A Study of the Safety and Effectiveness of Apixaban in Preventing Blood Clots in Children With Leukemia Who Have a Central Venous Catheter and Are Treated With Asparaginase

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02369653
• Collaborator: Pfizer (Industry)
• Enrollment: 512
• Locations: 96
• Arms: 2
• Actual Duration (Months): 68.5
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the effect of a blood thinning drug called Apixaban versus no administration of a blood thinning drug, in preventing blood clots in children with leukemia or lymphoma. Patients must be receiving chemotherapy, including asparaginase, and have a central line (a catheter inserted for administration of medications and blood sampling)

Condition or Disease	Intervention/Treatment	Phase
Lymphoma; Acute Lymphoblastic Leukemia	Drug: Apixaban; Other: No systemic anticoagulant prophylaxis	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 512 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase III Randomized, Open Label, Multi-center Study of the Safety and Efficacy of Apixaban for Thromboembolism Prevention Versus No Systemic Anticoagulant Prophylaxis During Induction Chemotherapy in Children With Newly Diagnosed Acute Lymphoblastic Leukemia (ALL) or Lymphoma (T or B Cell) Treated With Asparaginase
• Actual Study Start Date: Oct 22, 2015
• Actual Primary Completion Date: Jul 7, 2021
• Actual Study Completion Date: Jul 7, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Apixaban Children aged 1 to <18 years weighing 6 to <35 kg randomized to apixaban will receive a fixed dose apixaban based on body weight tier twice a day for approximately 28 days. Children aged 1 to <18 years weighing ≥ 35 kg will receive 2.5 mg of apixaban twice a day for approximately 28 days. Subjects ≥ 5 years may be administered either 2.5-mg, 0.5-mg tablets or oral solution apixaban. Subjects < 5years and < 35 kg may be administered 0.5-mg tablets only	Drug: Apixaban
Placebo Comparator: No systemic anticoagulant prophylaxis No systemic anticoagulant prophylaxis	Other: No systemic anticoagulant prophylaxis

Outcome Measures

Primary Outcome Measures

1. The Number of Participants With Non-Fatal DVT, PE, and CVST, and VTE-Related-Death [From first dose up to approximately 40 days after first dose]

   The number of participants with non-fatal deep vein thromboses (DVT) (including asymptomatic and symptomatic), pulmonary embolism (PE), cerebral venous sinus thrombosis (CVST); and venous thromboembolism (VTE) related-death objectively confirmed by a blinded, independent adjudication committee. Symptomatic events are included during the intended treatment period. Asymptomatic events are included from scans up to Day 40.

2. The Number of Participants With Adjudicated Major Bleeding [From first dose up to approximately 34 days after first dose]

   The number of participants with major bleeding adjudicated by a blinded, independent adjudication committee. Adjudicated 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 20g/L (ie, 2g/dL) in a 24-hour period bleeding that is retroperitoneal, pulmonary, intracranial, or otherwise involves the CNS; and/or bleeding that requires surgical intervention in an operating suite, including interventional radiology.

Secondary Outcome Measures

1. The Number of Participants With Non-fatal Asymptomatic Deep Vein Thromboses (DVT) [From first dose up to approximately 40 days after first dose]

   The number of participants with non-fatal asymptomatic deep vein thromboses (DVT) adjudicated by a blinded, independent adjudication committee

2. The Number of Participants With Non-fatal Symptomatic Deep Vein Thromboses (DVT) [From first dose up to approximately 34 days after first dose]

   The number of participants with non-fatal symptomatic deep vein thromboses (DVT) adjudicated by a blinded, independent adjudication committee

3. The Number of Participants With Non-fatal Pulmonary Embolism (PE) [From first dose up to approximately 34 days after first dose]

   The number of participants with non-fatal pulmonary embolism (PE) adjudicated by a blinded, independent adjudication committee

4. The Number of Participants With Cerebral Venous Sinus Thrombosis (CVST) [From first dose up to approximately 34 days after first dose]

   The number of participants with cerebral venous sinus thrombosis (CVST) adjudicated by a blinded, independent adjudication committee

5. The Number of Participants With Venous Thromboembolism (VTE)-Related-death [From first dose up to approximately 34 days after first dose]

   The number of participants with venous thromboembolism (VTE)-related-death adjudicated by a blinded, independent adjudication committee

6. The Number of Participants With Major and Clinically Relevant Non-Major Bleeding (CRNMB) [From first dose up to approximately 34 days after first dose]

   The number of participants with major and clinically relevant non-major bleeding (CRNMB) adjudicated by a blinded, independent adjudication committee CRNM bleeding is defined as bleeding that satisfies one or both of the following: overt bleeding for which blood product is administered and not directly attributable to the subject's underlying medical condition and bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating room

7. The Number of Participant Deaths [From first dose date until the end of the treatment period + 30 days (Up to approximately 59 days)]

   The number of participant deaths adjudicated by a blinded, independent adjudication committee

8. The Number of Participants With an Arterial Thromboembolic Event [From first dose up to approximately 34 days after first dose]

   The number of participants with an arterial thromboembolic event including paradoxical embolism and stroke adjudicated by a blinded, independent adjudication committee

9. The Number of Participants With a CVAD-Related Infection [From first dose up to approximately 34 days after first dose]

   The number of participants with a central venous access device (CVAD)-related infection adjudicated by a blinded, independent adjudication committee

10. The Number of Participants Needing Catheter Replacements During the Study [From first dose up to approximately 34 days after first dose]

    The number of participants needing catheter replacements during the study

11. The Number of Participants With CVAD Patency Restoration Events After Thrombolytic Therapy Use [From first dose up to approximately 34 days after first dose]

    The number of participants with central venous access device (CVAD) patency restoration events after thrombolytic therapy use

12. The Number Participants Experiencing Superficial Vein Thrombosis Events [From first dose up to approximately 34 days after first dose]

    The number participants experiencing superficial vein thrombosis events. Clots that occur in a superficial vein ie, cephalic vein, basilic vein (upper extremity) or saphenous vein (lower extremity) confirmed by radiographic imaging.

13. The Number of Participants With Clinically Relevant Non-Major Bleeding Events (CRNMB) [From first dose up to approximately 34 days after first dose]

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

14. The Number of Participants With Minor Bleeding Events [From first dose up to approximately 34 days after first dose]

    The number of participants with minor bleeding events adjudicated by a blinded, independent adjudication committee. Minor bleeding defined as any overt or macroscopic evidence of bleeding that does not fulfill the criteria for either major bleeding or CRNMB

15. The Number of Platelet Transfusions Needed During the Study [From first dose up to approximately 34 days after first dose]

    The number of platelet transfusions needed during the study. The events are not adjudicated. A subject could have more than one platelet transfusion.

