kg will be administered 5mg apixaban twice daily (BID).
The Number of Participants With Adjudicated CRNM Bleeding	1 Participants	2 Participants	—	—	—	—

SECONDARY outcome

Timeframe: From first dose to 2 days after last dose (Up to approximately 12 months)

Population: All treated participants

The number of participants with all adjudicated bleeding events

Outcome measures

Outcome measures
Measure	Apixaban n=126 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between \>/= 3 and \< 35 kg will be administered apixaban twice daily (BID) in doses between 0.2mg and 4 mg depending on body weight. Children randomized to the apixaban arm of the study weighing \>/= 35 kg will be administered apixaban 5 mg twice daily (BID).	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA) n=62 Participants Participants receive thromboprophylaxis with VKA or LMWH for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants who receive LMWH are allowed to switch to VKA at any time during the study; conversely, Participants having difficulty with VKA may switch to LMWH.	Participants Weight Range 12 to < 18 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 12 to \< 18 kg will be administered 2mg apixaban twice daily (BID).	Participants Weight Range 18 to < 25 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 18 to \< 25 kg will be administered 3mg apixaban twice daily (BID).	Participants Weight Range 25 to < 35 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 25 to \< 35 kg will be administered 4mg apixaban twice daily (BID).	Participants Weight Range ≥ 35 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between ≥ 35 kg will be administered 5mg apixaban twice daily (BID).
The Number of Participants With All Adjudicated Bleeding	47 Participants	23 Participants	—	—	—	—

SECONDARY outcome

Timeframe: From first dose to 2 days after last dose (Up to approximately 12 months)

Population: All treated participants

The number of participants with drug discontinuation due to adverse effects, intolerability, or bleeding.

Outcome measures

Outcome measures
Measure	Apixaban n=126 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between \>/= 3 and \< 35 kg will be administered apixaban twice daily (BID) in doses between 0.2mg and 4 mg depending on body weight. Children randomized to the apixaban arm of the study weighing \>/= 35 kg will be administered apixaban 5 mg twice daily (BID).	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA) n=62 Participants Participants receive thromboprophylaxis with VKA or LMWH for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants who receive LMWH are allowed to switch to VKA at any time during the study; conversely, Participants having difficulty with VKA may switch to LMWH.	Participants Weight Range 12 to < 18 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 12 to \< 18 kg will be administered 2mg apixaban twice daily (BID).	Participants Weight Range 18 to < 25 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 18 to \< 25 kg will be administered 3mg apixaban twice daily (BID).	Participants Weight Range 25 to < 35 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 25 to \< 35 kg will be administered 4mg apixaban twice daily (BID).	Participants Weight Range ≥ 35 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between ≥ 35 kg will be administered 5mg apixaban twice daily (BID).
The Number of Participants With Drug Discontinuation Due to Adverse Effects, Intolerability, or Bleeding	7 Participants	1 Participants	—	—	—	—

SECONDARY outcome

Timeframe: From first dose to 2 days after last dose (Up to approximately 12 months)

Population: All treated participants

The number of participant deaths in the study.

Outcome measures

Outcome measures
Measure	Apixaban n=126 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between \>/= 3 and \< 35 kg will be administered apixaban twice daily (BID) in doses between 0.2mg and 4 mg depending on body weight. Children randomized to the apixaban arm of the study weighing \>/= 35 kg will be administered apixaban 5 mg twice daily (BID).	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA) n=62 Participants Participants receive thromboprophylaxis with VKA or LMWH for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants who receive LMWH are allowed to switch to VKA at any time during the study; conversely, Participants having difficulty with VKA may switch to LMWH.	Participants Weight Range 12 to < 18 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 12 to \< 18 kg will be administered 2mg apixaban twice daily (BID).	Participants Weight Range 18 to < 25 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 18 to \< 25 kg will be administered 3mg apixaban twice daily (BID).	Participants Weight Range 25 to < 35 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 25 to \< 35 kg will be administered 4mg apixaban twice daily (BID).	Participants Weight Range ≥ 35 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between ≥ 35 kg will be administered 5mg apixaban twice daily (BID).
The Number of Participant Deaths in the Study	0 Participants	0 Participants	—	—	—	—

