Apixaban for the Acute Treatment of Venous Thromboembolism in Children

Bleeding definitions are based on the Perinatal and Paediatric Haemostasis Subcommittee of the International Society on Thrombosis and Haemostasis (ISTH) criteria. Major bleeding includes: (i) fatal bleeding; (ii) clinically overt bleeding with a decrease in Hgb of at least 20 g/L (2 g/dL) in 24 hours; (iii) retroperitoneal, pulmonary, intracranial, or central nervous system bleeding; and (iv) bleeding requiring surgical intervention in an operating suite (including interventional radiology). Clinically relevant non-major bleeding includes: (i) overt bleeding requiring a blood product not attributable to the participant's underlying condition; and (ii) bleeding requiring medical or surgical intervention to restore hemostasis, other than in an operating suite.

Recurrent VTE, defined as either contiguous progression or non-contiguous new thrombus and including, but not limited to deep vein thrombosis (DVT), pulmonary embolism (PE) and paradoxical embolism. 95% CI was from the Agresti-Coull method.

Death due to any cause was assessed. 95% CI was calculated using the Agresti-Coull method.

Participants were assessed for death due to Venous Thromboembolism (VTE).

Index VTE status was defined as the last image obtained during the Main treatment phase for each participant's comparison to baseline imaging. Index VTE status was classified as Recurrence-contiguous; Recurrence-new; Unchanged; Regression; Resolution; Indeterminate/Nondiagnostic. Participants could have multiple concomitant index events. Regression was defined as (ie, unequivocal decrease [>50%] of the total volume/mass of the thrombus compared to the index event)

Participants were assessed for incidence of stroke.

Recurrent VTE, defined as either contiguous progression or non-contiguous new thrombus and including, but not limited to deep vein thrombosis (DVT), pulmonary embolism (PE) and paradoxical embolism. 95% CI was from the Agresti-Coull method.

Participants were assessed for incidence of Symptomatic or Asymptomatic Deep Vein Thrombosis (DVT) and New Symptomatic or Asymptomatic Pulmonary Embolism (PE).

Other VTE included events such as cerebral sinovenous thrombosis, renal vein thrombosis, portal vein thrombosis, catheter-related VTE, and splanchnic thrombosis. If VTE event type was blank, it was included in the Other VTE. 95% CI was from the Agresti-Coull method.

Bleeding definitions are based on the Perinatal and Paediatric Haemostasis Subcommittee of the International Society on Thrombosis and Haemostasis (ISTH) criteria. Major bleeding includes: (i) fatal bleeding; (ii) clinically overt bleeding with a decrease in Hgb of at least 20 g/L (2 g/dL) in 24 hours; (iii) retroperitoneal, pulmonary, intracranial, or central nervous system bleeding; and (iv) bleeding requiring surgical intervention in an operating suite (including interventional radiology). Clinically relevant non-major bleeding includes: (i) overt bleeding requiring a blood product not attributable to the participant's underlying condition; and (ii) bleeding requiring medical or surgical intervention to restore hemostasis, other than in an operating suite. Minor bleeding was defined as any overt or macroscopic evidence of bleeding that does not fulfill the above criteria for either major bleeding or clinically relevant, non-major bleeding.

Blood samples were collected to assess the apixaban concentration at specified timepoints. Day 1 PK concentrations were only collected for participants in the Birth to ≤27 days arm. The lower limit of quantification (LLOQ) is 1.0 ng/mL for plasma samples, and 0.5 ng/mL for dried blood samples.

Blood samples were collected to assess the Anti-Factor Xa concentration at specified timepoints. Day 1 PK concentrations were only collected for participants in the Birth to ≤27 days arm. The lower limit of quantification (LLOQ) is 35.0 ng/mL.