Oral Rivaroxaban in Children With Venous Thrombosis (EINSTEINJunior)

August 25, 2017 updated by: Bayer

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
64

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • South Brisbane, Australia, 4101
    • New South Wales
      • Westmead, New South Wales, Australia, 2145
    • Victoria
      • Parkville, Victoria, Australia, 3052
  • Austria
      • Wien, Austria, 1090
    • Oberösterreich
      • Linz, Oberösterreich, Austria, 4020
    • Steiermark
      • Graz, Steiermark, Austria, 8036
    • Tirol
      • Innsbruck, Tirol, Austria, 6020
  • Canada
      • Quebec, Canada, G1V 4G2
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2B7
    • Ontario
      • Hamilton, Ontario, Canada, L8N 3Z5
      • Ottawa, Ontario, Canada, K1H 8L1
      • Toronto, Ontario, Canada, M5G 1X8
  • France
      • BORDEAUX cedex, France, 33076
      • Montpellier Cedex, France, 34295
      • NANTES Cedex 1, France, 44093
      • Paris, France, 75015
      • Paris, France, 75019
      • Rennes Cedex, France, 35033
      • TOULOUSE Cedex 9, France, 31059
  • Germany
      • Berlin, Germany, 13353
    • Baden-Württemberg
      • Freiburg, Baden-Württemberg, Germany, 79106
    • Bayern
      • Erlangen, Bayern, Germany, 91054
    • Hessen
      • Frankfurt, Hessen, Germany, 60590
    • Sachsen
      • Dresden, Sachsen, Germany, 01307
    • Schleswig-Holstein
      • Lübeck, Schleswig-Holstein, Germany, 23538
  • Israel
      • Beer Sheva, Israel, 8410101
      • Haifa, Israel, 3109601
      • Jerusalem, Israel, 9112001
      • Petach Tikva, Israel, 4920235
      • Ramat Gan, Israel, 5262000
  • Italy
    • Liguria
      • Genova, Liguria, Italy, 16147
    • Lombardia
      • Milano, Lombardia, Italy, 20122
      • Pavia, Lombardia, Italy, 27100
    • Piemonte
      • Torino, Piemonte, Italy, 10126
    • Puglia
      • Bari, Puglia, Italy, 70124
    • Veneto
      • Padova, Veneto, Italy, 35128
  • Netherlands
      • Amsterdam, Netherlands
      • Amsterdam, Netherlands, 1081 HV
      • Nijmegen, Netherlands, 6525 GA
      • Rotterdam, Netherlands, 3015 GJ
      • Utrecht, Netherlands, 3584 CX
  • Switzerland
      • Bern, Switzerland, 3010
      • Luzern, Switzerland, 6000
      • Zürich, Switzerland, 8032
    • Basel-Stadt
      • Basel, Basel-Stadt, Switzerland, 4056
    • Sankt Gallen
      • St. Gallen, Sankt Gallen, Switzerland, 9006
  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72202-3500
    • California
      • Los Angeles, California, United States, 90027-6089
      • Orange, California, United States, 92868-3974
    • Illinois
      • Chicago, Illinois, United States, 60611
    • Indiana
      • Indianapolis, Indiana, United States, 46202
    • Michigan
      • Detroit, Michigan, United States, 48201-2196
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
    • New York
      • New Hyde Park, New York, United States, 11040
    • Ohio
      • Cleveland, Ohio, United States, 44106-2602
      • Columbus, Ohio, United States, 43205-2696
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
    • Texas
      • Houston, Texas, United States, 77030
    • Virginia
      • Richmond, Virginia, United States, 23298

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

6 years to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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).
From start of study drug administration until end of the 30-day treatment period

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
From start of study drug administration until end of the 30-day treatment period
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.
Repeat imaging at the end of the 30 day treatment period
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.
0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31
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.
0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31
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.
0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31
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.
0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Bayer

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Janssen Research & Development, LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 19, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 11, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 11, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 13, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 21, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 25, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 14373
  • 2011-004539-30 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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