SECONDARY outcome

Timeframe: From first dose up to 6 months after first dose

Population: All treated participants in the apixaban arm with available pharmacokinetic data

Outcome measures

Outcome measures
Measure	Apixaban n=6 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between \>/= 3 and \< 35 kg will be administered apixaban twice daily (BID) in doses between 0.2mg and 4 mg depending on body weight. Children randomized to the apixaban arm of the study weighing \>/= 35 kg will be administered apixaban 5 mg twice daily (BID).	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA) n=2 Participants Participants receive thromboprophylaxis with VKA or LMWH for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants who receive LMWH are allowed to switch to VKA at any time during the study; conversely, Participants having difficulty with VKA may switch to LMWH.	Participants Weight Range 12 to < 18 kg n=28 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 12 to \< 18 kg will be administered 2mg apixaban twice daily (BID).	Participants Weight Range 18 to < 25 kg n=29 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 18 to \< 25 kg will be administered 3mg apixaban twice daily (BID).	Participants Weight Range 25 to < 35 kg n=24 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 25 to \< 35 kg will be administered 4mg apixaban twice daily (BID).	Participants Weight Range ≥ 35 kg n=35 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between ≥ 35 kg will be administered 5mg apixaban twice daily (BID).
Maximum Observed Concentration (Cmax)	185 ng/mL Geometric Coefficient of Variation 48.8	218 ng/mL Geometric Coefficient of Variation 23.4	222 ng/mL Geometric Coefficient of Variation 39.6	244 ng/mL Geometric Coefficient of Variation 30.7	249 ng/mL Geometric Coefficient of Variation 37.7	203 ng/mL Geometric Coefficient of Variation 35.9

SECONDARY outcome

Timeframe: From first dose up to 6 months after first dose

Population: All treated participants in the apixaban arm with available pharmacokinetic data

Outcome measures

Outcome measures
Measure	Apixaban n=6 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between \>/= 3 and \< 35 kg will be administered apixaban twice daily (BID) in doses between 0.2mg and 4 mg depending on body weight. Children randomized to the apixaban arm of the study weighing \>/= 35 kg will be administered apixaban 5 mg twice daily (BID).	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA) n=2 Participants Participants receive thromboprophylaxis with VKA or LMWH for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants who receive LMWH are allowed to switch to VKA at any time during the study; conversely, Participants having difficulty with VKA may switch to LMWH.	Participants Weight Range 12 to < 18 kg n=28 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 12 to \< 18 kg will be administered 2mg apixaban twice daily (BID).	Participants Weight Range 18 to < 25 kg n=29 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 18 to \< 25 kg will be administered 3mg apixaban twice daily (BID).	Participants Weight Range 25 to < 35 kg n=24 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 25 to \< 35 kg will be administered 4mg apixaban twice daily (BID).	Participants Weight Range ≥ 35 kg n=35 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between ≥ 35 kg will be administered 5mg apixaban twice daily (BID).
Trough Observed Concentration (Cmin)	57.9 ng/mL Geometric Coefficient of Variation 90.3	82.7 ng/mL Geometric Coefficient of Variation 21.5	64.3 ng/mL Geometric Coefficient of Variation 69.5	67.4 ng/mL Geometric Coefficient of Variation 58.9	73.1 ng/mL Geometric Coefficient of Variation 64.7	72.7 ng/mL Geometric Coefficient of Variation 46.8

SECONDARY outcome

Timeframe: From first dose up to 6 months after first dose

Population: All treated participants in the apixaban arm with available pharmacokinetic data

