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Randomized Controlled Trial
. 2020 Dec 22;4(24):6250-6258.
doi: 10.1182/bloodadvances.2020003244.

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

Philip Connor  1 , Mayte Sánchez van Kammen  2 , Anthonie W A Lensing  3 , Elizabeth Chalmers  4 , Krisztián Kállay  5 , Kerry Hege  6 , Paolo Simioni  7 , Tina Biss  8 , Fanny Bajolle  9 , Damien Bonnet  9 , Sebastian Grunt  10 , Riten Kumar  11 , Olga Lvova  12 , Rukhmi Bhat  13 , An Van Damme  14 , Joseph Palumbo  15 , Amparo Santamaria  16 , Paola Saracco  17 , Jeanette Payne  18 , Susan Baird  19 , Kamar Godder  20 , Veerle Labarque  21 , Christoph Male  22 , Ida Martinelli  23 , Michelle Morales Soto  24 , Jayashree Motwani  25 , Sanjay Shah  26 , Helene L Hooimeijer  27 , Martin H Prins  28 , Dagmar Kubitza  3 , William T Smith  28 , Scott D Berkowitz  29 , Akos F Pap  3 , Madhurima Majumder  29 , Paul Monagle  30   31   32 , Jonathan M Coutinho  2
Affiliations
Randomized Controlled Trial

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

Philip Connor et al. Blood Adv. .

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.

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Conflict of interest statement

Conflict-of-interest disclosure: P.C., K.K., P. Simioni, T.B., S.G., R.B., A.V.D., J. Palumbo, P. Saracco, J. Payne, S.B., K.G., V.L., I.M., M.M.S., J.M., S.S., H.L.H., P.M., and J.M.C. report fees paid to their institutions from Bayer. A.W.A.L., D.K., W.T.S., S.D.B., A.F.P. and M.M. are employees of Bayer. E.C. has received personal fees from Boehringer Ingelheim and Bristol-Myers Squibb and reports fees paid to her institution from Bayer. D.B. has received personal fees and grant support from Actelion Pharmaceuticals and Novartis and reports fees paid to his institution from Bayer. O.L. has received personal fees from Bayer and reports fees paid to her institution from Bayer, Pfizer, and Boehringer Ingelheim. C.M. has received personal fees and reports fees paid to his institution from Bayer, Bristol-Myers Squibb, and Pfizer and reports fees paid to his institution from Boehringer-Ingelheim. K.H., R.K., and A.S. have received personal fees and report fees paid to their institution from Bayer. M.H.P. has received personal fees from Bayer. M.S.v.K. and F.B. declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Flowchart of selection of patients for the EINSTEIN-Jr CVT substudy. *Withdrew from the study before any of the outcomes had occurred.
See this image and copyright information in PMC

References

    1. deVeber G, Andrew M, Adams C, et al. ; Canadian Pediatric Ischemic Stroke Study Group . Cerebral sinovenous thrombosis in children. N Engl J Med. 2001;345(6):417-423. - PubMed
    1. Silvis SM, de Sousa DA, Ferro JM, Coutinho JM. Cerebral venous thrombosis. Nat Rev Neurol. 2017;13(9):555-565. - PubMed
    1. Ichord RN, Benedict SL, Chan AK, Kirkham FJ, Nowak-Göttl U; International Paediatric Stroke Study Group . Paediatric cerebral sinovenous thrombosis: findings of the International Paediatric Stroke Study. Arch Dis Child. 2015;100(2):174-179. - PubMed
    1. Heller C, Heinecke A, Junker R, et al. ; Childhood Stroke Study Group . Cerebral venous thrombosis in children: a multifactorial origin. Circulation. 2003;108(11):1362-1367. - PubMed
    1. Sébire G, Tabarki B, Saunders DE, et al. . Cerebral venous sinus thrombosis in children: risk factors, presentation, diagnosis and outcome. Brain. 2005;128(pt 3):477-489. - PubMed

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