Safety and efficacy of rivaroxaban in pediatric cerebral venous thrombosis (EINSTEIN-Jr CVT).

Abstract

Anticoagulant treatment of pediatric cerebral venous thrombosis has not been evaluated in randomized trials. We evaluated the safety and efficacy of rivaroxaban and standard anticoagulants in the predefined subgroup of children with cerebral venous thrombosis (CVT) who participated in the EINSTEIN-Jr trial. Children with CVT were randomized (2:1), after initial heparinization, to treatment with rivaroxaban or standard anticoagulants (continued on heparin or switched to vitamin K antagonist). The main treatment period was 3 months. The primary efficacy outcome, symptomatic recurrent venous thromboembolism (VTE), and principal safety outcome, major or clinically relevant nonmajor bleeding,were centrally evaluated by blinded investigators. Sinus recanalization on repeat brain imaging was a secondary outcome. Statistical analyses were exploratory. In total, 114 children with confirmed CVT were randomized. All children completed the follow-up. None of the 73 rivaroxaban recipients and 1 (2.4%; CVT) of the 41 standard anticoagulant recipients had symptomatic, recurrent VTE after 3 months (absolute difference, 2.4%; 95% confidence interval [CI], -2.6% to 13.5%). Clinically relevant bleeding occurred in 5 (6.8%; all nonmajor and noncerebral) rivaroxaban recipients and in 1 (2.5%; major [subdural] bleeding) standard anticoagulant recipient (absolute difference, 4.4%; 95% CI, -6.7% to 13.4%). Complete or partial sinus recanalization occurred in 18 (25%) and 39 (53%) rivaroxaban recipients and in 6 (15%) and 24 (59%) standard anticoagulant recipients, respectively. In summary, in this substudy of a randomized trial with a limited sample size, children with CVT treated with rivaroxaban or standard anticoagulation had a low risk of recurrent VTE and clinically relevant bleeding. This trial was registered at clinicaltrials.gov as #NCT02234843.

• Authors: Philip Connor, Mayte Sánchez van Kammen, Anthonie W A Lensing, Elizabeth Chalmers, Krisztián Kállay, Kerry Hege, Paolo Simioni, Tina Biss, Fanny Bajolle, Damien Bonnet, Sebastian Grunt, Riten Kumar, Olga Lvova, Rukhmi Bhat, An Van Damme, Joseph Palumbo, Amparo Santamaria, Paola Saracco, Jeanette Payne, Susan Baird, Kamar Godder, Veerle Labarque, Christoph Male, Ida Martinelli, Michelle Morales Soto, Jayashree Motwani, Sanjay Shah, Helene L Hooimeijer, Martin H Prins, Dagmar Kubitza, William T Smith, Scott D Berkowitz, Akos F Pap, Madhurima Majumder, Paul Monagle, Jonathan M Coutinho
• Journal: Blood advances (Blood Adv) Vol. 4 Issue 24 Pg. 6250-6258 (12 22 2020) ISSN: 2473-9537 [Electronic] United States
• PMID: 33351120 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 by The American Society of Hematology.

Chemical References

• Anticoagulants
• Rivaroxaban

Topics

• Anticoagulants (adverse effects)
• Child
• Hemorrhage
• Humans
• Rivaroxaban (adverse effects)
• Venous Thromboembolism
• Venous Thrombosis (drug therapy)