Outcome measures

Outcome measures
Measure	Apixaban n=6 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between \>/= 3 and \< 35 kg will be administered apixaban twice daily (BID) in doses between 0.2mg and 4 mg depending on body weight. Children randomized to the apixaban arm of the study weighing \>/= 35 kg will be administered apixaban 5 mg twice daily (BID).	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA) n=2 Participants Participants receive thromboprophylaxis with VKA or LMWH for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants who receive LMWH are allowed to switch to VKA at any time during the study; conversely, Participants having difficulty with VKA may switch to LMWH.	Participants Weight Range 12 to < 18 kg n=28 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 12 to \< 18 kg will be administered 2mg apixaban twice daily (BID).	Participants Weight Range 18 to < 25 kg n=29 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 18 to \< 25 kg will be administered 3mg apixaban twice daily (BID).	Participants Weight Range 25 to < 35 kg n=24 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 25 to \< 35 kg will be administered 4mg apixaban twice daily (BID).	Participants Weight Range ≥ 35 kg n=35 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between ≥ 35 kg will be administered 5mg apixaban twice daily (BID).
Area Under the Concentration-Time Curve in One Dosing Interval (AUC (TAU))	1460 ng • h/mL Geometric Coefficient of Variation 61.2	1840 ng • h/mL Geometric Coefficient of Variation 20.7	1610 ng • h/mL Geometric Coefficient of Variation 49.6	1760 ng • h/mL Geometric Coefficient of Variation 38.3	1840 ng • h/mL Geometric Coefficient of Variation 43.3	1630 ng • h/mL Geometric Coefficient of Variation 37.3

SECONDARY outcome

Timeframe: From first dose up to 6 months after first dose

Population: All treated participants in the apixaban arm with available pharmacokinetic data

Outcome measures

Outcome measures
Measure	Apixaban n=6 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between \>/= 3 and \< 35 kg will be administered apixaban twice daily (BID) in doses between 0.2mg and 4 mg depending on body weight. Children randomized to the apixaban arm of the study weighing \>/= 35 kg will be administered apixaban 5 mg twice daily (BID).	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA) n=2 Participants Participants receive thromboprophylaxis with VKA or LMWH for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants who receive LMWH are allowed to switch to VKA at any time during the study; conversely, Participants having difficulty with VKA may switch to LMWH.	Participants Weight Range 12 to < 18 kg n=28 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 12 to \< 18 kg will be administered 2mg apixaban twice daily (BID).	Participants Weight Range 18 to < 25 kg n=29 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 18 to \< 25 kg will be administered 3mg apixaban twice daily (BID).	Participants Weight Range 25 to < 35 kg n=24 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 25 to \< 35 kg will be administered 4mg apixaban twice daily (BID).	Participants Weight Range ≥ 35 kg n=35 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between ≥ 35 kg will be administered 5mg apixaban twice daily (BID).
Time of Maximum Observed Concentration (Tmax)	2.24 hours Interval 1.41 to 2.83	2.47 hours Interval 2.23 to 2.71	1.72 hours Interval 0.938 to 3.35	1.74 hours Interval 0.775 to 2.18	1.65 hours Interval 1.26 to 2.85	1.85 hours Interval 1.47 to 2.93

SECONDARY outcome

Timeframe: From first dose up to 6 months after first dose

Population: All treated participants in the apixaban arm that have anti-FXa samples collected

Anti-FXa Activity was measured to assess participant plasma apixaban levels. 125 participants received at least one dose of apixaban and had anti-FXa samples collected that contributed measurements to at least one of the timepoints below.

Outcome measures

Outcome measures
Measure	Apixaban n=125 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between \>/= 3 and \< 35 kg will be administered apixaban twice daily (BID) in doses between 0.2mg and 4 mg depending on body weight. Children randomized to the apixaban arm of the study weighing \>/= 35 kg will be administered apixaban 5 mg twice daily (BID).	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA) Participants receive thromboprophylaxis with VKA or LMWH for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants who receive LMWH are allowed to switch to VKA at any time during the study; conversely, Participants having difficulty with VKA may switch to LMWH.	Participants Weight Range 12 to < 18 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 12 to \< 18 kg will be administered 2mg apixaban twice daily (BID).	Participants Weight Range 18 to < 25 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 18 to \< 25 kg will be administered 3mg apixaban twice daily (BID).	Participants Weight Range 25 to < 35 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 25 to \< 35 kg will be administered 4mg apixaban twice daily (BID).	Participants Weight Range ≥ 35 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between ≥ 35 kg will be administered 5mg apixaban twice daily (BID).
Anti-FXa Activity Day 1 (4 HRS POSTDOSE)	147.69 ng/mL Standard Error 7.243	—	—	—	—	—
Anti-FXa Activity Week 2 (PREDOSE)	86.24 ng/mL Standard Error 7.652	—	—	—	—	—
Anti-FXa Activity Week 2 (2 HRS POSTDOSE)	242.34 ng/mL Standard Error 18.966	—	—	—	—	—
Anti-FXa Activity Month 3 (2 HRS POSTDOSE)	228.88 ng/mL Standard Error 14.263	—	—	—	—	—
Anti-FXa Activity Month 6 (PREDOSE)	66.93 ng/mL Standard Error 6.532	—	—	—	—	—

