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

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02981472
• Collaborator: Pediatric Heart Network (Other), Pfizer (Industry)
• Enrollment: 192
• Locations: 46
• Arms: 2
• Actual Duration (Months): 56.9
• Patients Per Site: 4.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To investigate the safety and pharmacokinetics of apixaban in children with congenital or acquired heart disease who have a need for anticoagulation.

Condition or Disease	Intervention/Treatment	Phase
Thrombosis	Drug: Apixaban; Drug: Vitamin K Antagonist (VKA); Drug: Low Molecular Weight Heparin (LMWH)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 192 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Randomized, Open Label, Multi-center Study of the Safety and Pharmacokinetics of Apixaban Versus Vitamin K Antagonist or LMWH in Pediatric Subjects With Congenital or Acquired Heart Disease Requiring Chronic Anticoagulation for Thromboembolism Prevention
• Actual Study Start Date: Jan 19, 2017
• Actual Primary Completion Date: Oct 18, 2021
• Actual Study Completion Date: Oct 18, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Apixaban	Drug: Apixaban; Specified dose on specified days; Other Names: Eliquis
Active Comparator: LMWH/VKA	Drug: Vitamin K Antagonist (VKA); Specified dose on specified days; Other Names: Warfarin ; Drug: Low Molecular Weight Heparin (LMWH); Specified dose on specified days; Other Names: Enoxaparin

Outcome Measures

Primary Outcome Measures

1. Composite of Adjudicated Major or Clinically Relevant Non-Major (CRNM) Bleeding Events [From first dose to 2 days after last dose (Up to approximately 12 months)]

   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.

Secondary Outcome Measures

1. The Number of Participants With Thrombotic Events and Thromboembolic Event-Related Death [From randomization to 2 days after last dose (Up to approximately 12 months)]

   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)

2. The Number of Participants With Adjudicated Major Bleeding [From first dose to 2 days after last dose (Up to approximately 12 months)]

   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

3. The Number of Participants With Adjudicated CRNM Bleeding [From first dose to 2 days after last dose (Up to approximately 12 months)]

   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

4. The Number of Participants With All Adjudicated Bleeding [From first dose to 2 days after last dose (Up to approximately 12 months)]

   The number of participants with all adjudicated bleeding events

5. The Number of Participants With Drug Discontinuation Due to Adverse Effects, Intolerability, or Bleeding [From first dose to 2 days after last dose (Up to approximately 12 months)]

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

6. The Number of Participant Deaths in the Study [From first dose to 2 days after last dose (Up to approximately 12 months)]

   The number of participant deaths in the study.

7. Maximum Observed Concentration (Cmax) [From first dose up to 6 months after first dose]

8. Trough Observed Concentration (Cmin) [From first dose up to 6 months after first dose]

9. Area Under the Concentration-Time Curve in One Dosing Interval (AUC (TAU)) [From first dose up to 6 months after first dose]

10. Time of Maximum Observed Concentration (Tmax) [From first dose up to 6 months after first dose]

11. Anti-FXa Activity [From first dose up to 6 months after first dose]

    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.

12. Chromogenic FX Assay (Apparent FX Level) [From first dose up to 6 months after first dose]

    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.

13. The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL) [from randomization up to 12 months after randomization]

    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.

14. Kids Informed Decrease Complications Learning on Thrombosis (KIDCLOT) IMPACT Score [from randomization up to 12 months after randomization]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 28 Days to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Males and Females, 28 days to < 18 years of age, inclusive

• Congenital or acquired heart diseases requiring chronic anticoagulation for thromboprophylaxis (eg, single ventricle physiology including all 3 stages of palliation, dilated cardiomyopathy, Kawasaki disease with coronary aneurysms, and pulmonary hypertension)

• Eligible participants include those who newly start anticoagulants and those who are currently on VKA or LMWH or other anticoagulants for thromboprophylaxis

• Able to tolerate enteral medication [eg, by mouth, nasogastric tube, or gastric tube]

• Participants 28 days to < 3 months must be able to tolerate oral/nasogastric tube (NGT)/gastric tube (GT) feeds for at least 5 days prior to randomization

Exclusion Criteria:

• Recent thromboembolic events less than 6 months prior to enrollment

• Weight < 3 kg

• Use of aggressive life-saving therapies such as ventricular assist devices (VAD) or extracorporeal membrane oxygenation (ECMO) at the time of enrollment

• Artificial heart valves and mechanical heart valves

• Known inherited bleeding disorder or coagulopathy (e.g. hemophilia, von Willebrand disease, etc.)

