Trial Outcomes & Findings for 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 (NCT NCT02369653)

Last Updated: 2022-03-08

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

512 participants

Primary outcome timeframe

From first dose up to approximately 40 days after first dose

Results posted on

2022-03-08

Participant Flow

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

Participant milestones

Participant milestones
Measure	Apixaban 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	Standard of Care No systemic anticoagulant prophylaxis during induction chemotherapy
Overall Study STARTED	256	256
Overall Study Adverse Event Analysis Population	250	262
Overall Study COMPLETED	242	249
Overall Study NOT COMPLETED	14	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Apixaban 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	Standard of Care No systemic anticoagulant prophylaxis during induction chemotherapy
Overall Study Lost to Follow-up	0	1
Overall Study Administrative reason by sponsor	0	1
Overall Study Death	1	2
Overall Study Participant withdrew consent	13	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Apixaban n=256 Participants 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	Standard of Care n=256 Participants No systemic anticoagulant prophylaxis during induction chemotherapy	Total n=512 Participants Total of all reporting groups
Age, Continuous	7.2 Years STANDARD_DEVIATION 4.34 • n=5 Participants	7.1 Years STANDARD_DEVIATION 4.39 • n=7 Participants	7.2 Years STANDARD_DEVIATION 4.36 • n=5 Participants
Sex: Female, Male Female	115 Participants n=5 Participants	107 Participants n=7 Participants	222 Participants n=5 Participants
Sex: Female, Male Male	141 Participants n=5 Participants	149 Participants n=7 Participants	290 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	59 Participants n=5 Participants	63 Participants n=7 Participants	122 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	196 Participants n=5 Participants	192 Participants n=7 Participants	388 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	25 Participants n=5 Participants	27 Participants n=7 Participants	52 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Race (NIH/OMB) White	194 Participants n=5 Participants	194 Participants n=7 Participants	388 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	23 Participants n=5 Participants	22 Participants n=7 Participants	45 Participants n=5 Participants

PRIMARY outcome

Timeframe: From first dose up to approximately 40 days after first dose

Population: All randomized participants

Outcome measures

Outcome measures
Measure	Apixaban n=256 Participants 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	Standard of Care n=256 Participants No systemic anticoagulant prophylaxis during induction chemotherapy	Participants Weight Range 18 to < 25 kg 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 Weight Range 10.5 to < 18 kg 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
The Number of Participants With Non-Fatal DVT, PE, and CVST, and VTE-Related-Death	31 Participants	45 Participants	—	—

PRIMARY outcome

Timeframe: From first dose up to approximately 34 days after first dose

Population: Safety Population

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: 1. fatal bleeding 2. clinically overt bleeding associated with a decrease in hemoglobin of at least 20g/L (ie, 2g/dL) in a 24-hour period 3. bleeding that is retroperitoneal, pulmonary, intracranial, or otherwise involves the CNS; and/or 4. bleeding that requires surgical intervention in an operating suite, including interventional radiology.

Outcome measures

Outcome measures
Measure	Apixaban n=256 Participants 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	Standard of Care n=256 Participants No systemic anticoagulant prophylaxis during induction chemotherapy	Participants Weight Range 18 to < 25 kg 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 Weight Range 10.5 to < 18 kg 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
The Number of Participants With Adjudicated Major Bleeding	2 Participants	2 Participants	—	—

SECONDARY outcome

Timeframe: From first dose up to approximately 40 days after first dose

Population: All randomized participants

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

Outcome measures

Outcome measures
Measure	Apixaban n=256 Participants 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	Standard of Care n=256 Participants No systemic anticoagulant prophylaxis during induction chemotherapy	Participants Weight Range 18 to < 25 kg 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 Weight Range 10.5 to < 18 kg 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
The Number of Participants With Non-fatal Asymptomatic Deep Vein Thromboses (DVT)	27 Participants	38 Participants	—	—

SECONDARY outcome

Timeframe: From first dose up to approximately 34 days after first dose

Population: All randomized participants

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

Outcome measures

Outcome measures
Measure	Apixaban n=256 Participants 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	Standard of Care n=256 Participants No systemic anticoagulant prophylaxis during induction chemotherapy	Participants Weight Range 18 to < 25 kg 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 Weight Range 10.5 to < 18 kg 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
The Number of Participants With Non-fatal Symptomatic Deep Vein Thromboses (DVT)	4 Participants	6 Participants	—	—

SECONDARY outcome

Timeframe: From first dose up to approximately 34 days after first dose

Population: All randomized participants

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

Outcome measures

Outcome measures
Measure	Apixaban n=256 Participants 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	Standard of Care n=256 Participants No systemic anticoagulant prophylaxis during induction chemotherapy	Participants Weight Range 18 to < 25 kg 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 Weight Range 10.5 to < 18 kg 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
The Number of Participants With Non-fatal Pulmonary Embolism (PE)	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: From first dose up to approximately 34 days after first dose

