An international trial with Australian involvement suggests apixaban could offer children with venous thromboembolism an effective oral alternative to injections, without increasing major bleeding.
The largest trial of apixaban in paediatric venous thromboembolism has found the oral anticoagulant performed as well as standard therapy without increasing major bleeding, offering the potential for a simpler treatment option, researchers say.
Published in The Lancet Haematology, the multinational phase 3 study found fixed-dose, weight-based apixaban achieved similarly low rates of recurrent venous thromboembolism (VTE) compared with conventional anticoagulation while avoiding the need for routine injections or frequent laboratory monitoring.
“To our knowledge, the total number of neonates and younger paediatric patients (<2 years) included in this study is larger than in other prospective, randomised paediatric DOAC studies for the treatment of venous thromboembolism conducted to date,” the researchers wrote.
“The results show that use of a fixed-dose-by-bodyweight-tier regimen resulted in numerically similar and low recurrence risk for venous thromboembolism compared with the standard-of-care group, without an increase in major or clinically relevant non-major bleeding in paediatric patients, including the most vulnerable patients (<2 years).”
For paediatric haematologists, the findings add a third direct oral anticoagulant (DOAC) to the growing evidence base supporting a move away from low-molecular-weight heparin and warfarin in children.
While venous thromboembolism remains uncommon in childhood, its incidence has climbed steadily over the past two decades, driven by improved survival of critically ill children, greater use of central venous catheters, and better recognition of the condition.
Yet treatment options have lagged behind adults, with most children still requiring injections for weeks or months.
“Apixaban, an orally administered direct factor Xa (FXa) inhibitor, is currently approved globally for the treatment and prevention of recurrent deep vein thrombosis or pulmonary embolism in adults,” the researchers wrote.
“In adults, the efficacy of apixaban is similar to that of heparinoids and VKAs, and its safety profile is characterised by a significantly lower risk of major bleeding and clinically relevant non-major bleeding.
“Therefore, apixaban, along with other DOACs, is increasingly being used in place of traditional anticoagulant treatments in some regions.
“This clinical trial was conducted to assess the efficacy, safety, and pharmacokinetics of apixaban for the treatment of venous thromboembolism and prevention of recurrent venous thromboembolism in patients younger than 18 years.”
The international trial recruited 229 patients younger than 18 years across 120 sites in 14 countries between 2015 and 2024. Investigators included clinicians from the Kids Cancer Centre at Prince of Wales Hospital in Sydney, alongside centres predominantly in the US, Canada, the UK, and Europe.
Participants were randomised in a 2:1 ratio to receive oral apixaban or standard anticoagulation with unfractionated heparin, low-molecular-weight heparin, or vitamin K antagonists according to local practice.
Children were treated for 12 weeks, with younger patients eligible for shorter courses where clinically appropriate. Dosing was based on body weight, with neonates receiving pharmacokinetic-guided adjustments during the early phase of treatment.
The primary efficacy endpoint – a composite of recurrent VTE and VTE-related death – occurred in four of 155 children (2.6%) treated with apixaban and two of 74 children (2.7%) receiving standard care. All events represented recurrent thrombosis; there were no VTE-related deaths in either group.
Safety outcomes were similarly reassuring. No major bleeding events occurred in either treatment arm. Clinically relevant non-major bleeding affected two children (1.3%) receiving apixaban and one child (1.4%) receiving standard therapy.
Overall adverse event rates were nearly identical between groups, with headache, epistaxis, and vomiting among the most commonly reported events.
The researchers said the findings demonstrated that a fixed-dose, weight-tiered apixaban regimen produced efficacy and safety comparable to conventional anticoagulation, while offering the practical advantages of oral administration.
“Establishing a consistent pharmacokinetics and pharmacodynamics profile for an oral anticoagulant in paediatric patients according to a weight-based dosing algorithm across all age groups is of particular importance to extend the benefits of oral administration to children without the need for parenteral anticoagulant administration or therapeutic drug monitoring,” they wrote.
“The pharmacokinetics and pharmacodynamics profile of apixaban showed excellent absorption in children with an intact gastrointestinal tract.”
The study also included more infants and neonates than previous prospective paediatric DOAC trials, strengthening evidence in one of the most difficult populations to study.
Sixteen neonates were enrolled overall, with dedicated pharmacokinetic analyses confirming that weight-based dosing achieved drug exposures similar to those seen in adults.
Most participants were adolescents, reflecting the epidemiology of paediatric thrombosis, with the median age just over 14 years.
Deep vein thrombosis accounted for more than half of index events, followed by pulmonary embolism and other thrombotic presentations including cerebral venous sinus thrombosis and portal vein thrombosis.
Underlying medical complexity was common. Frequent risk factors included infection, congenital heart disease, obesity, malignancy, and the use of sex hormone therapy, highlighting the diverse clinical scenarios in which paediatric thrombosis now occurs.
The investigators acknowledged the study was descriptive rather than powered to demonstrate formal non-inferiority, meaning statistical comparisons between treatment groups were not planned.
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However, they said the consistency of efficacy and safety outcomes with adult apixaban studies, together with previous paediatric trials of rivaroxaban and dabigatran, strengthened confidence that DOACs have an expanding role in children.
An optional extension phase also provided encouraging longer-term data. Fifty-three children continued apixaban beyond the initial treatment period, with no recurrent thrombotic events, major bleeding, or VTE-related deaths observed during extended follow-up.
One finding likely to attract attention was a higher frequency of heavy menstrual bleeding among adolescent girls receiving apixaban, mirroring observations from adult studies.
Although none of these events resulted in treatment discontinuation and the study was not designed to assess menstrual bleeding specifically, the researchers said clinicians should remain aware of the issue when prescribing DOACs to adolescent females.
“In conclusion, the results from this study suggest that, when administered at weight-tiered doses intended to result in exposures numerically similar to those approved for adults, apixaban has a favourable risk–benefit profile for treatment and prevention of recurrence of venous thromboembolism in children, from birth to age 18 years,” the researchers wrote.
“No new or unexpected safety issues were identified in this study. The results also indicate that, when used at doses that correspond to adult exposures, the risk–benefit profile of apixaban in paediatric patients with an intact gastrointestinal tract is similar to that in adults, not requiring routine laboratory monitoring.”
The study was funded by Pfizer and Bristol Myers Squibb, which jointly market apixaban. Both companies were involved in study design, data collection, analysis, and manuscript preparation.
