Table 1.

Inclusion and exclusion criteria

Inclusion

1. Children aged 0 months to < 18 years with confirmed venous thromboembolism who receive initial treatment with therapeutic dosages of unfractionated heparin, low molecular weight heparin or fondaparinux and require anticoagulant therapy for at least 90 days. However, children aged 0 months to < 2 years with catheter-related thrombosis require anticoagulant therapy for at least 30 days.  2. Informed consent provided and, if applicable, child assent provided.  3. Children younger than 6 months need to have a gestational age at birth of at least 37 weeks, oral feeding/nasogastric/gastric feeding for at least 10 days, and body weight ≥ 2600 g.

Exclusion

1. Active bleeding or high risk of bleeding contraindicating anticoagulant therapy.  2. An estimated glomerular filtration rate < 30 mL/min/1.73 m2 (in children < 1 year: serum creatinine 97.5th percentile).  3. Hepatic disease which is associated with either: coagulopathy leading to a clinically relevant bleeding risk, or alanine aminotransferase > 5× ULN or total bilirubin > 2× ULN with direct bilirubin > 20% of the total.  4. Platelet count < 50 × 109/L.  5. Hypertension defined as systolic and/or diastolic blood pressure > 95th age percentile.  6. Life expectancy < 3 months.  7. Concomitant use of strong inhibitors of both cytochrome P450 isoenzyme 3A4 and P-glycoprotein, i.e. all human immunodeficiency virus protease inhibitors and the following azole-antimycotics agents: ketoconazole, itraconazole, voriconazole, posaconazole, if used systemically (fluconazole is allowed).  8. Concomitant use of strong inducers of cytochrome P450 isoenzyme 3A4, i.e. rifampicin, rifabutin, phenobarbital, phenytoin and carbamazepine.  9. Childbearing potential without proper contraceptive measures, pregnancy or breast feeding.  10. Hypersensitivity or any other contraindication listed in the local labeling for the comparator treatment or experimental treatment.  11. Inability to cooperate with the study procedures.  12. Previous assignment to treatment during this study.  13. Participation in a study with an investigational drug or medical device within 30 days prior to randomization.

ULN, upper level of normal