SECONDARY outcome

Timeframe: From first dose up to 6 months after first dose

Population: All treated participants in the apixaban arm that have have chromogenic FX assay samples collected

Chromogenic FX was measured to assess (apparent) FX levels in participants and inhibition of FXa by apixaban. 125 participants received at least one dose of apixaban and had chromogenic FX assay samples collected that contributed measurements to at least one of the timepoints below.

Outcome measures

Outcome measures
Measure	Apixaban n=125 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between \>/= 3 and \< 35 kg will be administered apixaban twice daily (BID) in doses between 0.2mg and 4 mg depending on body weight. Children randomized to the apixaban arm of the study weighing \>/= 35 kg will be administered apixaban 5 mg twice daily (BID).	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA) Participants receive thromboprophylaxis with VKA or LMWH for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants who receive LMWH are allowed to switch to VKA at any time during the study; conversely, Participants having difficulty with VKA may switch to LMWH.	Participants Weight Range 12 to < 18 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 12 to \< 18 kg will be administered 2mg apixaban twice daily (BID).	Participants Weight Range 18 to < 25 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 18 to \< 25 kg will be administered 3mg apixaban twice daily (BID).	Participants Weight Range 25 to < 35 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 25 to \< 35 kg will be administered 4mg apixaban twice daily (BID).	Participants Weight Range ≥ 35 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between ≥ 35 kg will be administered 5mg apixaban twice daily (BID).
Chromogenic FX Assay (Apparent FX Level) Month 3 (2 HRS POSTDOSE)	18.25 Percent Standard Error 0.970	—	—	—	—	—
Chromogenic FX Assay (Apparent FX Level) Day 1 (PREDOSE)	58.87 Percent Standard Error 2.368	—	—	—	—	—
Chromogenic FX Assay (Apparent FX Level) Day 1 (4 HRS POSTDOSE)	18.90 Percent Standard Error 1.205	—	—	—	—	—
Chromogenic FX Assay (Apparent FX Level) Week 2 (PREDOSE)	35.88 Percent Standard Error 1.973	—	—	—	—	—
Chromogenic FX Assay (Apparent FX Level) Week 2 (2 HRS POSTDOSE)	21.26 Percent Standard Error 1.680	—	—	—	—	—
Chromogenic FX Assay (Apparent FX Level) Month 6 (PREDOSE)	36.57 Percent Standard Error 1.943	—	—	—	—	—

SECONDARY outcome

Timeframe: from randomization up to 12 months after randomization

Population: All randomized English speaking participants 2 years and older with both baseline and post baseline questionnaire scores

Subjects' quality of life was measured using the PedsQL instrument administered only to English-speaking children/parents. Only subjects who completed the questionnaires at both baseline and post-baseline visits were included in the analyses. PedsQL consists of 23 items scored on a 5-point Likert scale from 0 (never) to 4 (almost always) or for the child report for younger children ages 5-7, a 3-point Likert scale: 0 (Not at all), 2 (Sometimes), and 4 (A lot). Scores are reverse scored and transformed to a 0-100 scale as follows: 0=100, 1=75, 3=25, 4=0. Higher scores indicate a better HRQOL and/or lower problems.