Population: All randomized participants

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

Outcome measures

Outcome measures
Measure	Apixaban n=256 Participants 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	Standard of Care n=256 Participants No systemic anticoagulant prophylaxis during induction chemotherapy	Participants Weight Range 18 to < 25 kg 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 Weight Range 10.5 to < 18 kg 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
The Number of Participants With Cerebral Venous Sinus Thrombosis (CVST)	0 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: From first dose up to approximately 34 days after first dose

Population: All randomized participants

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

Outcome measures

Outcome measures
Measure	Apixaban n=256 Participants 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	Standard of Care n=256 Participants No systemic anticoagulant prophylaxis during induction chemotherapy	Participants Weight Range 18 to < 25 kg 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 Weight Range 10.5 to < 18 kg 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
The Number of Participants With Venous Thromboembolism (VTE)-Related-death	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: From first dose up to approximately 34 days after first dose

Population: Safety Population

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: 1. overt bleeding for which blood product is administered and not directly attributable to the subject's underlying medical condition and 2. bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating room

Outcome measures

Outcome measures
Measure	Apixaban n=256 Participants 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	Standard of Care n=256 Participants No systemic anticoagulant prophylaxis during induction chemotherapy	Participants Weight Range 18 to < 25 kg 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 Weight Range 10.5 to < 18 kg 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
The Number of Participants With Major and Clinically Relevant Non-Major Bleeding (CRNMB)	13 Participants	5 Participants	—	—

SECONDARY outcome

Timeframe: From first dose date until the end of the treatment period + 30 days (Up to approximately 59 days)

Population: All randomized participants

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

Outcome measures

Outcome measures
Measure	Apixaban n=256 Participants 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	Standard of Care n=256 Participants No systemic anticoagulant prophylaxis during induction chemotherapy	Participants Weight Range 18 to < 25 kg 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 Weight Range 10.5 to < 18 kg 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
The Number of Participant Deaths	1 Participants	3 Participants	—	—

SECONDARY outcome

Timeframe: From first dose up to approximately 34 days after first dose

Population: All randomized participants

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

Outcome measures

Outcome measures
Measure	Apixaban n=256 Participants 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	Standard of Care n=256 Participants No systemic anticoagulant prophylaxis during induction chemotherapy	Participants Weight Range 18 to < 25 kg 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 Weight Range 10.5 to < 18 kg 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
The Number of Participants With an Arterial Thromboembolic Event	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: From first dose up to approximately 34 days after first dose

Population: All randomized participants

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

Outcome measures

Outcome measures
Measure	Apixaban n=256 Participants 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	Standard of Care n=256 Participants No systemic anticoagulant prophylaxis during induction chemotherapy	Participants Weight Range 18 to < 25 kg 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 Weight Range 10.5 to < 18 kg 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
The Number of Participants With a CVAD-Related Infection	1 Participants	6 Participants	—	—

SECONDARY outcome

Timeframe: From first dose up to approximately 34 days after first dose

Population: All randomized participants

The number of participants needing catheter replacements during the study

Outcome measures

Outcome measures
Measure	Apixaban n=256 Participants 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	Standard of Care n=256 Participants No systemic anticoagulant prophylaxis during induction chemotherapy	Participants Weight Range 18 to < 25 kg 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 Weight Range 10.5 to < 18 kg 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
The Number of Participants Needing Catheter Replacements During the Study	3 Participants	2 Participants	—	—

SECONDARY outcome

Timeframe: From first dose up to approximately 34 days after first dose

Population: All randomized participants

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

Outcome measures

Outcome measures
Measure	Apixaban n=256 Participants 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	Standard of Care n=256 Participants No systemic anticoagulant prophylaxis during induction chemotherapy	Participants Weight Range 18 to < 25 kg 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 Weight Range 10.5 to < 18 kg 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
The Number of Participants With CVAD Patency Restoration Events After Thrombolytic Therapy Use	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: From first dose up to approximately 34 days after first dose

Population: All randomized participants

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.

Outcome measures

Outcome measures
Measure	Apixaban n=256 Participants 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	Standard of Care n=256 Participants No systemic anticoagulant prophylaxis during induction chemotherapy	Participants Weight Range 18 to < 25 kg 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 Weight Range 10.5 to < 18 kg 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
The Number Participants Experiencing Superficial Vein Thrombosis Events	4 Participants	2 Participants	—	—

SECONDARY outcome

Timeframe: From first dose up to approximately 34 days after first dose

Population: All randomized participants

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: 1. overt bleeding for which blood product is administered and not directly attributable to the subject's underlying medical condition and 2. bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating room

Outcome measures

Outcome measures
Measure	Apixaban n=256 Participants 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	Standard of Care n=256 Participants No systemic anticoagulant prophylaxis during induction chemotherapy	Participants Weight Range 18 to < 25 kg 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 Weight Range 10.5 to < 18 kg 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
The Number of Participants With Clinically Relevant Non-Major Bleeding Events (CRNMB)	11 Participants	3 Participants	—	—