16. Maximum Observed Concentration (Cmax) [pre-dose, 1-4 hours post dose]

    The maximum observed concentration (Cmax) was measured to assess the pharmacokinetics of oral or enteric apixaban in pediatric subjects receiving induction chemotherapy.

17. Trough Observed Concentration (Cmin) [pre-dose, 1-4 hours post dose]

    The trough observed concentration (Cmin) was measured to assess the pharmacokinetics of oral or enteric apixaban in pediatric subjects receiving induction chemotherapy.

18. Area Under the Concentration-Time Curve [AUC(TAU)] [pre-dose, 1-4 hours post dose]

    The area under the concentration-time curve [AUC(TAU)] was measured to assess the pharmacokinetics of oral or enteric apixaban in pediatric subjects receiving induction chemotherapy.

19. Anti-FXa Activity [pre-dose and 2.5 hours after dosing on day 7. Day 8 and day 15.]

    Anti-FXa Activity was measured to characterize the relationship between apixaban plasma concentration and anti-FXa activity in pediatric subjects receiving induction chemotherapy

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• New diagnosis of de novo ALL, lymphomas (T or B cell), or mixed-phenotype acute leukemia

• Planned 3-4 drug systemic induction chemotherapy with a corticosteroid, vincristine and a single dose or multiple doses of asparaginase, with or without daunorubicin

• Functioning Central Venous Access Device

• Must be able to tolerate oral medication or have it administered via an Nasogastric tube (NGT) or GT tube

• Males and females,age 1 year(365 days) to < 18 (17 years and 364 days) years.

Exclusion Criteria:

• Subjects scheduled to have > 3 Lumbar Punctures over the course of the study treatment period

• Prior history of documented DVT or PE in the past 3 months

• Known inherited bleeding disorder or coagulopathy

• Major surgery [excluding Central Venous Access Device (CVAD) replacement and bone marrow aspiration and non-open biopsy] within the last 7 days prior to enrollment that may be associated with a risk of bleeding. Open biopsy is considered a major surgery.

• Uncontrolled severe hypertension at enrollment. Severe hypertension is defined as a systolic or diastolic blood pressure (BP) > 5 mm Hg above the 95th percentile as defined by the National High Blood Pressure Education Program Working Group (NHBPEP) established guidelines for the definition of normal and elevated blood pressure in children

• Extreme hyperleukocytosis, white blood cell (WBC) counts over 200 x 109/L (200,000/microL) at the time of enrollment

• Liver dysfunction manifested by SGTP (ALT) > 5X Upper limit of normal (ULN) and/or Aspartate aminotransferase (AST) >5 X ULN and/or direct (conjugated) bilirubin > 2X ULN

• Renal function < 30% of normal for age and size as determined by the Schwartz formula

• International normalized ratio (INR) > 1.4 and activated partial thromboplastin time (aPTT) > 3 seconds above the upper limit of normal for age, within 1 week prior to enrollment.

• History of allergy to apixaban or Factor Xa inhibitors

• History of significant adverse reaction or major bleeding related adverse reaction to other anticoagulant or antiplatelet agents