• Active bleeding at the time of enrollment

• Any major bleeding other than perioperative in the preceding 3 months

• Known intracranial congenital vascular malformation or tumor

• Confirmed diagnosis of a GI ulcer

• Known antiphospholipid syndrome (APS).

Other protocol defined inclusion/exclusion criteria apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Children'S Hospital	Phoenix	Arizona	United States	85016
2	University Of California San Diego	La Jolla	California	United States	92093-0641
3	Children'S Hospital Colorado	Aurora	Colorado	United States	80045
4	Childrens Healthcare Of Atlanta	Atlanta	Georgia	United States	30322
5	Riley Hospital For Children	Indianapolis	Indiana	United States	46202
6	Boston Childrens Hospital	Boston	Massachusetts	United States	02115
7	University Of Michigan	Ann Arbor	Michigan	United States	48109
8	Childrens Mercy Hospital	Kansas City	Missouri	United States	64108
9	Cincinnati Childrens Hospital Medical Center	Cincinnati	Ohio	United States	45229
10	Childrens Hospital Of Philadelphia	Philadelphia	Pennsylvania	United States	19104
11	Medical University Of South Carolina	Charleston	South Carolina	United States	29425
12	Texas Children'S Hospital	Houston	Texas	United States	77030-2399
13	Primary Children's Hospital	Salt Lake City	Utah	United States	84113
14	Seattle Childrens Hospital	Seattle	Washington	United States	98105
15	Local Institution	Caba	Buenos Aires	Argentina	1426
16	Local Institution	Parkville	Victoria	Australia	3052
17	Medical University Of Vienna	Vienna		Austria	1090
18	Hospital Pequeno Principe	Curitiba	Parana	Brazil	80250-060
19	Instituto De Cardiologia Do Rio Grande Do Sul	Porto Alegre	Rio Grande Do Sul	Brazil	90620-001
20	Instituto de Pesquisa Clinica de Campinas	Campinas	Sao Paulo	Brazil	13060-080
21	Instituto de Pesquisa PENSI	Sao Paulo		Brazil	01227-200
22	Universidade Federal De Sao Paulo	Sao Paulo		Brazil	04024-002
23	Local Institution	Toronto	Ontario	Canada	M5G 1X8
24	Local Institution	HUS		Finland	00029
25	Universitaetsklinikum Freiburg Kinderklinik	Freiburg		Germany	79106
26	Local Institution - 0004	Hamburg		Germany	20246
27	Local Institution - 0003	Muenchen		Germany	80636
28	Local Institution	Petach Tikva		Israel
29	Local Institution	Tel Hashomer		Israel	52620
30	Local Institution - 0026	Rome	Roma	Italy	00165
31	Local Institution	Bologna		Italy	40138
32	Policlinico San Donato	Milano		Italy	20097
33	Local Institution	Mexico City	Distrito Federal	Mexico	04530
34	Local Institution	Mexico City	Distrito Federal	Mexico	06720
35	Local Institution	Mexico City	Distrito Federal	Mexico	14080
36	Morales Vargas Centro de Investigacion, S.C.	Leon	Guanajuato	Mexico	37000
37	Local Institution	Ekaterinburg		Russian Federation	620134
38	Local Institution	Kazan		Russian Federation	420012
39	Local Institution	Kemerovo		Russian Federation	650002
40	Local Institution	Novosibirsk		Russian Federation	630055
41	Local Institution	Barcelona		Spain	08950
42	Local Institution	Madrid		Spain	28007
43	Local Institution	Madrid		Spain	28046
44	Local Institution	Leicester	Leicestershire	United Kingdom	LE3 9QP
45	Local Institution	Bristol	Somerset	United Kingdom	BS2 8BJ
46	Local Institution	Manchester		United Kingdom	M13 9WL

Sponsors and Collaborators

• Bristol-Myers Squibb
• Pediatric Heart Network
• Pfizer

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 16, 2020

More Information

Additional Information:

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02981472
• Other Study ID Numbers: CV185-362; 2016-001247-39
• First Posted: Dec 5, 2016
• Last Update Posted: May 18, 2022
• Last Verified: May 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Heart Diseases; Thrombosis; Vitamin K; Heparin; Enoxaparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin; Warfarin; Apixaban

Study Results

Participant Flow

Pre-assignment Detail	192 participants were randomized and 188 received treatment

Arm/Group Title	Apixaban	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA)
Arm/Group Description	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).	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.
Period Title: Pre-Treatment Period
STARTED	129	63
COMPLETED	126	62
NOT COMPLETED	3	1
Period Title: Pre-Treatment Period
STARTED	126	62
COMPLETED	119	60
NOT COMPLETED	7	2

Baseline Characteristics

Arm/Group Title	Apixaban	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA)	Total
Arm/Group Description	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).	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 of all reporting groups
Overall Participants	129	63	192
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	7.96 (4.553)	7.56 (4.408)	7.83 (4.499)
Age, Customized (Count of Participants)
28 DAYS - < 2 YEARS	8 6.2%	3 4.8%	11 5.7%
2 YEARS - < 6 YEARS	40 31%	22 34.9%	62 32.3%
6 YEARS - < 12 YEARS	49 38%	23 36.5%	72 37.5%
12 YEARS - < 18 YEARS	32 24.8%	15 23.8%	47 24.5%
Sex: Female, Male (Count of Participants)
Female	67 51.9%	23 36.5%	90 46.9%
Male	62 48.1%	40 63.5%	102 53.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	20 15.5%	14 22.2%	34 17.7%
Not Hispanic or Latino	105 81.4%	47 74.6%	152 79.2%
Unknown or Not Reported	4 3.1%	2 3.2%	6 3.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.8%	0 0%	1 0.5%
Asian	6 4.7%	4 6.3%	10 5.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 5.4%	2 3.2%	9 4.7%
White	109 84.5%	51 81%	160 83.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	6 4.7%	6 9.5%	12 6.3%

Outcome Measures

1. Primary Outcome

Title	Composite of Adjudicated Major or Clinically Relevant Non-Major (CRNM) Bleeding Events
Description	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.
Time Frame	From first dose to 2 days after last dose (Up to approximately 12 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Apixaban	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA)
Arm/Group Description	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).	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.
Measure Participants	126	62
Count of Participants [Participants]	1 0.8%	3 4.8%

2. Secondary Outcome

Title	The Number of Participants With Thrombotic Events and Thromboembolic Event-Related Death
Description	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)
Time Frame	From randomization to 2 days after last dose (Up to approximately 12 months)

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Apixaban	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA)
Arm/Group Description	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).	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.
Measure Participants	129	63
Thromboembolic event	0 0%	0 0%
Thromboembolic event-related death	0 0%	0 0%

3. Secondary Outcome

Title	The Number of Participants With Adjudicated Major Bleeding
Description	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
Time Frame	From first dose to 2 days after last dose (Up to approximately 12 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Apixaban	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA)
Arm/Group Description	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).	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.
Measure Participants	126	62
Count of Participants [Participants]	1 0.8%	1 1.6%

4. Secondary Outcome

Title	The Number of Participants With Adjudicated CRNM Bleeding
Description	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
Time Frame	From first dose to 2 days after last dose (Up to approximately 12 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Apixaban	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA)
Arm/Group Description	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).	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.
Measure Participants	126	62
Count of Participants [Participants]	1 0.8%	2 3.2%

5. Secondary Outcome

Title	The Number of Participants With All Adjudicated Bleeding
Description	The number of participants with all adjudicated bleeding events
Time Frame	From first dose to 2 days after last dose (Up to approximately 12 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Apixaban	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA)
Arm/Group Description	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).	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.
Measure Participants	126	62
Count of Participants [Participants]	47 36.4%	23 36.5%