Outcome measures

Outcome measures
Measure	Apixaban n=129 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between \>/= 3 and \< 35 kg will be administered apixaban twice daily (BID) in doses between 0.2mg and 4 mg depending on body weight. Children randomized to the apixaban arm of the study weighing \>/= 35 kg will be administered apixaban 5 mg twice daily (BID).	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA) n=63 Participants Participants receive thromboprophylaxis with VKA or LMWH for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants who receive LMWH are allowed to switch to VKA at any time during the study; conversely, Participants having difficulty with VKA may switch to LMWH.	Participants Weight Range 12 to < 18 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 12 to \< 18 kg will be administered 2mg apixaban twice daily (BID).	Participants Weight Range 18 to < 25 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 18 to \< 25 kg will be administered 3mg apixaban twice daily (BID).	Participants Weight Range 25 to < 35 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 25 to \< 35 kg will be administered 4mg apixaban twice daily (BID).	Participants Weight Range ≥ 35 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between ≥ 35 kg will be administered 5mg apixaban twice daily (BID).
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) TREATMENT II ASSESSED BY PARENT - MONTH 12	90.30 Score on a scale Standard Deviation 12.381	83.80 Score on a scale Standard Deviation 18.915	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) PERCEIVED PHYSICAL APPEARANCE ASSESSED BY PARENT - MONTH 12	79.38 Score on a scale Standard Deviation 21.012	74.33 Score on a scale Standard Deviation 26.998	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) TREATMENT ANXIETY ASSESSED BY PARENT - BASELINE	61.44 Score on a scale Standard Deviation 30.804	56.27 Score on a scale Standard Deviation 33.997	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) TREATMENT ANXIETY ASSESSED BY PARENT - MONTH 12	64.03 Score on a scale Standard Deviation 29.567	57.77 Score on a scale Standard Deviation 34.199	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) GENERAL-SPECIFIC MODULE ASSESSED BY CHILD - BASELINE	69.64 Score on a scale Standard Deviation 15.512	60.71 Score on a scale Standard Deviation 17.374	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) GENERAL-SPECIFIC MODULE ASSESSED BY CHILD - MONTH 12	73.37 Score on a scale Standard Deviation 19.998	64.81 Score on a scale Standard Deviation 22.327	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) GENERAL-SPECIFIC MODULE ASSESSED BY PARENT - BASELINE	65.61 Score on a scale Standard Deviation 16.625	65.42 Score on a scale Standard Deviation 18.000	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) GENERAL-SPECIFIC MODULE ASSESSED BY PARENT - MONTH 12	70.00 Score on a scale Standard Deviation 19.560	70.32 Score on a scale Standard Deviation 21.949	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) HEART PROBLEMS AND TREATMENT ASSESSED BY CHILD - BASELINE	65.34 Score on a scale Standard Deviation 22.130	64.70 Score on a scale Standard Deviation 18.465	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) HEART PROBLEMS AND TREATMENT ASSESSED BY CHILD - MONTH 12	69.46 Score on a scale Standard Deviation 21.119	63.44 Score on a scale Standard Deviation 19.836	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) TREATMENT II ASSESSED BY CHILD - BASELINE	87.39 Score on a scale Standard