SECONDARY outcome

Timeframe: From first dose up to approximately 34 days after first dose

Population: All randomized participants

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

Outcome measures

Outcome measures
Measure	Apixaban n=256 Participants 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	Standard of Care n=256 Participants No systemic anticoagulant prophylaxis during induction chemotherapy	Participants Weight Range 18 to < 25 kg 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 Weight Range 10.5 to < 18 kg 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
The Number of Participants With Minor Bleeding Events	37 Participants	20 Participants	—	—

SECONDARY outcome

Timeframe: From first dose up to approximately 34 days after first dose

Population: All randomized participants

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

Outcome measures

Outcome measures
Measure	Apixaban n=256 Participants 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	Standard of Care n=256 Participants No systemic anticoagulant prophylaxis during induction chemotherapy	Participants Weight Range 18 to < 25 kg 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 Weight Range 10.5 to < 18 kg 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
The Number of Platelet Transfusions Needed During the Study	266 Platelet Transfusions	248 Platelet Transfusions	—	—

SECONDARY outcome

Timeframe: pre-dose, 1-4 hours post dose

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

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

Outcome measures

Outcome measures
Measure	Apixaban n=71 Participants 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	Standard of Care n=30 Participants No systemic anticoagulant prophylaxis during induction chemotherapy	Participants Weight Range 18 to < 25 kg n=50 Participants 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 Weight Range 10.5 to < 18 kg n=73 Participants 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
Maximum Observed Concentration (Cmax)	56.5 ng/mL Geometric Coefficient of Variation 36.5	63.6 ng/mL Geometric Coefficient of Variation 38.6	61.4 ng/mL Geometric Coefficient of Variation 43.9	54.2 ng/mL Geometric Coefficient of Variation 46.8

SECONDARY outcome

Timeframe: pre-dose, 1-4 hours post dose

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

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

Outcome measures

Outcome measures
Measure	Apixaban n=71 Participants 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	Standard of Care n=30 Participants No systemic anticoagulant prophylaxis during induction chemotherapy	Participants Weight Range 18 to < 25 kg n=50 Participants 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 Weight Range 10.5 to < 18 kg n=73 Participants 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
Trough Observed Concentration (Cmin)	18.8 ng/mL Geometric Coefficient of Variation 57.8	18.1 ng/mL Geometric Coefficient of Variation 97.4	12 ng/mL Geometric Coefficient of Variation 142	12.9 ng/mL Geometric Coefficient of Variation 113

SECONDARY outcome

Timeframe: pre-dose, 1-4 hours post dose

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

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.

Outcome measures

Outcome measures
Measure	Apixaban n=71 Participants 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	Standard of Care n=30 Participants No systemic anticoagulant prophylaxis during induction chemotherapy	Participants Weight Range 18 to < 25 kg n=50 Participants 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 Weight Range 10.5 to < 18 kg n=73 Participants 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
Area Under the Concentration-Time Curve [AUC(TAU)]	470 ng•h/mL Geometric Coefficient of Variation 35.3	510 ng•h/mL Geometric Coefficient of Variation 42.7	453 ng•h/mL Geometric Coefficient of Variation 44.8	416 ng•h/mL Geometric Coefficient of Variation 48.5

SECONDARY outcome

Timeframe: pre-dose and 2.5 hours after dosing on day 7. Day 8 and day 15.

Population: All randomized participants in the apixaban arm with available pharmacodynamic data

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

Outcome measures

Outcome measures
Measure	Apixaban n=28 Participants 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	Standard of Care n=14 Participants No systemic anticoagulant prophylaxis during induction chemotherapy	Participants Weight Range 18 to < 25 kg n=21 Participants 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 Weight Range 10.5 to < 18 kg n=31 Participants 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
Anti-FXa Activity Day 7 (Predose)	55.3 Anti-FXa activity (ng/mL) Standard Deviation 16.4	62.2 Anti-FXa activity (ng/mL) Standard Deviation 19.4	52.8 Anti-FXa activity (ng/mL) Standard Deviation 16	44.2 Anti-FXa activity (ng/mL) Standard Deviation 12.9
Anti-FXa Activity Day 7 (2.5 hours)	78.7 Anti-FXa activity (ng/mL) Standard Deviation 28.8	72.1 Anti-FXa activity (ng/mL) Standard Deviation 30.6	77.5 Anti-FXa activity (ng/mL) Standard Deviation 30.8	87.5 Anti-FXa activity (ng/mL) Standard Deviation 45.5
Anti-FXa Activity Day 8	55.2 Anti-FXa activity (ng/mL) Standard Deviation 8.96	—	47.5 Anti-FXa activity (ng/mL) Standard Deviation 10.6	48 Anti-FXa activity (ng/mL) Standard Deviation 11.3
Anti-FXa Activity Day 15	70.2 Anti-FXa activity (ng/mL) Standard Deviation 28	75.3 Anti-FXa activity (ng/mL) Standard Deviation 33.9	63.9 Anti-FXa activity (ng/mL) Standard Deviation 21.6	64.8 Anti-FXa activity (ng/mL) Standard Deviation 25.3

Adverse Events

Apixaban

Serious events: 91 serious events

Other events: 204 other events

Deaths: 1 deaths

Standard of Care

Serious events: 83 serious events

Other events: 193 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER