Oral Rivaroxaban in Children With Venous Thrombosis (EINSTEINJunior)

Bayer

Status and phase: Completed; Phase 2

Conditions: Venous Thrombosis

Treatments: Drug: Rivaroxaban (BAY59-7939) suspension; Drug: Rivaroxaban (Xarelto, BAY59-7939); Drug: Active comparator

Study type: Interventional

Funder types: Industry

Identifiers

NCT01684423

2011-004539-30 (EudraCT Number)

14373

Details and patient eligibility

About

The purpose of this study is to find out whether rivaroxaban is safe to use in children and how long it stays in the body. There will also be a check for bleeding and worsening of blood clots.

Enrollment: 64 patients

Sex: All

Ages: 6 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Children aged 6 to < 18 years with documented symptomatic or asymptomatic venous thrombosis treated for at least 2 months or, in case of catheter related thrombosis, treated for at least 6 weeks with LMWH (low molecular weight heparin), , fondaparinux and/or VKA (vitamin K antagonist).
• Informed consent provided and, if applicable, child assent provided

Exclusion criteria

• Active bleeding or high risk for bleeding contraindicating anticoagulant therapy
• Symptomatic progression of venous thrombosis during preceding anticoagulant treatment
• Planned invasive procedures, including lumbar puncture and removal of non peripherally placed central lines during study treatment
• An estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2
• Hepatic disease which is associated with 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 10^9/L
• 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), i.e. 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, i.e. rifampicin, rifabutin, phenobarbital, phenytoin and carbamazepine

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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64 participants in 5 patient groups

Rivaroxaban (BAY59-7939) tablet, OD, Age: 12 - <18

Experimental group

Description:

Subjects aged from 12 - \<18 years were administered with age and body weight-adjusted oral dose of rivaroxaban (BAY59-7939) IR (immediate-release) tablet once daily (OD) under fed conditions for 30 days. Subjects with a body weight of 14 to less than 50 kilogram (kg) received a dose (equivalent to 20 milligram \[mg\] in adults) ranging from 5 to 15 mg, and subjects with a body weight (comparable to adults) of greater than or equal to 50 kg received a dose of 20 mg.

Treatment:

Drug: Rivaroxaban (Xarelto, BAY59-7939)

Comparator, Age: 12 - <18 years

Active Comparator group

Description:

Subjects aged from 12 - \<18 years received comparator as per standard of care. The dosage given was to be adjusted based on the individual body weight (low molecular weight heparin, fondaparinux) or international normalized ratio (INR) adjusted (vitamin K antagonist).

Treatment:

Drug: Active comparator

Rivaroxaban (BAY59-7939) tablet, OD, Age: 6 - <12 years

Experimental group

Description:

Subjects aged from 6 - \<12 years were administered with age- and body weight-adjusted oral dose of rivaroxaban (BAY59-7939) IR tablet once daily under fed conditions for 30 days. Subjects with a body weight of 14 to less than 50 kg received a dose (equivalent to 20 mg in adults) ranging from 5 to 15 mg, and subjects with a body weight (comparable to adults) of greater than or equal to 50 kg received a dose of 20 mg.

Treatment:

Drug: Rivaroxaban (Xarelto, BAY59-7939)

Rivaroxaban (BAY59-7939) suspension, BID, Age: 6 - <12 years

Experimental group

Description:

Subjects aged from 6 - \<12 years were administered with age- and body weight-adjusted oral dose of rivaroxaban (BAY59-7939) suspension under fed conditions twice daily (BID). Subjects with a body weight of 9 to less than 50 kg received a total daily dose (equivalent to 20 mg in adults) ranging from 6.4 to 15 mg and subjects with a body weight of greater than or equal to 50 kg received a total daily dose of 20 mg.

Treatment:

Drug: Rivaroxaban (BAY59-7939) suspension

Comparator, Age: 6 - <12 years

Active Comparator group

Description:

Subjects aged from 6 - \<12 years received comparator as per standard of care. The dosage given was to be adjusted based on the individual body weight (low molecular weight heparin, fondaparinux) or INR-adjusted (vitamin K antagonist).

Treatment:

Drug: Active comparator