Oral Rivaroxaban in Children With Venous Thrombosis (EINSTEINJunior)
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| ClinicalTrials.gov Identifier: NCT01684423 |
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Recruitment Status :
Completed
First Posted : September 13, 2012
Results First Posted : September 21, 2017
Last Update Posted : September 21, 2017
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Sponsor:
Bayer
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Bayer
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Brief Summary:
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Venous Thrombosis | Drug: Rivaroxaban (Xarelto, BAY59-7939) Drug: Active comparator Drug: Rivaroxaban (BAY59-7939) suspension | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 64 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | 30-day, Single-arm Study of the Safety, Efficacy and the Pharmacokinetic and Pharmacodynamic Properties of Oral Rivaroxaban in Children With Various Manifestations of Venous Thrombosis |
| Actual Study Start Date : | February 19, 2013 |
| Actual Primary Completion Date : | September 1, 2016 |
| Actual Study Completion Date : | September 1, 2016 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Rivaroxaban
| Arm | Intervention/treatment |
|---|---|
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Experimental: Rivaroxaban (BAY59-7939) tablet, OD, Age: 12 - <18
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.
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Drug: Rivaroxaban (Xarelto, BAY59-7939)
Subjects were administered with age- and body weight-adjusted oral dose of rivaroxaban (BAY59-7939) IR tablet once daily under fed conditions for 30 days. |
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Active Comparator: Comparator, Age: 12 - <18 years
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).
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Drug: Active comparator
Subjects 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). |
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Experimental: Rivaroxaban (BAY59-7939) tablet, OD, Age: 6 - <12 years
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.
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Drug: Rivaroxaban (Xarelto, BAY59-7939)
Subjects were administered with age- and body weight-adjusted oral dose of rivaroxaban (BAY59-7939) IR tablet once daily under fed conditions for 30 days. |
|
Experimental: Rivaroxaban (BAY59-7939) suspension, BID, Age: 6 - <12 years
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.
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Drug: Rivaroxaban (BAY59-7939) suspension
Subjects aged were administered with age- and body weight-adjusted oral dose of rivaroxaban (BAY59-7939) suspension under fed conditions twice daily. |
|
Active Comparator: Comparator, Age: 6 - <12 years
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).
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Drug: Active comparator
Subjects 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). |
Primary Outcome Measures :
- Number of Subjects With Major and Clinically Relevant Non-Major Bleeding Events [ Time Frame: From start of study drug administration until end of the 30-day treatment period ]
Central independent adjudication committee (CIAC) classified bleeding as follows: Major bleeding is defined as overt bleeding and:
- associated with a fall in hemoglobin of 2 gram/decilitre (g/dL) or more, or
- leading to a transfusion of the equivalent of 2 or more units of packed red blood cells or whole blood in adults, or
- occurring in a critical site, e.g. intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal, or
- contributing to death.
Clinically relevant non-major bleeding is defined as overt bleeding not meeting the criteria for major bleeding, but associated with:
- medical intervention, or
- unscheduled contact (visit or telephone call) with a physician, or
- cessation (temporary) of study treatment, or
- discomfort for the child such as pain or
- impairment of activities of daily life (such as loss of school days or hospitalization).
Secondary Outcome Measures :
- Number of Subjects With Symptomatic Recurrent Venous Thromboembolism [ Time Frame: From start of study drug administration until end of the 30-day treatment period ]The occurrence of recurrent venous thromboembolism was summarized by age group. Symptomatic recurrence of venous thrombosis was documented by the appropriate imaging test.
- Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden [ Time Frame: Repeat imaging at the end of the 30 day treatment period ]The occurrence of asymptomatic deterioration in thrombotic burden was summarized by age group. Asymptomatic deterioration in thrombotic burden was documented by the appropriate imaging test and the results were classified as normalized, improved, no relevant change, deteriorated, not evaluable or not available.
- Change From Baseline in Prothrombin Time at Specified Time Points [ Time Frame: 0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31 ]Prothrombin time is a global clotting test used for the assessment of the extrinsic pathway of the blood coagulation cascade.
- Change From Baseline in Activated Partial Thromboplastin Time at Specified Time Points [ Time Frame: 0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31 ]The Activated partial thromboplastin time (aPTT) is a screening test for the intrinsic pathway.
- Anti-factor Xa Values at Specified Time Points [ Time Frame: 0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31 ]The individual anti-Factor Xa activity was determined ex-vivo using a photometric method.
- Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Specified Time Points [ Time Frame: 0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31 ]Geometric and percentage geometric coefficient of variation (%CV) were reported.
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| Ages Eligible for Study: | 6 Years to 17 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01684423
Locations
Show 59 study locations
Sponsors and Collaborators
Bayer
Janssen Research & Development, LLC
Investigators
| Study Director: | Bayer Study Director | Bayer |
Additional Information:
| Responsible Party: | Bayer |
| ClinicalTrials.gov Identifier: | NCT01684423 |
| Other Study ID Numbers: |
14373 2011-004539-30 ( EudraCT Number ) |
| First Posted: | September 13, 2012 Key Record Dates |
| Results First Posted: | September 21, 2017 |
| Last Update Posted: | September 21, 2017 |
| Last Verified: | August 2017 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Thrombosis Venous Thrombosis Embolism and Thrombosis Vascular Diseases Cardiovascular Diseases Rivaroxaban Factor Xa Inhibitors |
Antithrombins Serine Proteinase Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anticoagulants |