• History of any significant drug allergy (such as anaphylaxis or hepatotoxicity

• Any investigational drug being administered during the study

Other protocol inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Children'S Hospital/Ctr. For Cancer & Blood Ctr.	Phoenix	Arizona	United States	85016
2	City of Hope	Duarte	California	United States	91010
3	Loma Linda University Cancer Center	Loma Linda	California	United States	92350
4	Childrens Hospital Of La	Los Angeles	California	United States	90027
5	Children'S Hospital Of Orange County	Orange	California	United States	92868
6	Lucile Packard Children's Hospital (LPCH)	Palo Alto	California	United States	94304
7	Rady Children'S Hospital - San Diego	San Diego	California	United States	92123-4282
8	Connecticut Children's Medical Center	Hartford	Connecticut	United States	06106
9	Yale University School Of Medicine	New Haven	Connecticut	United States	06520
10	Nemours / A. I. duPont Hospital for Children	Wilmington	Delaware	United States	19803
11	Golisano Childrens Hospital of Southwest Florida	Fort Myers	Florida	United States	33908
12	Shands Hospital At University Of Florida	Gainesville	Florida	United States	32610-0298
13	Nemours Children'S Clinic	Jacksonville	Florida	United States	32207
14	Nemours Children'S Clinic - Orlando	Orlando	Florida	United States	32827
15	Nemours Children'S Clinic-Pensacola	Pensacola	Florida	United States	32504
16	All Childrens Hospital Specialty Physicians	Saint Petersburg	Florida	United States	33701
17	St. Marys Medical Center	West Palm Beach	Florida	United States	33407
18	Childrens Healthcare Of Atlanta - E	Atlanta	Georgia	United States	30342
19	Navicent Health Physician Group	Macon	Georgia	United States	31201
20	St. Luke'S Mountain State Tumor Institute	Boise	Idaho	United States	83712
21	Children'S Center For Cancer And Blood Diseases	Indianapolis	Indiana	United States	46260
22	Blank Childrens Hospital	Des Moines	Iowa	United States	50309
23	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
24	University of Kentucky	Lexington	Kentucky	United States	40536-0293
25	University Of Louisville	Louisville	Kentucky	United States	40202
26	Childrens Hospital New Orleans	New Orleans	Louisiana	United States	70118
27	Ochsner Medical Center	New Orleans	Louisiana	United States	70121
28	Sinai Hospital Of Baltimore	Baltimore	Maryland	United States	21215
29	Johns Hopkins University	Baltimore	Maryland	United States	21287
30	University Of Michigan Cancer Center	Ann Arbor	Michigan	United States	48109
31	Childrens Hospitals And Clinics Of Minnesota	Minneapolis	Minnesota	United States	55404
32	University Of Minnesota	Minneapolis	Minnesota	United States	55455
33	Mayo Clinic Rochester	Rochester	Minnesota	United States	55905
34	University Of Mississippi Medical Center	Jackson	Mississippi	United States	39216
35	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
36	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
37	Valerie Fund Children's Center at St. Joseph's Children's Hospital	Paterson	New Jersey	United States	07503
38	Albany Medical Center	Albany	New York	United States	12208
39	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
40	University Of Rochester General Clinical Research Center	Rochester	New York	United States	14642
41	SUNY Upstate Medical University	Syracuse	New York	United States	13210
42	New York Medical College	Valhalla	New York	United States	10595
43	Unv. Of Nc At Chapel Hill	Chapel Hill	North Carolina	United States	27599
44	Wake Forest Baptist Health	Winston-Salem	North Carolina	United States	27157
45	Akron Children'S Hospital	Akron	Ohio	United States	44308
46	Cincinnati Children'S Hospital Medical Center	Cincinnati	Ohio	United States	45229-3039
47	University Hospitals	Cleveland	Ohio	United States	44106
48	Nationwide Children'S Hospital	Columbus	Ohio	United States	43205
49	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania	United States	18017
50	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
51	Penn State Hershey Medical Center	Hershey	Pennsylvania	United States	17033
52	Childrens Hospital Of Philadelphia	Philadelphia	Pennsylvania	United States	19104
53	Children's Hospital Of Pittsburgh Of UPMC	Pittsburgh	Pennsylvania	United States	15224
54	Children's Hospital at TriStar Centennial	Nashville	Tennessee	United States	37203
55	Monroe Carell Jr Children'S Hosp. At Vanderbilt Tower	Nashville	Tennessee	United States	37232
56	Dell Children'S Medical Center Of Central Texas	Austin	Texas	United States	78723
57	Driscoll Children'S Hospital	Corpus Christi	Texas	United States	78411
58	Texas Children's Cancer and Hematology Centers	Houston	Texas	United States	77030
59	Children's Hospital of San Antonio	San Antonio	Texas	United States	78207
60	University Hospital	San Antonio	Texas	United States	78284
61	Scott & White - McLane Children's Specialty Clinic	Temple	Texas	United States	76502
62	Providence Sacred Heart Medical Center	Spokane	Washington	United States	99204
63	MultiCare Institute for Research & Innovation	Tacoma	Washington	United States	98405
64	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
65	Local Institution	New Lambton Heights	New South Wales	Australia	2305
66	Queensland Children's Hospital	Sth Brisbane	Queensland	Australia	4101
67	Monash Medical Centre Clayton	Clayton	Victoria	Australia	3168
68	Local Institution	Parkville	Victoria	Australia	3052
69	Local Institution	Bruxelles		Belgium	1020
70	Local Institution	Bruxelles		Belgium	1200
71	Local Institution	Edegem		Belgium	2650
72	Local Institution	Gent		Belgium	9000
73	Local Institution	Leuven		Belgium	3000
74	Alberta Children'S Hospital	Calgary	Alberta	Canada	T3B 6A8
75	Local Institution	Edmonton	Alberta	Canada	T6G 2B7
76	Local Institution	St, John's	Newfoundland and Labrador	Canada	A1B 3V6
77	Children'S Hospital London Health Sciences Centre	London	Ontario	Canada	N6A 5W9
78	Children'S Hospital Of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
79	Klinika detske onkologie	Brno		Czechia	613 00
80	Local Institution	Budapest		Hungary	1094
81	Local Institution	Debrecen		Hungary	4032
82	Local Institution	Pecs		Hungary	7623
83	Local Institution	Seoul		Korea, Republic of	03080
84	Local Institution	Seoul		Korea, Republic of	03722
85	Local Institution	Df	Distrito Federal	Mexico	04530
86	Local Institution	Guadalajara	Jalisco	Mexico	44340
87	Local Institution	Monterrey	Nuevo Leon	Mexico	64460
88	Local Institution	Christchurch		New Zealand	8011
89	Klinika Transplantacji Szpiku Onkologii i Hematologii Dzieciecej	Wroclaw		Poland	50-556
90	Oddzial Hematologii i Onkologii Dzieciecej	Zabrze		Poland	41-800
91	Local Institution	Caguas		Puerto Rico	00725
92	Local Institution	Kirov		Russian Federation	610027
93	Local Institution	Moscow		Russian Federation	115478
94	Local Institution	Moscow		Russian Federation	117198
95	Local Institution	Saint Petersburg		Russian Federation	197758
96	Local Institution	St.petersburg		Russian Federation	197341

Sponsors and Collaborators

• Bristol-Myers Squibb
• Pfizer

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Sep 3, 2020
• Statistical Analysis Plan - Mar 2, 2021

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02369653
• Other Study ID Numbers: CV185-155; 2014-000328-47
• First Posted: Feb 24, 2015
• Last Update Posted: Mar 8, 2022
• Last Verified: Feb 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Bristol-Myers Squibb: Anticoagulation
• Additional relevant MeSH terms: Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Apixaban; Anticoagulants

Study Results

Participant Flow

Pre-assignment Detail	512 participants were randomized. 256 is the number of subjects who randomized to each of Apixaban or Standard of Care arm respectively.

Arm/Group Title	Apixaban	Standard of Care
Arm/Group Description	Participants will be administered apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase. Weight range - Dose >/=35 kg - 2.5 mg twice daily <35 to 25 kg - 2 mg twice daily <25 to 18 kg - 1.5 mg twice daily <18 to 10.5 kg - 1 mg twice daily <10.5 to 6 kg - 0.5 mg twice daily	No systemic anticoagulant prophylaxis during induction chemotherapy
Period Title: Overall Study
STARTED	256	256
Adverse Event Analysis Population	250	262
COMPLETED	242	249
NOT COMPLETED	14	7

Baseline Characteristics

Arm/Group Title	Apixaban	Standard of Care	Total
Arm/Group Description	Participants will be administered apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase. Weight range - Dose >/=35 kg - 2.5 mg twice daily <35 to 25 kg - 2 mg twice daily <25 to 18 kg - 1.5 mg twice daily <18 to 10.5 kg - 1 mg twice daily <10.5 to 6 kg - 0.5 mg twice daily	No systemic anticoagulant prophylaxis during induction chemotherapy	Total of all reporting groups
Overall Participants	256	256	512
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	7.2 (4.34)	7.1 (4.39)	7.2 (4.36)
Sex: Female, Male (Count of Participants)
Female	115 44.9%	107 41.8%	222 43.4%
Male	141 55.1%	149 58.2%	290 56.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	59 23%	63 24.6%	122 23.8%
Not Hispanic or Latino	196 76.6%	192 75%	388 75.8%
Unknown or Not Reported	1 0.4%	1 0.4%	2 0.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.4%	1 0.4%	2 0.4%
Asian	25 9.8%	27 10.5%	52 10.2%
Native Hawaiian or Other Pacific Islander	1 0.4%	0 0%	1 0.2%
Black or African American	12 4.7%	12 4.7%	24 4.7%
White	194 75.8%	194 75.8%	388 75.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	23 9%	22 8.6%	45 8.8%

