To investigate the safety and pharmacokinetics of apixaban in children with congenital or acquired heart disease who have a need for anticoagulation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
192
Specified dose on specified days
Specified dose on specified days
Specified dose on specified days
Composite of Adjudicated Major or Clinically Relevant Non-Major (CRNM) Bleeding Events
The number of participants with adjudicated major or CRNM bleeding events per the Perinatal and Paediatric Haemostasis Subcommittee of International Society on Thrombosis and Haemostasis (ISTH) criteria. Events are adjudicated by a blinded, independent events adjudication committee (EAC). Major bleeding satisfies one or more of the following criteria: fatal bleeding, clinically overt bleeding associated with a decrease in hemoglobin of at least 20 g/L (i.e., 2 g/dL) in a 24-hour period, bleeding that is retroperitoneal, pulmonary, intracranial, or otherwise involves the CNS, or bleeding that requires surgical intervention in an operating suite, including interventional radiology. CRNM bleeding satisfies one or both of the following criteria: overt bleeding for which blood product is administered and not directly attributable to the subject's underlying medical condition or bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating room.
Time frame: From first dose to 2 days after last dose (Up to approximately 12 months)
The Number of Participants With Thrombotic Events and Thromboembolic Event-Related Death
The number of participants with thromboembolic events (intra-cardiac, shunt, inside Fontan pathway, pulmonary embolism (PE), stroke, other arterial or venous thromboembolic events, etc.) and thromboembolic event-related death detected by imaging or clinical diagnosis. Death and thromboembolic events are adjudicated by a blinded, independent events adjudication committee (EAC)
Time frame: From randomization to 2 days after last dose (Up to approximately 12 months)
The Number of Participants With Adjudicated Major Bleeding
The number of participants with adjudicated major bleeding events per the Perinatal and Paediatric Haemostasis Subcommittee of International Society on Thrombosis and Haemostasis (ISTH) criteria. Major bleeding events are adjudicated by a blinded, independent events adjudication committee (EAC). Major bleeding is defined as bleeding that satisfies one or more of the following criteria: * fatal bleeding * clinically overt bleeding associated with a decrease in hemoglobin of at least 20 g/L (i.e., 2 g/dL) in a 24-hour period * bleeding that is retroperitoneal, pulmonary, intracranial, or otherwise involves the CNS * bleeding that requires surgical intervention in an operating suite, including interventional radiology
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Phoenix Children'S Hospital
Phoenix, Arizona, United States
University Of California San Diego
La Jolla, California, United States
Children'S Hospital Colorado
Aurora, Colorado, United States
Childrens Healthcare Of Atlanta
Atlanta, Georgia, United States
Local Institution - 0008
Indianapolis, Indiana, United States
Local Institution - 0009
Boston, Massachusetts, United States
Local Institution - 0013
Ann Arbor, Michigan, United States
Childrens Mercy Hospital
Kansas City, Missouri, United States
Local Institution - 0006
Cincinnati, Ohio, United States
Childrens Hospital Of Philadelphia
Philadelphia, Pennsylvania, United States
...and 36 more locations
Time frame: From first dose to 2 days after last dose (Up to approximately 12 months)
The Number of Participants With Adjudicated CRNM Bleeding
The number of participants with adjudicated clinically relevant non-major (CRNM) bleeding events per the Perinatal and Paediatric Haemostasis Subcommittee of International Society on Thrombosis and Haemostasis (ISTH) criteria. CRNM bleeding events are adjudicated by a blinded, independent events adjudication committee (EAC). CRNM bleeding is defined as bleeding that satisfies one or both of the following criteria: * overt bleeding for which blood product is administered and not directly attributable to the subject's underlying medical condition * bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating room
Time frame: From first dose to 2 days after last dose (Up to approximately 12 months)
The Number of Participants With All Adjudicated Bleeding
The number of participants with all adjudicated bleeding events
Time frame: From first dose to 2 days after last dose (Up to approximately 12 months)
The Number of Participants With Drug Discontinuation Due to Adverse Effects, Intolerability, or Bleeding
The number of participants with drug discontinuation due to adverse effects, intolerability, or bleeding.
Time frame: From first dose to 2 days after last dose (Up to approximately 12 months)
The Number of Participant Deaths in the Study
The number of participant deaths in the study.
Time frame: From first dose to 2 days after last dose (Up to approximately 12 months)
Maximum Observed Concentration (Cmax)
Time frame: From first dose up to 6 months after first dose
Trough Observed Concentration (Cmin)
Time frame: From first dose up to 6 months after first dose
Area Under the Concentration-Time Curve in One Dosing Interval (AUC (TAU))
Time frame: From first dose up to 6 months after first dose
Time of Maximum Observed Concentration (Tmax)
Time frame: From first dose up to 6 months after first dose
Anti-FXa Activity
Anti-FXa Activity was measured to assess participant plasma apixaban levels. 125 participants received at least one dose of apixaban and had anti-FXa samples collected that contributed measurements to at least one of the timepoints below.
Time frame: From first dose up to 6 months after first dose
Chromogenic FX Assay (Apparent FX Level)
Chromogenic FX was measured to assess (apparent) FX levels in participants and inhibition of FXa by apixaban. 125 participants received at least one dose of apixaban and had chromogenic FX assay samples collected that contributed measurements to at least one of the timepoints below.
Time frame: From first dose up to 6 months after first dose
The Child and Parent Reports of Pediatric Quality of Life Inventory (PedsQL)
Subjects' quality of life was measured using the PedsQL instrument administered only to English-speaking children/parents. Only subjects who completed the questionnaires at both baseline and post-baseline visits were included in the analyses. PedsQL consists of 23 items scored on a 5-point Likert scale from 0 (never) to 4 (almost always) or for the child report for younger children ages 5-7, a 3-point Likert scale: 0 (Not at all), 2 (Sometimes), and 4 (A lot). Scores are reverse scored and transformed to a 0-100 scale as follows: 0=100, 1=75, 3=25, 4=0. Higher scores indicate a better HRQOL and/or lower problems.
Time frame: from randomization up to 12 months after randomization
Kids Informed Decrease Complications Learning on Thrombosis (KIDCLOT) IMPACT Score
Subjects' quality of life was measured using the KIDCLOT instrument administered only to English-speaking children/parents. Only subjects who completed the questionnaires at both baseline and post-baseline visits were included in the analyses. KIDCLOT Parent inventory uses a 5 point Likert scale from 1 (N/A), 2 (Never), 3 (Rarely), 4 ( Now and then), 5 (Often). Child inventory uses a 4 point Likert scale 1 (N/A), 2 (Never), 3 (Now and then), 5 (Always). Values are scores as follows 1=0, 2=1, 3=2, 4=3, 5=4. Score interpretation is 0 to 100 percent IMPACT of anticoagulation on a child's life therefore, higher scores indicates a more negative effect.
Time frame: from randomization up to 12 months after randomization