EINSTEIN Junior: Oral Rivaroxaban in Children With Venous Thrombosis
Condition: Venous Thromboembolism
MeSH terms: Thromboembolism; Venous Thromboembolism
Intervention: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban (Xarelto, BAY59-7939); Standard of Care
Intervention description: Age and body weight-adjusted dosing equivalent to 20 mg rivaroxaban in adults, once daily or twice daily, as tablets; Age and body weight-adjusted dosing equivalent to 20 mg rivaroxaban in adults, once daily, twice daily or three times daily, as oral suspension; LMWH (low molecular weight heparin) or fondaparinux or vitamin K antagonist (VKA) therapy.
dose : as per standard of care
Intervention MeSH terms: Rivaroxaban
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 500.0
Sex: All
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Pediatric

Summary:

      The purpose of this study is to evaluate comparative efficacy and safety of rivaroxaban to
      standard of care in children with acute venous thromboembolism.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Children aged birth to < 18 years with confirmed venous thromboembolism who receive
             initial treatment with therapeutic dosages of UFH (unfractionated heparin), LMWH (low
             molecular weight heparin) or fondaparinux and require anticoagulant therapy for at
             least 90 days. However, children aged birth to < 2 years with catheter-related
             thrombosis require anticoagulant therapy for at least 30 days.

          -  For children younger than 6 months:

               -  Gestational age at birth of at least 37 weeks.

               -  Oral feeding/nasogastric/gastric feeding for at least 10 days.

               -  Body weight ≥2600 g

        Exclusion Criteria:

          -  Active bleeding or bleeding risk contraindicating anticoagulant therapy

          -  An estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m*2 (in children
             younger than 1 year, serum creatinine results above 97.5th percentile excludes
             participation)

          -  Hepatic disease which is associated with either: coagulopathy leading to a clinically
             relevant bleeding risk, or ALT> 5x upper level of normal (ULN) or total bilirubin > 2x
             ULN with direct bilirubin > 20% of the total

          -  Platelet count < 50 x 109/L

          -  Sustained uncontrolled hypertension defined as > 95th age percentile

          -  Life expectancy < 3 months

          -  Concomitant use of strong inhibitors of both cytochrome P450 isoenzyme 3A4 (CYP3A4)
             and P-glycoprotein (P-gp), including but not limited to all human immunodeficiency
             virus protease inhibitors and the following azole antimycotics agents: ketoconazole,
             itraconazole, voriconazole, posaconazole, if used systemically

          -  Concomitant use of strong inducers of CYP3A4, including but not limited to rifampicin,
             rifabutin, phenobarbital, phenytoin and carbamazepine

          -  Childbearing potential without proper contraceptive measures, pregnancy or breast
             feeding