6. Secondary Outcome

Title	The Number of Participants With Drug Discontinuation Due to Adverse Effects, Intolerability, or Bleeding
Description	The number of participants with drug discontinuation due to adverse effects, intolerability, or bleeding.
Time Frame	From first dose to 2 days after last dose (Up to approximately 12 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Apixaban	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA)
Arm/Group Description	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).	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.
Measure Participants	126	62
Count of Participants [Participants]	7 5.4%	1 1.6%

7. Secondary Outcome

Title	The Number of Participant Deaths in the Study
Description	The number of participant deaths in the study.
Time Frame	From first dose to 2 days after last dose (Up to approximately 12 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Apixaban	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA)
Arm/Group Description	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).	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.
Measure Participants	126	62
Count of Participants [Participants]	0 0%	0 0%

8. Secondary Outcome

Title	Maximum Observed Concentration (Cmax)
Time Frame	From first dose up to 6 months after first dose

Outcome Measure Data

Analysis Population Description

All treated participants in the apixaban arm with available pharmacokinetic data

Arm/Group Title	Participants Weight Range 6 to < 9 kg	Participants Weight Range 9 to < 12 kg	Participants Weight Range 12 to < 18 kg	Participants Weight Range 18 to < 25 kg	Participants Weight Range 25 to < 35 kg	Participants Weight Range ≥ 35 kg
Arm/Group Description	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 6 to < 9 kg will be administered 1mg apixaban twice daily (BID).	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 9 to < 12 kg will be administered 1.5mg apixaban twice daily (BID).	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 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 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 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).
Measure Participants	6	2	28	29	24	35
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	185 (48.8)	218 (23.4)	222 (39.6)	244 (30.7)	249 (37.7)	203 (35.9)

9. Secondary Outcome

Title	Trough Observed Concentration (Cmin)
Time Frame	From first dose up to 6 months after first dose

Outcome Measure Data

Analysis Population Description

All treated participants in the apixaban arm with available pharmacokinetic data

Arm/Group Title	Participants Weight Range 6 to < 9 kg	Participants Weight Range 9 to < 12 kg	Participants Weight Range 12 to < 18 kg	Participants Weight Range 18 to < 25 kg	Participants Weight Range 25 to < 35 kg	Participants Weight Range ≥ 35 kg
Arm/Group Description	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 6 to < 9 kg will be administered 1mg apixaban twice daily (BID).	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 9 to < 12 kg will be administered 1.5mg apixaban twice daily (BID).	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 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 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 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).
Measure Participants	6	2	28	29	24	35
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	57.9 (90.3)	82.7 (21.5)	64.3 (69.5)	67.4 (58.9)	73.1 (64.7)	72.7 (46.8)

10. Secondary Outcome

Title	Area Under the Concentration-Time Curve in One Dosing Interval (AUC (TAU))
Time Frame	From first dose up to 6 months after first dose

Outcome Measure Data

Analysis Population Description

All treated participants in the apixaban arm with available pharmacokinetic data

Arm/Group Title	Participants Weight Range 6 to < 9 kg	Participants Weight Range 9 to < 12 kg	Participants Weight Range 12 to < 18 kg	Participants Weight Range 18 to < 25 kg	Participants Weight Range 25 to < 35 kg	Participants Weight Range ≥ 35 kg
Arm/Group Description	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 6 to < 9 kg will be administered 1mg apixaban twice daily (BID).	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 9 to < 12 kg will be administered 1.5mg apixaban twice daily (BID).	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 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 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 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).
Measure Participants	6	2	28	29	24	35
Geometric Mean (Geometric Coefficient of Variation) [ng • h/mL]	1460 (61.2)	1840 (20.7)	1610 (49.6)	1760 (38.3)	1840 (43.3)	1630 (37.3)

11. Secondary Outcome

Title	Time of Maximum Observed Concentration (Tmax)
Time Frame	From first dose up to 6 months after first dose

Outcome Measure Data

Analysis Population Description

All treated participants in the apixaban arm with available pharmacokinetic data

Arm/Group Title	Participants Weight Range 6 to < 9 kg	Participants Weight Range 9 to < 12 kg	Participants Weight Range 12 to < 18 kg	Participants Weight Range 18 to < 25 kg	Participants Weight Range 25 to < 35 kg	Participants Weight Range ≥ 35 kg
Arm/Group Description	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 6 to < 9 kg will be administered 1mg apixaban twice daily (BID).	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 9 to < 12 kg will be administered 1.5mg apixaban twice daily (BID).	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 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 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 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).
Measure Participants	6	2	28	29	24	35
Median (Full Range) [hours]	2.24	2.47	1.72	1.74	1.65	1.85

