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Oral Rivaroxaban in Children With Venous Thrombosis (EINSTEINJunior)

This study has been completed.
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01684423
First received: September 11, 2012
Last updated: August 25, 2017
Last verified: August 2017
  Purpose
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 Intervention Phase
Venous Thrombosis Drug: Rivaroxaban (Xarelto, BAY59-7939) Drug: Active comparator Drug: Rivaroxaban (BAY59-7939) suspension Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Bayer:

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.


Enrollment: 64
Actual Study Start Date: February 19, 2013
Study Completion Date: September 1, 2016
Primary Completion Date: September 1, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
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).
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).
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.
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.
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).
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).

  Eligibility

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01684423

  Show 59 Study Locations
Sponsors and Collaborators
Bayer
Janssen Research & Development, LLC
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01684423     History of Changes
Other Study ID Numbers: 14373
2011-004539-30 ( EudraCT Number )
Study First Received: September 11, 2012
Results First Received: August 25, 2017
Last Updated: August 25, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Venous Thrombosis
Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Vitamins
Vitamin K
Fondaparinux
Heparin
Rivaroxaban
Heparin, Low-Molecular-Weight
Dalteparin
Micronutrients
Growth Substances
Physiological Effects of Drugs
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Antifibrinolytic Agents
Hemostatics
Coagulants

ClinicalTrials.gov processed this record on September 21, 2017