Outcome Measures

1. Primary Outcome

Title	The Number of Participants With Non-Fatal DVT, PE, and CVST, and VTE-Related-Death
Description	The number of participants with non-fatal deep vein thromboses (DVT) (including asymptomatic and symptomatic), pulmonary embolism (PE), cerebral venous sinus thrombosis (CVST); and venous thromboembolism (VTE) related-death objectively confirmed by a blinded, independent adjudication committee. Symptomatic events are included during the intended treatment period. Asymptomatic events are included from scans up to Day 40.
Time Frame	From first dose up to approximately 40 days after first dose

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Apixaban	Standard of Care
Arm/Group Description	Participants will be administered apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase. Weight range - Dose >/=35 kg - 2.5 mg twice daily <35 to 25 kg - 2 mg twice daily <25 to 18 kg - 1.5 mg twice daily <18 to 10.5 kg - 1 mg twice daily <10.5 to 6 kg - 0.5 mg twice daily	No systemic anticoagulant prophylaxis during induction chemotherapy
Measure Participants	256	256
Count of Participants [Participants]	31 12.1%	45 17.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Apixaban, Standard of Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0403
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

2. Primary Outcome

Title	The Number of Participants With Adjudicated Major Bleeding
Description	The number of participants with major bleeding adjudicated by a blinded, independent adjudication committee. Adjudicated 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 20g/L (ie, 2g/dL) in a 24-hour period bleeding that is retroperitoneal, pulmonary, intracranial, or otherwise involves the CNS; and/or bleeding that requires surgical intervention in an operating suite, including interventional radiology.
Time Frame	From first dose up to approximately 34 days after first dose

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Apixaban	Standard of Care
Arm/Group Description	Participants will be administered apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase. Weight range - Dose >/=35 kg - 2.5 mg twice daily <35 to 25 kg - 2 mg twice daily <25 to 18 kg - 1.5 mg twice daily <18 to 10.5 kg - 1 mg twice daily <10.5 to 6 kg - 0.5 mg twice daily	No systemic anticoagulant prophylaxis during induction chemotherapy
Measure Participants	256	256
Count of Participants [Participants]	2 0.8%	2 0.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Apixaban, Standard of Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

3. Secondary Outcome

Title	The Number of Participants With Non-fatal Asymptomatic Deep Vein Thromboses (DVT)
Description	The number of participants with non-fatal asymptomatic deep vein thromboses (DVT) adjudicated by a blinded, independent adjudication committee
Time Frame	From first dose up to approximately 40 days after first dose

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Apixaban	Standard of Care
Arm/Group Description	Participants will be administered apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase. Weight range - Dose >/=35 kg - 2.5 mg twice daily <35 to 25 kg - 2 mg twice daily <25 to 18 kg - 1.5 mg twice daily <18 to 10.5 kg - 1 mg twice daily <10.5 to 6 kg - 0.5 mg twice daily	No systemic anticoagulant prophylaxis during induction chemotherapy
Measure Participants	256	256
Count of Participants [Participants]	27 10.5%	38 14.8%

4. Secondary Outcome

Title	The Number of Participants With Non-fatal Symptomatic Deep Vein Thromboses (DVT)
Description	The number of participants with non-fatal symptomatic deep vein thromboses (DVT) adjudicated by a blinded, independent adjudication committee
Time Frame	From first dose up to approximately 34 days after first dose

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Apixaban	Standard of Care
Arm/Group Description	Participants will be administered apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase. Weight range - Dose >/=35 kg - 2.5 mg twice daily <35 to 25 kg - 2 mg twice daily <25 to 18 kg - 1.5 mg twice daily <18 to 10.5 kg - 1 mg twice daily <10.5 to 6 kg - 0.5 mg twice daily	No systemic anticoagulant prophylaxis during induction chemotherapy
Measure Participants	256	256
Count of Participants [Participants]	4 1.6%	6 2.3%

5. Secondary Outcome

Title	The Number of Participants With Non-fatal Pulmonary Embolism (PE)
Description	The number of participants with non-fatal pulmonary embolism (PE) adjudicated by a blinded, independent adjudication committee
Time Frame	From first dose up to approximately 34 days after first dose

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Apixaban	Standard of Care
Arm/Group Description	Participants will be administered apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase. Weight range - Dose >/=35 kg - 2.5 mg twice daily <35 to 25 kg - 2 mg twice daily <25 to 18 kg - 1.5 mg twice daily <18 to 10.5 kg - 1 mg twice daily <10.5 to 6 kg - 0.5 mg twice daily	No systemic anticoagulant prophylaxis during induction chemotherapy
Measure Participants	256	256
Count of Participants [Participants]	0 0%	0 0%

6. Secondary Outcome

Title	The Number of Participants With Cerebral Venous Sinus Thrombosis (CVST)
Description	The number of participants with cerebral venous sinus thrombosis (CVST) adjudicated by a blinded, independent adjudication committee
Time Frame	From first dose up to approximately 34 days after first dose

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Apixaban	Standard of Care
Arm/Group Description	Participants will be administered apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase. Weight range - Dose >/=35 kg - 2.5 mg twice daily <35 to 25 kg - 2 mg twice daily <25 to 18 kg - 1.5 mg twice daily <18 to 10.5 kg - 1 mg twice daily <10.5 to 6 kg - 0.5 mg twice daily	No systemic anticoagulant prophylaxis during induction chemotherapy
Measure Participants	256	256
Count of Participants [Participants]	0 0%	1 0.4%

7. Secondary Outcome

Title	The Number of Participants With Venous Thromboembolism (VTE)-Related-death
Description	The number of participants with venous thromboembolism (VTE)-related-death adjudicated by a blinded, independent adjudication committee
Time Frame	From first dose up to approximately 34 days after first dose