12. Secondary Outcome

Title	Anti-FXa Activity
Description	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.
Time Frame	From first dose up to 6 months after first dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Apixaban
Arm/Group Description	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).
Measure Participants	125
Day 1 (4 HRS POSTDOSE)	147.69 (7.243)
Week 2 (PREDOSE)	86.24 (7.652)
Week 2 (2 HRS POSTDOSE)	242.34 (18.966)
Month 3 (2 HRS POSTDOSE)	228.88 (14.263)
Month 6 (PREDOSE)	66.93 (6.532)

13. Secondary Outcome

Title	Chromogenic FX Assay (Apparent FX Level)
Description	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.
Time Frame	From first dose up to 6 months after first dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Apixaban
Arm/Group Description	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).
Measure Participants	125
Day 1 (PREDOSE)	58.87 (2.368)
Day 1 (4 HRS POSTDOSE)	18.90 (1.205)
Week 2 (PREDOSE)	35.88 (1.973)
Week 2 (2 HRS POSTDOSE)	21.26 (1.680)
Month 3 (2 HRS POSTDOSE)	18.25 (0.970)
Month 6 (PREDOSE)	36.57 (1.943)

14. Secondary Outcome

Title	The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL)
Description	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.
Time Frame	from randomization up to 12 months after randomization

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Apixaban	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA)
Arm/Group Description	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).	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.
Measure Participants	129	63
GENERAL-SPECIFIC MODULE ASSESSED BY CHILD - BASELINE	69.64 (15.512)	60.71 (17.374)
GENERAL-SPECIFIC MODULE ASSESSED BY CHILD - MONTH 12	73.37 (19.998)	64.81 (22.327)
GENERAL-SPECIFIC MODULE ASSESSED BY PARENT - BASELINE	65.61 (16.625)	65.42 (18.000)
GENERAL-SPECIFIC MODULE ASSESSED BY PARENT - MONTH 12	70.00 (19.560)	70.32 (21.949)
HEART PROBLEMS AND TREATMENT ASSESSED BY CHILD - BASELINE	65.34 (22.130)	64.70 (18.465)
HEART PROBLEMS AND TREATMENT ASSESSED BY CHILD - MONTH 12	69.46 (21.119)	63.44 (19.836)
TREATMENT II ASSESSED BY CHILD - BASELINE	87.39 (22.994)	85.68 (15.857)
TREATMENT II ASSESSED BY CHILD - MONTH 12	91.77 (10.896)	86.27 (16.400)
PERCEIVED PHYSICAL APPEARANCE ASSESSED BY CHILD - BASELINE	75.51 (27.477)	78.44 (23.390)
PERCEIVED PHYSICAL APPEARANCE ASSESSED BY CHILD - MONTH 12	80.56 (22.408)	81.37 (30.689)
TREATMENT ANXIETY ASSESSED BY CHILD - BASELINE	80.52 (23.420)	60.31 (34.162)
TREATMENT ANXIETY ASSESSED BY CHILD - MONTH 12	80.71 (25.480)	60.31 (38.333)
COGNITIVE PROBLEMS ASSESSED BY CHILD - BASELINE	69.85 (20.871)	53.24 (20.382)
COGNITIVE PROBLEMS ASSESSED BY CHILD - MONTH 12	68.24 (24.367)	53.53 (26.796)
COMMUNICATION ASSESSED BY CHILD - BASELINE	66.15 (30.000)	63.55 (28.998)
COMMUNICATION ASSESSED BY CHILD - MONTH 12	70.31 (26.681)	57.28 (38.948)
HEART PROBLEMS AND TREATMENT ASSESSED BY PARENT - BASELINE	63.68 (20.727)	67.71 (22.668)
HEART PROBLEMS AND TREATMENT ASSESSED BY PARENT - MONTH 12	66.37 (20.811)	69.00 (23.688)
TREATMENT II ASSESSED BY PARENT - BASELINE	91.41 (11.557)	85.27 (17.325)
TREATMENT II ASSESSED BY PARENT - MONTH 12	90.30 (12.381)	83.80 (18.915)
PERCEIVED PHYSICAL APPEARANCE ASSESSED BY PARENT - BASELINE	79.16 (22.571)	79.66 (22.958)
PERCEIVED PHYSICAL APPEARANCE ASSESSED BY PARENT - MONTH 12	79.38 (21.012)	74.33 (26.998)
TREATMENT ANXIETY ASSESSED BY PARENT - BASELINE	61.44 (30.804)	56.27 (33.997)
TREATMENT ANXIETY ASSESSED BY PARENT - MONTH 12	64.03 (29.567)	57.77 (34.199)
COGNITIVE PROBLEMS ASSESSED BY PARENT - BASELINE	60.29 (29.558)	61.60 (25.807)
COGNITIVE PROBLEMS ASSESSED BY PARENT - MONTH 12	58.69 (29.560)	58.53 (33.432)
COMMUNICATION ASSESSED BY PARENT - BASELINE	65.57 (27.342)	67.33 (28.257)
COMMUNICATION ASSESSED BY PARENT - MONTH 12	68.20 (24.037)	66.17 (28.067)

