In most children with central venous catheter-related venous thromboembolism (CVC-VTE), treatment with rivaroxaban or other standard anticoagulants reduced clot burden, according to results from a sub-study of the EINSTEIN-Jr. trial published in Blood Advances. While extended anticoagulation was associated with residual VTE in young children and continued CVC use, the researchers concluded that anticoagulation for this population was safe and efficacious.
According to study author Christoph Male, MD, of the Medical University of Vienna in Austria, many clinicians are cautious about using anticoagulant therapy in children with CVC-VTE, primarily because of the lack of solid data to support this approach. This concern is magnified for infants and neonates, he added. “The results of our study will give clinicians more confidence in using anticoagulant treatment in children with CVC-VTE of all ages, particularly as this treatment has been demonstrated to be quite safe,” Dr. Male told ASH Clinical News. “These data provide clinicians with valid data on the benefit-risk balance of using anticoagulants in this group of children.”
The present analysis was a sub-study of 126 children with symptomatic or asymptomatic CVC-VTE who were enrolled in the randomized, phase III EINSTEIN-Jr. trial, representing approximately one-quarter of the entire study population. These patients were randomized to receive either the oral anticoagulant rivaroxaban (n=90) or standard anticoagulants (n=36), which included heparin or vitamin K antagonists.
Treatment lasted for 1 month (30 days±7 days) for children <2 years of age and 3 months (90 days±7 days) for children ≥2 years. The median follow-up period was 31 days for children <2 years of age and 91 days for children ≥2 years of age.
The rate of CVC-VTE was highest among children between the ages of birth and 1 year (67%), followed by those aged 2 to 5 years (38%), 6 to 11 years (24%), and 12 to 17 years (14%). A greater proportion of children had symptomatic versus asymptomatic CVC-VTE (60% vs. 40%, respectively), and more than half (56%) had acute CVC-VTE.
None of the children in the sub-study cohort experienced symptomatic recurrent deep VTE, the investigators reported.
In addition, there were no reports of major bleeding, although 3 children (2.4%) experienced clinically relevant non-major bleeding events. All of these were reported in the rivaroxaban group, which was associated with an absolute risk difference of 3.3%, compared with standard anticoagulation.
Among 103 patients with repeat imaging test results, 55% (n=57) had complete vein recanalization, whereas 37% (n=38) had incomplete recanalization. In addition, 6.8% (n=7) had no relevant change and 1.0% (n=1) had asymptomatic deterioration.
Nearly half of children (n=61; 48%) continued anticoagulant therapy beyond the study period. Extended anticoagulation was associated with a higher risk of residual VTE, but only in children <2 years (odds ratio [OR] = 20.9; p=0.003), the authors reported. Presence of a CVC at the end of the study period also was independently associated with continued anticoagulant therapy (OR=6.7; p=0.002).
Dr. Male and researchers noted that the EINSTEIN-Jr. sub-study included a high proportion of patients with asymptomatic CVC-VTE, whose physicians had decided to administer anticoagulants in therapeutic doses. “As preserving a functional CVC, especially in the youngest children, may be of critical importance … pediatricians may elect anticoagulant treatment over a ‘watchful-waiting’ approach,” they wrote in discussing these results. “The absence of recurrent VTE and major bleeding and the high rate of complete and partial resolution of the CVC-VTE on repeat imaging seem to lend credence to the practice of anticoagulant therapy not only for symptomatic CVC-VTE but also for asymptomatic CVC-VTE.”
Limitations of this sub-study were the small sample size and the limited timeframe of 1 to 3 months in which efficacy and safety outcomes were monitored.
Study authors report relationships with Bayer and Janssen Research & Development, which sponsored this trial.
Thom K, Lensing AWA, Nurmeev I, et al. Safety and efficacy of anticoagulant therapy in pediatric catheter-related venous thrombosis (EINSTEIN-Jr. CVC-VTE). Blood Adv. [Epub ahead of print]