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Apixaban	Standard of Care
Arm/Group Description	Participants will be administered apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase. Weight range - Dose >/=35 kg - 2.5 mg twice daily <35 to 25 kg - 2 mg twice daily <25 to 18 kg - 1.5 mg twice daily <18 to 10.5 kg - 1 mg twice daily <10.5 to 6 kg - 0.5 mg twice daily	No systemic anticoagulant prophylaxis during induction chemotherapy
Measure Participants	256	256
Count of Participants [Participants]	0 0%	0 0%

8. Secondary Outcome

Title	The Number of Participants With Major and Clinically Relevant Non-Major Bleeding (CRNMB)
Description	The number of participants with major and clinically relevant non-major bleeding (CRNMB) adjudicated by a blinded, independent adjudication committee CRNM bleeding is defined as bleeding that satisfies one or both of the following: overt bleeding for which blood product is administered and not directly attributable to the subject's underlying medical condition and bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating room
Time Frame	From first dose up to approximately 34 days after first dose

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Apixaban	Standard of Care
Arm/Group Description	Participants will be administered apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase. Weight range - Dose >/=35 kg - 2.5 mg twice daily <35 to 25 kg - 2 mg twice daily <25 to 18 kg - 1.5 mg twice daily <18 to 10.5 kg - 1 mg twice daily <10.5 to 6 kg - 0.5 mg twice daily	No systemic anticoagulant prophylaxis during induction chemotherapy
Measure Participants	256	256
Count of Participants [Participants]	13 5.1%	5 2%

9. Secondary Outcome

Title	The Number of Participant Deaths
Description	The number of participant deaths adjudicated by a blinded, independent adjudication committee
Time Frame	From first dose date until the end of the treatment period + 30 days (Up to approximately 59 days)

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Apixaban	Standard of Care
Arm/Group Description	Participants will be administered apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase. Weight range - Dose >/=35 kg - 2.5 mg twice daily <35 to 25 kg - 2 mg twice daily <25 to 18 kg - 1.5 mg twice daily <18 to 10.5 kg - 1 mg twice daily <10.5 to 6 kg - 0.5 mg twice daily	No systemic anticoagulant prophylaxis during induction chemotherapy
Measure Participants	256	256
Count of Participants [Participants]	1 0.4%	3 1.2%

10. Secondary Outcome

Title	The Number of Participants With an Arterial Thromboembolic Event
Description	The number of participants with an arterial thromboembolic event including paradoxical embolism and stroke adjudicated by a blinded, independent adjudication committee
Time Frame	From first dose up to approximately 34 days after first dose

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Apixaban	Standard of Care
Arm/Group Description	Participants will be administered apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase. Weight range - Dose >/=35 kg - 2.5 mg twice daily <35 to 25 kg - 2 mg twice daily <25 to 18 kg - 1.5 mg twice daily <18 to 10.5 kg - 1 mg twice daily <10.5 to 6 kg - 0.5 mg twice daily	No systemic anticoagulant prophylaxis during induction chemotherapy
Measure Participants	256	256
Count of Participants [Participants]	0 0%	0 0%

11. Secondary Outcome

Title	The Number of Participants With a CVAD-Related Infection
Description	The number of participants with a central venous access device (CVAD)-related infection adjudicated by a blinded, independent adjudication committee
Time Frame	From first dose up to approximately 34 days after first dose

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Apixaban	Standard of Care
Arm/Group Description	Participants will be administered apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase. Weight range - Dose >/=35 kg - 2.5 mg twice daily <35 to 25 kg - 2 mg twice daily <25 to 18 kg - 1.5 mg twice daily <18 to 10.5 kg - 1 mg twice daily <10.5 to 6 kg - 0.5 mg twice daily	No systemic anticoagulant prophylaxis during induction chemotherapy
Measure Participants	256	256
Count of Participants [Participants]	1 0.4%	6 2.3%

12. Secondary Outcome

Title	The Number of Participants Needing Catheter Replacements During the Study
Description	The number of participants needing catheter replacements during the study
Time Frame	From first dose up to approximately 34 days after first dose

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Apixaban	Standard of Care
Arm/Group Description	Participants will be administered apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase. Weight range - Dose >/=35 kg - 2.5 mg twice daily <35 to 25 kg - 2 mg twice daily <25 to 18 kg - 1.5 mg twice daily <18 to 10.5 kg - 1 mg twice daily <10.5 to 6 kg - 0.5 mg twice daily	No systemic anticoagulant prophylaxis during induction chemotherapy
Measure Participants	256	256
Count of Participants [Participants]	3 1.2%	2 0.8%

13. Secondary Outcome

Title	The Number of Participants With CVAD Patency Restoration Events After Thrombolytic Therapy Use
Description	The number of participants with central venous access device (CVAD) patency restoration events after thrombolytic therapy use
Time Frame	From first dose up to approximately 34 days after first dose

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Apixaban	Standard of Care
Arm/Group Description	Participants will be administered apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase. Weight range - Dose >/=35 kg - 2.5 mg twice daily <35 to 25 kg - 2 mg twice daily <25 to 18 kg - 1.5 mg twice daily <18 to 10.5 kg - 1 mg twice daily <10.5 to 6 kg - 0.5 mg twice daily	No systemic anticoagulant prophylaxis during induction chemotherapy
Measure Participants	256	256
Count of Participants [Participants]	0 0%	0 0%

14. Secondary Outcome

Title	The Number Participants Experiencing Superficial Vein Thrombosis Events
Description	The number participants experiencing superficial vein thrombosis events. Clots that occur in a superficial vein ie, cephalic vein, basilic vein (upper extremity) or saphenous vein (lower extremity) confirmed by radiographic imaging.
Time Frame	From first dose up to approximately 34 days after first dose

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Apixaban	Standard of Care
Arm/Group Description	Participants will be administered apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase. Weight range - Dose >/=35 kg - 2.5 mg twice daily <35 to 25 kg - 2 mg twice daily <25 to 18 kg - 1.5 mg twice daily <18 to 10.5 kg - 1 mg twice daily <10.5 to 6 kg - 0.5 mg twice daily	No systemic anticoagulant prophylaxis during induction chemotherapy
Measure Participants	256	256
Count of Participants [Participants]	4 1.6%	2 0.8%

15. Secondary Outcome

Title	The Number of Participants With Clinically Relevant Non-Major Bleeding Events (CRNMB)
Description	The number of participants with clinically relevant non-major bleeding events (CRNMB) adjudicated by a blinded, independent adjudication committee. CRNM bleeding is defined as bleeding that satisfies one or both of the following: overt bleeding for which blood product is administered and not directly attributable to the subject's underlying medical condition and bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating room
Time Frame	From first dose up to approximately 34 days after first dose

