EINSTEIN Junior: Oral Rivaroxaban in Children With Venous Thrombosis (EINSTEIN Jr)

Bayer

Status and phase: Completed; Phase 3

Conditions: Venous Thromboembolism

Treatments: Drug: Standard of Care; Drug: Rivaroxaban (Xarelto, BAY59-7939)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02234843

2014-000565-47 (EudraCT Number)

14372

Details and patient eligibility

About

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

Enrollment: 500 patients

Sex: All

Ages: Under 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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500 participants in 2 patient groups

BAY59-7939

Experimental group

Description:

Rivaroxaban (tablets and oral suspension) Dose: Age and body weight-adjusted dosing of rivaroxaban to achieve a similar exposure as that observed in adults treated for venous thromboembolism (VTE) with 20 mg rivaroxaban.

Treatment:

Drug: Rivaroxaban (Xarelto, BAY59-7939)

Drug: Rivaroxaban (Xarelto, BAY59-7939)

Standard of Care

Experimental group

Description:

Subcutaneous low molecular weight heparin (LMWH), subcutaneous fondaparinux and/or oral vitamin K antagonist (VKA) Dose : as per standard of care

Treatment:

Drug: Standard of Care