Deviation 22.994	85.68 Score on a scale Standard Deviation 15.857	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) TREATMENT II ASSESSED BY CHILD - MONTH 12	91.77 Score on a scale Standard Deviation 10.896	86.27 Score on a scale Standard Deviation 16.400	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) PERCEIVED PHYSICAL APPEARANCE ASSESSED BY CHILD - BASELINE	75.51 Score on a scale Standard Deviation 27.477	78.44 Score on a scale Standard Deviation 23.390	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) PERCEIVED PHYSICAL APPEARANCE ASSESSED BY CHILD - MONTH 12	80.56 Score on a scale Standard Deviation 22.408	81.37 Score on a scale Standard Deviation 30.689	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) TREATMENT ANXIETY ASSESSED BY CHILD - BASELINE	80.52 Score on a scale Standard Deviation 23.420	60.31 Score on a scale Standard Deviation 34.162	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) TREATMENT ANXIETY ASSESSED BY CHILD - MONTH 12	80.71 Score on a scale Standard Deviation 25.480	60.31 Score on a scale Standard Deviation 38.333	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) COGNITIVE PROBLEMS ASSESSED BY CHILD - BASELINE	69.85 Score on a scale Standard Deviation 20.871	53.24 Score on a scale Standard Deviation 20.382	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) COGNITIVE PROBLEMS ASSESSED BY CHILD - MONTH 12	68.24 Score on a scale Standard Deviation 24.367	53.53 Score on a scale Standard Deviation 26.796	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) COMMUNICATION ASSESSED BY CHILD - BASELINE	66.15 Score on a scale Standard Deviation 30.000	63.55 Score on a scale Standard Deviation 28.998	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) COMMUNICATION ASSESSED BY CHILD - MONTH 12	70.31 Score on a scale Standard Deviation 26.681	57.28 Score on a scale Standard Deviation 38.948	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) HEART PROBLEMS AND TREATMENT ASSESSED BY PARENT - BASELINE	63.68 Score on a scale Standard Deviation 20.727	67.71 Score on a scale Standard Deviation 22.668	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) HEART PROBLEMS AND TREATMENT ASSESSED BY PARENT - MONTH 12	66.37 Score on a scale Standard Deviation 20.811	69.00 Score on a scale Standard Deviation 23.688	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) TREATMENT II ASSESSED BY PARENT - BASELINE	91.41 Score on a scale Standard Deviation 11.557	85.27 Score on a scale Standard Deviation 17.325	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) PERCEIVED PHYSICAL APPEARANCE ASSESSED BY PARENT - BASELINE	79.16 Score on a scale Standard Deviation 22.571	79.66 Score on a scale Standard Deviation 22.958	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) COGNITIVE PROBLEMS ASSESSED BY PARENT - BASELINE	60.29 Score on a scale Standard Deviation 29.558	61.60 Score on a scale Standard Deviation 25.807	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) COGNITIVE PROBLEMS ASSESSED BY PARENT - MONTH 12	58.69 Score on a scale Standard Deviation 29.560	58.53 Score on a scale Standard Deviation 33.432	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) COMMUNICATION ASSESSED BY PARENT - BASELINE	65.57 Score on a scale Standard Deviation 27.342	67.33 Score on a scale Standard Deviation 28.257	—	—	—	—
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) COMMUNICATION ASSESSED BY PARENT - MONTH 12	68.20 Score on a scale Standard Deviation 24.037	66.17 Score on a scale Standard Deviation 28.067	—	—	—	—