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Apixaban	Standard of Care
Arm/Group Description	Participants will be administered apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase. Weight range - Dose >/=35 kg - 2.5 mg twice daily <35 to 25 kg - 2 mg twice daily <25 to 18 kg - 1.5 mg twice daily <18 to 10.5 kg - 1 mg twice daily <10.5 to 6 kg - 0.5 mg twice daily	No systemic anticoagulant prophylaxis during induction chemotherapy
Measure Participants	256	256
Count of Participants [Participants]	11 4.3%	3 1.2%

16. Secondary Outcome

Title	The Number of Participants With Minor Bleeding Events
Description	The number of participants with minor bleeding events adjudicated by a blinded, independent adjudication committee. Minor bleeding defined as any overt or macroscopic evidence of bleeding that does not fulfill the criteria for either major bleeding or CRNMB
Time Frame	From first dose up to approximately 34 days after first dose

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Apixaban	Standard of Care
Arm/Group Description	Participants will be administered apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase. Weight range - Dose >/=35 kg - 2.5 mg twice daily <35 to 25 kg - 2 mg twice daily <25 to 18 kg - 1.5 mg twice daily <18 to 10.5 kg - 1 mg twice daily <10.5 to 6 kg - 0.5 mg twice daily	No systemic anticoagulant prophylaxis during induction chemotherapy
Measure Participants	256	256
Count of Participants [Participants]	37 14.5%	20 7.8%

17. Secondary Outcome

Title	The Number of Platelet Transfusions Needed During the Study
Description	The number of platelet transfusions needed during the study. The events are not adjudicated. A subject could have more than one platelet transfusion.
Time Frame	From first dose up to approximately 34 days after first dose

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Apixaban	Standard of Care
Arm/Group Description	Participants will be administered apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase. Weight range - Dose >/=35 kg - 2.5 mg twice daily <35 to 25 kg - 2 mg twice daily <25 to 18 kg - 1.5 mg twice daily <18 to 10.5 kg - 1 mg twice daily <10.5 to 6 kg - 0.5 mg twice daily	No systemic anticoagulant prophylaxis during induction chemotherapy
Measure Participants	256	256
Number [Platelet Transfusions]	266	248

18. Secondary Outcome

Title	Maximum Observed Concentration (Cmax)
Description	The maximum observed concentration (Cmax) was measured to assess the pharmacokinetics of oral or enteric apixaban in pediatric subjects receiving induction chemotherapy.
Time Frame	pre-dose, 1-4 hours post dose

Outcome Measure Data

Analysis Population Description

All randomized participants in the apixaban arm with available pharmacokinetic data

Arm/Group Title	Participants Weight Range ≥ 35 kg	Participants Weight Range 25 to < 35 kg	Participants Weight Range 18 to < 25 kg	Participants Weight Range 10.5 to < 18 kg
Arm/Group Description	Participants will be administered 2.5mg apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase	Participants will be administered 2mg apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase	Participants will be administered 1.5mg apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase	Participants will be administered 1mg apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase
Measure Participants	71	30	50	73
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	56.5 (36.5)	63.6 (38.6)	61.4 (43.9)	54.2 (46.8)

19. Secondary Outcome

Title	Trough Observed Concentration (Cmin)
Description	The trough observed concentration (Cmin) was measured to assess the pharmacokinetics of oral or enteric apixaban in pediatric subjects receiving induction chemotherapy.
Time Frame	pre-dose, 1-4 hours post dose

Outcome Measure Data

Analysis Population Description

All randomized participants in the apixaban arm with available pharmacokinetic data

Arm/Group Title	Participants Weight Range ≥ 35 kg	Participants Weight Range 25 to < 35 kg	Participants Weight Range 18 to < 25 kg	Participants Weight Range 10.5 to < 18 kg
Arm/Group Description	Participants will be administered 2.5mg apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase	Participants will be administered 2mg apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase	Participants will be administered 1.5mg apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase	Participants will be administered 1mg apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase
Measure Participants	71	30	50	73
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	18.8 (57.8)	18.1 (97.4)	12 (142)	12.9 (113)

20. Secondary Outcome

Title	Area Under the Concentration-Time Curve [AUC(TAU)]
Description	The area under the concentration-time curve [AUC(TAU)] was measured to assess the pharmacokinetics of oral or enteric apixaban in pediatric subjects receiving induction chemotherapy.
Time Frame	pre-dose, 1-4 hours post dose

Outcome Measure Data

Analysis Population Description

All randomized participants in the apixaban arm with available pharmacokinetic data

Arm/Group Title	Participants Weight Range ≥ 35 kg	Participants Weight Range 25 to < 35 kg	Participants Weight Range 18 to < 25 kg	Participants Weight Range 10.5 to < 18 kg
Arm/Group Description	Participants will be administered 2.5mg apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase	Participants will be administered 2mg apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase	Participants will be administered 1.5mg apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase	Participants will be administered 1mg apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase
Measure Participants	71	30	50	73
Geometric Mean (Geometric Coefficient of Variation) [ng•h/mL]	470 (35.3)	510 (42.7)	453 (44.8)	416 (48.5)

21. Secondary Outcome

Title	Anti-FXa Activity
Description	Anti-FXa Activity was measured to characterize the relationship between apixaban plasma concentration and anti-FXa activity in pediatric subjects receiving induction chemotherapy
Time Frame	pre-dose and 2.5 hours after dosing on day 7. Day 8 and day 15.