15. Secondary Outcome

Title	Kids Informed Decrease Complications Learning on Thrombosis (KIDCLOT) IMPACT Score
Description	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.
Time Frame	from randomization up to 12 months after randomization

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Apixaban	Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA)
Arm/Group Description	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).	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.
Measure Participants	46	30
BASELINE CHILD REPORTED - 6 MONTHS	24.35 (12.887)	26.45 (12.114)
POST BASELINE CHILD REPORTED - 6 MONTHS	22.81 (13.380)	22.57 (16.049)
BASELINE CHILD REPORTED - 12 MONTHS	22.50 (11.787)	25.32 (11.719)
POST BASELINE CHILD REPORTED - 12 MONTHS	21.52 (13.251)	18.01 (10.408)
BASELINE PARENT REPORTED - 6 MONTHS	37.97 (20.493)	39.02 (17.932)
POST BASELINE PARENT REPORTED - 6 MONTHS	32.32 (17.060)	37.94 (20.626)
BASELINE PARENT REPORTED - 12 MONTHS	38.37 (18.874)	39.36 (16.057)
POST BASELINE PARENT REPORTED - 12 MONTHS	31.10 (16.021)	33.61 (17.943)

Adverse Events

Time Frame	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)
Arm/Group Title	Apixaban		Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA)
Arm/Group Description	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).		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.
All Cause Mortality
	Apixaban		Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/126 (0%)		0/62 (0%)
Serious Adverse Events
	Apixaban		Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/126 (20.6%)		13/62 (21%)
Cardiac disorders
Arrhythmia	1/126 (0.8%)		1/62 (1.6%)
Atrial septal defect acquired	0/126 (0%)		1/62 (1.6%)
Cardiac dysfunction	1/126 (0.8%)		0/62 (0%)
Cardiac failure	1/126 (0.8%)		0/62 (0%)
Cardiac failure congestive	1/126 (0.8%)		0/62 (0%)
Supraventricular tachycardia	0/126 (0%)		1/62 (1.6%)
Ventricular fibrillation	1/126 (0.8%)		0/62 (0%)
Congenital, familial and genetic disorders
Congenital cystic kidney disease	0/126 (0%)		1/62 (1.6%)
Hypoplastic left heart syndrome	0/126 (0%)		1/62 (1.6%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	1/126 (0.8%)		0/62 (0%)
Gingival bleeding	0/126 (0%)		1/62 (1.6%)
Haematochezia	0/126 (0%)		1/62 (1.6%)
Inguinal hernia	1/126 (0.8%)		0/62 (0%)
Protein-losing gastroenteropathy	1/126 (0.8%)		1/62 (1.6%)
General disorders
Generalised oedema	1/126 (0.8%)		0/62 (0%)
Impaired healing	1/126 (0.8%)		0/62 (0%)
Infections and infestations
COVID-19	1/126 (0.8%)		1/62 (1.6%)
Dengue fever	1/126 (0.8%)		0/62 (0%)
Gastroenteritis	1/126 (0.8%)		0/62 (0%)
Influenza	1/126 (0.8%)		1/62 (1.6%)
Nasopharyngitis	1/126 (0.8%)		0/62 (0%)
Pneumonia viral	0/126 (0%)		1/62 (1.6%)