SECONDARY outcome

Timeframe: from randomization up to 12 months after randomization

Population: All randomized English speaking participants 6 years and older taking apixaban or warfarin with both baseline and post baseline questionnaire scores. Parent inventory includes only participants age \>= 34 weeks old.

Subjects' quality of life was measured using the KIDCLOT instrument administered only to English-speaking children/parents. Only subjects who completed the questionnaires at both baseline and post-baseline visits were included in the analyses. KIDCLOT Parent inventory uses a 5 point Likert scale from 1 (N/A), 2 (Never), 3 (Rarely), 4 ( Now and then), 5 (Often). Child inventory uses a 4 point Likert scale 1 (N/A), 2 (Never), 3 (Now and then), 5 (Always). Values are scores as follows 1=0, 2=1, 3=2, 4=3, 5=4. Score interpretation is 0 to 100 percent IMPACT of anticoagulation on a child's life therefore, higher scores indicates a more negative effect.

Outcome measures

Outcome measures
Measure	Apixaban n=46 Participants Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between \>/= 3 and \< 35 kg will be administered apixaban twice daily (BID) in doses between 0.2mg and 4 mg depending on body weight. Children randomized to the apixaban arm of the study weighing \>/= 35 kg will be administered apixaban 5 mg twice daily (BID).	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA) n=30 Participants Participants receive thromboprophylaxis with VKA or LMWH for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants who receive LMWH are allowed to switch to VKA at any time during the study; conversely, Participants having difficulty with VKA may switch to LMWH.	Participants Weight Range 12 to < 18 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 12 to \< 18 kg will be administered 2mg apixaban twice daily (BID).	Participants Weight Range 18 to < 25 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 18 to \< 25 kg will be administered 3mg apixaban twice daily (BID).	Participants Weight Range 25 to < 35 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between 25 to \< 35 kg will be administered 4mg apixaban twice daily (BID).	Participants Weight Range ≥ 35 kg Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between ≥ 35 kg will be administered 5mg apixaban twice daily (BID).
Kids Informed Decrease Complications Learning on Thrombosis (KIDCLOT) IMPACT Score BASELINE CHILD REPORTED - 6 MONTHS	24.35 Score on a scale Standard Deviation 12.887	26.45 Score on a scale Standard Deviation 12.114	—	—	—	—
Kids Informed Decrease Complications Learning on Thrombosis (KIDCLOT) IMPACT Score POST BASELINE CHILD REPORTED - 6 MONTHS	22.81 Score on a scale Standard Deviation 13.380	22.57 Score on a scale Standard Deviation 16.049	—	—	—	—
Kids Informed Decrease Complications Learning on Thrombosis (KIDCLOT) IMPACT Score BASELINE CHILD REPORTED - 12 MONTHS	22.50 Score on a scale Standard Deviation 11.787	25.32 Score on a scale Standard Deviation 11.719	—	—	—	—
Kids Informed Decrease Complications Learning on Thrombosis (KIDCLOT) IMPACT Score POST BASELINE CHILD REPORTED - 12 MONTHS	21.52 Score on a scale Standard Deviation 13.251	18.01 Score on a scale Standard Deviation 10.408	—	—	—	—
Kids Informed Decrease Complications Learning on Thrombosis (KIDCLOT) IMPACT Score BASELINE PARENT REPORTED - 6 MONTHS	37.97 Score on a scale Standard Deviation 20.493	39.02 Score on a scale Standard Deviation 17.932	—	—	—	—
Kids Informed Decrease Complications Learning on Thrombosis (KIDCLOT) IMPACT Score POST BASELINE PARENT REPORTED - 6 MONTHS	32.32 Score on a scale Standard Deviation 17.060	37.94 Score on a scale Standard Deviation 20.626	—	—	—	—
Kids Informed Decrease Complications Learning on Thrombosis (KIDCLOT) IMPACT Score BASELINE PARENT REPORTED - 12 MONTHS	38.37 Score on a scale Standard Deviation 18.874	39.36 Score on a scale Standard Deviation 16.057	—	—	—	—
Kids Informed Decrease Complications Learning on Thrombosis (KIDCLOT) IMPACT Score POST BASELINE PARENT REPORTED - 12 MONTHS	31.10 Score on a scale Standard Deviation 16.021	33.61 Score on a scale Standard Deviation 17.943	—	—	—	—

Adverse Events

Apixaban

Serious events: 26 serious events

Other events: 68 other events

Deaths: 0 deaths

Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA)

Serious events: 13 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Apixaban n=126 participants at risk Participants receive thromboprophylaxis with open-label apixaban for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants weighing between \>/= 3 and \< 35 kg will be administered apixaban twice daily (BID) in doses between 0.2mg and 4 mg depending on body weight. Children randomized to the apixaban arm of the study weighing \>/= 35 kg will be administered apixaban 5 mg twice daily (BID).	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA) n=62 participants at risk Participants receive thromboprophylaxis with VKA or LMWH for up to 12 months or until the need for anticoagulant is resolved, whichever occurs first. Participants who receive LMWH are allowed to switch to VKA at any time during the study; conversely, Participants having difficulty with VKA may switch to LMWH.
Gastrointestinal disorders Diarrhoea	9.5% 12/126 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)	6.5% 4/62 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)
Gastrointestinal disorders Vomiting	15.9% 20/126 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)	14.5% 9/62 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)
General disorders Pyrexia	15.9% 20/126 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)	12.9% 8/62 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)
Infections and infestations Gastroenteritis	5.6% 7/126 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)	6.5% 4/62 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)
Infections and infestations Nasopharyngitis	10.3% 13/126 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)	12.9% 8/62 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)
Infections and infestations Upper respiratory tract infection	11.1% 14/126 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)	6.5% 4/62 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)
Injury, poisoning and procedural complications Contusion	7.1% 9/126 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)	8.1% 5/62 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)
Investigations International normalised ratio increased	0.00% 0/126 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)	6.5% 4/62 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)
Nervous system disorders Dizziness	3.2% 4/126 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)	6.5% 4/62 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)
Nervous system disorders Headache	15.1% 19/126 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)	4.8% 3/62 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)
Respiratory, thoracic and mediastinal disorders Cough	6.3% 8/126 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)	6.5% 4/62 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)
Respiratory, thoracic and mediastinal disorders Epistaxis	15.9% 20/126 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)	9.7% 6/62 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)
Vascular disorders Haematoma	6.3% 8/126 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)	1.6% 1/62 • AEs are collected from the first dose date until the last dose date + 2 days/ SAEs are collected from the first dose date until the last dose date + 30 days (Up to approximately 13 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 57 months)

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