Outcome Measure Data

Analysis Population Description

All randomized participants in the apixaban arm with available pharmacodynamic data

Arm/Group Title	Participants Weight Range ≥ 35 kg	Participants Weight Range 25 to < 35 kg	Participants Weight Range 18 to < 25 kg	Participants Weight Range 10.5 to < 18 kg
Arm/Group Description	Participants will be administered 2.5mg apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase	Participants will be administered 2mg apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase	Participants will be administered 1.5mg apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase	Participants will be administered 1mg apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase
Measure Participants	28	14	21	31
Day 7 (Predose)	55.3 (16.4)	62.2 (19.4)	52.8 (16)	44.2 (12.9)
Day 7 (2.5 hours)	78.7 (28.8)	72.1 (30.6)	77.5 (30.8)	87.5 (45.5)
Day 8	55.2 (8.96)	47.5 (10.6)	48 (11.3)
Day 15	70.2 (28)	75.3 (33.9)	63.9 (21.6)	64.8 (25.3)

Adverse Events

Time Frame	AEs are collected from the first dose date until the end of the treatment period + 2 days (Up to approximately 31 days) SAEs are collected from the first dose date until the end of the treatment period + 30 days (Up to approximately 59 days). All Cause Mortality was collected from first dose up to DBL date: Sep-13-2021 (up to approximately 6 years.)
Arm/Group Title	Apixaban		Standard of Care
Arm/Group Description	Participants will be administered apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase		No systemic anticoagulant prophylaxis during induction chemotherapy
All Cause Mortality
	Apixaban		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/250 (0.4%)		4/262 (1.5%)
Serious Adverse Events
	Apixaban		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	91/250 (36.4%)		83/262 (31.7%)
Blood and lymphatic system disorders
Anaemia	0/250 (0%)		3/262 (1.1%)
Coagulopathy	1/250 (0.4%)		1/262 (0.4%)
Febrile bone marrow aplasia	1/250 (0.4%)		0/262 (0%)
Febrile neutropenia	15/250 (6%)		16/262 (6.1%)
Neutropenia	0/250 (0%)		3/262 (1.1%)
Cardiac disorders
Cardiac arrest	1/250 (0.4%)		1/262 (0.4%)
Intracardiac thrombus	1/250 (0.4%)		0/262 (0%)
Pneumopericardium	0/250 (0%)		1/262 (0.4%)
Tachycardia	0/250 (0%)		1/262 (0.4%)
Endocrine disorders
Adrenal insufficiency	1/250 (0.4%)		0/262 (0%)
Inappropriate antidiuretic hormone secretion	0/250 (0%)		1/262 (0.4%)
Eye disorders
Ocular hypertension	1/250 (0.4%)		0/262 (0%)
Gastrointestinal disorders
Abdominal pain	1/250 (0.4%)		3/262 (1.1%)
Colitis	2/250 (0.8%)		5/262 (1.9%)
Constipation	1/250 (0.4%)		5/262 (1.9%)
Haematochezia	1/250 (0.4%)		0/262 (0%)
Ileus	1/250 (0.4%)		1/262 (0.4%)
Nausea	1/250 (0.4%)		3/262 (1.1%)
Oesophagitis	1/250 (0.4%)		0/262 (0%)
Pancreatitis	2/250 (0.8%)		3/262 (1.1%)
Pancreatitis acute	1/250 (0.4%)		1/262 (0.4%)
Pneumatosis intestinalis	1/250 (0.4%)		0/262 (0%)
Pneumoperitoneum	1/250 (0.4%)		0/262 (0%)
Proctitis	0/250 (0%)		1/262 (0.4%)
Small intestinal obstruction	0/250 (0%)		1/262 (0.4%)
Stomatitis	0/250 (0%)		1/262 (0.4%)
Vomiting	1/250 (0.4%)		1/262 (0.4%)
General disorders
Device related thrombosis	1/250 (0.4%)		0/262 (0%)
Mucosal inflammation	2/250 (0.8%)		0/262 (0%)
Non-cardiac chest pain	1/250 (0.4%)		0/262 (0%)
Pain	0/250 (0%)		1/262 (0.4%)
Pyrexia	7/250 (2.8%)		7/262 (2.7%)
Hepatobiliary disorders
Acute hepatic failure	0/250 (0%)		1/262 (0.4%)
Cholelithiasis	1/250 (0.4%)		0/262 (0%)
Drug-induced liver injury	1/250 (0.4%)		0/262 (0%)
Hyperbilirubinaemia	1/250 (0.4%)		0/262 (0%)
Immune system disorders
Anaphylactic reaction	0/250 (0%)		2/262 (0.8%)
Hypersensitivity	1/250 (0.4%)		0/262 (0%)
Infections and infestations
Appendicitis	1/250 (0.4%)		2/262 (0.8%)
Aspergillus infection	1/250 (0.4%)		0/262 (0%)
Bacteraemia	1/250 (0.4%)		0/262 (0%)
Bacterial infection	0/250 (0%)		1/262 (0.4%)
COVID-19	0/250 (0%)		1/262 (0.4%)
Clostridium difficile infection	0/250 (0%)		1/262 (0.4%)
Cytomegalovirus infection	0/250 (0%)		1/262 (0.4%)
Device related infection	3/250 (1.2%)		2/262 (0.8%)
Enterocolitis infectious	1/250 (0.4%)		0/262 (0%)
Escherichia bacteraemia	1/250 (0.4%)		0/262 (0%)
Escherichia infection	1/250 (0.4%)		0/262 (0%)
Fungal sepsis	1/250 (0.4%)		0/262 (0%)
Gastroenteritis norovirus	0/250 (0%)		1/262 (0.4%)
Haemophilus bacteraemia	1/250 (0.4%)		0/262 (0%)
Infective thrombosis	1/250 (0.4%)		0/262 (0%)
Meningitis	2/250 (0.8%)		0/262 (0%)
Osteomyelitis	1/250 (0.4%)		0/262 (0%)
Pneumonia	1/250 (0.4%)		3/262 (1.1%)
Postoperative wound infection	0/250 (0%)		1/262 (0.4%)
Sepsis	6/250 (2.4%)		5/262 (1.9%)
Septic shock	0/250 (0%)		1/262 (0.4%)
Sinusitis	1/250 (0.4%)		1/262 (0.4%)
Soft tissue infection	0/250 (0%)		1/262 (0.4%)
Staphylococcal bacteraemia	1/250 (0.4%)		0/262 (0%)
Staphylococcal infection	0/250 (0%)		1/262 (0.4%)