Respiratory syncytial virus bronchiolitis	1/126 (0.8%)		0/62 (0%)
Sepsis	1/126 (0.8%)		0/62 (0%)
Viral upper respiratory tract infection	1/126 (0.8%)		0/62 (0%)
Injury, poisoning and procedural complications
Contusion	1/126 (0.8%)		1/62 (1.6%)
Incorrect dose administered	1/126 (0.8%)		0/62 (0%)
Overdose	1/126 (0.8%)		0/62 (0%)
Post procedural haematoma	1/126 (0.8%)		0/62 (0%)
Procedural complication	1/126 (0.8%)		0/62 (0%)
Procedural haemorrhage	1/126 (0.8%)		0/62 (0%)
Rib fracture	0/126 (0%)		1/62 (1.6%)
Shunt thrombosis	2/126 (1.6%)		0/62 (0%)
Spinal fracture	0/126 (0%)		1/62 (1.6%)
Subdural haematoma	0/126 (0%)		1/62 (1.6%)
Toxicity to various agents	0/126 (0%)		1/62 (1.6%)
Vascular pseudoaneurysm	1/126 (0.8%)		0/62 (0%)
Investigations
International normalised ratio increased	0/126 (0%)		1/62 (1.6%)
Intracardiac pressure increased	0/126 (0%)		1/62 (1.6%)
Pulmonary arterial pressure increased	1/126 (0.8%)		0/62 (0%)
Metabolism and nutrition disorders
Dehydration	0/126 (0%)		1/62 (1.6%)
Musculoskeletal and connective tissue disorders
Pain in extremity	0/126 (0%)		1/62 (1.6%)
Nervous system disorders
Seizure	1/126 (0.8%)		0/62 (0%)
Syncope	1/126 (0.8%)		0/62 (0%)
Psychiatric disorders
Suicidal ideation	1/126 (0.8%)		0/62 (0%)
Suicide attempt	1/126 (0.8%)		0/62 (0%)
Renal and urinary disorders
Acute kidney injury	1/126 (0.8%)		0/62 (0%)
Haematuria	1/126 (0.8%)		0/62 (0%)
Reproductive system and breast disorders
Penile haematoma	1/126 (0.8%)		0/62 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/126 (0.8%)		0/62 (0%)
Hypoxia	0/126 (0%)		1/62 (1.6%)
Pleural effusion	1/126 (0.8%)		1/62 (1.6%)
Pneumothorax spontaneous	0/126 (0%)		1/62 (1.6%)
Pulmonary haemorrhage	0/126 (0%)		1/62 (1.6%)
Other (Not Including Serious) Adverse Events
	Apixaban		Low Molecular Weight Heparin (LMWH)/Vitamin K Antagonists (VKA)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	68/126 (54%)		36/62 (58.1%)
Gastrointestinal disorders
Diarrhoea	12/126 (9.5%)		4/62 (6.5%)
Vomiting	20/126 (15.9%)		9/62 (14.5%)
General disorders
Pyrexia	20/126 (15.9%)		8/62 (12.9%)
Infections and infestations
Gastroenteritis	7/126 (5.6%)		4/62 (6.5%)
Nasopharyngitis	13/126 (10.3%)		8/62 (12.9%)
Upper respiratory tract infection	14/126 (11.1%)		4/62 (6.5%)
Injury, poisoning and procedural complications
Contusion	9/126 (7.1%)		5/62 (8.1%)
Investigations
International normalised ratio increased	0/126 (0%)		4/62 (6.5%)
Nervous system disorders
Dizziness	4/126 (3.2%)		4/62 (6.5%)
Headache	19/126 (15.1%)		3/62 (4.8%)
Respiratory, thoracic and mediastinal disorders
Cough	8/126 (6.3%)		4/62 (6.5%)
Epistaxis	20/126 (15.9%)		6/62 (9.7%)
Vascular disorders
Haematoma	8/126 (6.3%)		1/62 (1.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.