Stomatococcal infection	0/250 (0%)		1/262 (0.4%)
Streptococcal sepsis	1/250 (0.4%)		0/262 (0%)
Upper respiratory tract infection	1/250 (0.4%)		0/262 (0%)
Injury, poisoning and procedural complications
Epidural haemorrhage	1/250 (0.4%)		0/262 (0%)
Meningitis chemical	1/250 (0.4%)		0/262 (0%)
Post lumbar puncture syndrome	1/250 (0.4%)		0/262 (0%)
Procedural pain	0/250 (0%)		1/262 (0.4%)
Vascular access complication	1/250 (0.4%)		2/262 (0.8%)
Investigations
Alanine aminotransferase increased	1/250 (0.4%)		0/262 (0%)
Aspartate aminotransferase increased	1/250 (0.4%)		0/262 (0%)
Hepatic enzyme increased	1/250 (0.4%)		0/262 (0%)
Human rhinovirus test positive	1/250 (0.4%)		0/262 (0%)
Lipase increased	1/250 (0.4%)		0/262 (0%)
Liver function test abnormal	1/250 (0.4%)		0/262 (0%)
Platelet count decreased	1/250 (0.4%)		0/262 (0%)
Transaminases increased	0/250 (0%)		1/262 (0.4%)
Metabolism and nutrition disorders
Decreased appetite	3/250 (1.2%)		0/262 (0%)
Dehydration	1/250 (0.4%)		4/262 (1.5%)
Diabetic ketoacidosis	1/250 (0.4%)		0/262 (0%)
Hyperglycaemia	4/250 (1.6%)		2/262 (0.8%)
Hyperlipidaemia	1/250 (0.4%)		0/262 (0%)
Hypokalaemia	1/250 (0.4%)		0/262 (0%)
Hyponatraemia	1/250 (0.4%)		1/262 (0.4%)
Musculoskeletal and connective tissue disorders
Bone pain	0/250 (0%)		1/262 (0.4%)
Nervous system disorders
Cerebral venous sinus thrombosis	0/250 (0%)		3/262 (1.1%)
Encephalopathy	0/250 (0%)		2/262 (0.8%)
Guillain-Barre syndrome	0/250 (0%)		1/262 (0.4%)
Haemorrhage intracranial	0/250 (0%)		1/262 (0.4%)
Headache	1/250 (0.4%)		0/262 (0%)
Leukoencephalopathy	2/250 (0.8%)		0/262 (0%)
Neuropathy peripheral	1/250 (0.4%)		0/262 (0%)
Peripheral motor neuropathy	0/250 (0%)		1/262 (0.4%)
Posterior reversible encephalopathy syndrome	0/250 (0%)		2/262 (0.8%)
Seizure	2/250 (0.8%)		2/262 (0.8%)
Syncope	0/250 (0%)		1/262 (0.4%)
Psychiatric disorders
Anxiety	0/250 (0%)		1/262 (0.4%)
Psychotic disorder	1/250 (0.4%)		0/262 (0%)
Renal and urinary disorders
Acute kidney injury	1/250 (0.4%)		0/262 (0%)
Haematuria	1/250 (0.4%)		0/262 (0%)
Nephrolithiasis	2/250 (0.8%)		0/262 (0%)
Urinary retention	0/250 (0%)		1/262 (0.4%)
Reproductive system and breast disorders
Heavy menstrual bleeding	0/250 (0%)		1/262 (0.4%)
Testicular cyst	0/250 (0%)		1/262 (0.4%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	0/250 (0%)		1/262 (0.4%)
Pneumonitis	2/250 (0.8%)		0/262 (0%)
Pneumothorax	2/250 (0.8%)		1/262 (0.4%)
Respiratory failure	0/250 (0%)		1/262 (0.4%)
Vascular disorders
Deep vein thrombosis	2/250 (0.8%)		6/262 (2.3%)
Embolism	9/250 (3.6%)		3/262 (1.1%)
Hypertension	3/250 (1.2%)		0/262 (0%)
Hypotension	1/250 (0.4%)		0/262 (0%)
Jugular vein thrombosis	1/250 (0.4%)		2/262 (0.8%)
Subclavian vein thrombosis	0/250 (0%)		1/262 (0.4%)
Thrombosis	2/250 (0.8%)		1/262 (0.4%)
Venous thrombosis	1/250 (0.4%)		0/262 (0%)
Other (Not Including Serious) Adverse Events
	Apixaban		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	204/250 (81.6%)		193/262 (73.7%)
Blood and lymphatic system disorders
Anaemia	85/250 (34%)		88/262 (33.6%)
Febrile neutropenia	14/250 (5.6%)		7/262 (2.7%)
Neutropenia	17/250 (6.8%)		15/262 (5.7%)
Thrombocytopenia	28/250 (11.2%)		25/262 (9.5%)
Cardiac disorders
Tachycardia	15/250 (6%)		13/262 (5%)
Gastrointestinal disorders
Abdominal distension	17/250 (6.8%)		12/262 (4.6%)
Abdominal pain	34/250 (13.6%)		48/262 (18.3%)
Constipation	58/250 (23.2%)		50/262 (19.1%)
Diarrhoea	26/250 (10.4%)		16/262 (6.1%)
Nausea	16/250 (6.4%)		20/262 (7.6%)
Stomatitis	12/250 (4.8%)		15/262 (5.7%)
Vomiting	18/250 (7.2%)		17/262 (6.5%)
General disorders
Fatigue	14/250 (5.6%)		20/262 (7.6%)
Pyrexia	13/250 (5.2%)		11/262 (4.2%)
Investigations
Alanine aminotransferase increased	46/250 (18.4%)		39/262 (14.9%)
Aspartate aminotransferase increased	28/250 (11.2%)		18/262 (6.9%)
Blood bilirubin increased	17/250 (6.8%)		16/262 (6.1%)
Neutrophil count decreased	22/250 (8.8%)		26/262 (9.9%)
Platelet count decreased	54/250 (21.6%)		55/262 (21%)
White blood cell count decreased	21/250 (8.4%)		28/262 (10.7%)
Metabolism and nutrition disorders
Hyperglycaemia	19/250 (7.6%)		30/262 (11.5%)
Hypoalbuminaemia	29/250 (11.6%)		34/262 (13%)
Hypocalcaemia	12/250 (4.8%)		21/262 (8%)
Hyponatraemia	36/250 (14.4%)		30/262 (11.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	12/250 (4.8%)		14/262 (5.3%)
Back pain	29/250 (11.6%)		19/262 (7.3%)
Muscular weakness	9/250 (3.6%)		14/262 (5.3%)
Pain in extremity	28/250 (11.2%)		25/262 (9.5%)
Pain in jaw	14/250 (5.6%)		15/262 (5.7%)
Nervous system disorders
Headache	16/250 (6.4%)		20/262 (7.6%)
Respiratory, thoracic and mediastinal disorders
Cough	16/250 (6.4%)		12/262 (4.6%)
Epistaxis	24/250 (9.6%)		14/262 (5.3%)
Vascular disorders
Hypertension	23/250 (9.2%)		26/262 (9.9%)

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.