Back to resultsOral Rivaroxaban in Children With Venous Thrombosis (EINSTEINJunior)
Primary Purpose
Venous Thrombosis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Rivaroxaban (Xarelto, BAY59-7939)
Active comparator
Rivaroxaban (BAY59-7939) suspension
Sponsored by
About this trial
This is an interventional treatment trial for Venous Thrombosis
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Active Comparator
Experimental
Experimental
Active Comparator
Arm Label
Rivaroxaban (BAY59-7939) tablet, OD, Age: 12 - <18
Comparator, Age: 12 - <18 years
Rivaroxaban (BAY59-7939) tablet, OD, Age: 6 - <12 years
Rivaroxaban (BAY59-7939) suspension, BID, Age: 6 - <12 years
Comparator, Age: 6 - <12 years
Arm 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.
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).
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.
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.
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).
Outcomes
Primary Outcome Measures
Number of Subjects With Major and Clinically Relevant Non-Major Bleeding Events
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
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
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
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
The Activated partial thromboplastin time (aPTT) is a screening test for the intrinsic pathway.
Anti-factor Xa Values at Specified Time Points
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
Geometric and percentage geometric coefficient of variation (%CV) were reported.
Full Information
NCT ID
NCT01684423
First Posted
September 11, 2012
Last Updated
August 25, 2017
Sponsor
Bayer
Collaborators
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT01684423
Brief Title
Oral Rivaroxaban in Children With Venous Thrombosis
Acronym
EINSTEINJunior
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
February 19, 2013 (Actual)
Primary Completion Date
September 1, 2016 (Actual)
Study Completion Date
September 1, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer
Collaborators
Janssen Research & Development, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Venous Thrombosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
64 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rivaroxaban (BAY59-7939) tablet, OD, Age: 12 - <18
Arm Type
Experimental
Arm 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.
Arm Title
Comparator, Age: 12 - <18 years
Arm Type
Active Comparator
Arm 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).
Arm Title
Rivaroxaban (BAY59-7939) tablet, OD, Age: 6 - <12 years
Arm Type
Experimental
Arm 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.
Arm Title
Rivaroxaban (BAY59-7939) suspension, BID, Age: 6 - <12 years
Arm Type
Experimental
Arm 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.
Arm Title
Comparator, Age: 6 - <12 years
Arm Type
Active Comparator
Arm 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).
Intervention Type
Drug
Intervention Name(s)
Rivaroxaban (Xarelto, BAY59-7939)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Active comparator
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Rivaroxaban (BAY59-7939) suspension
Intervention Description
Subjects aged were administered with age- and body weight-adjusted oral dose of rivaroxaban (BAY59-7939) suspension under fed conditions twice daily.
Primary Outcome Measure Information:
Title
Number of Subjects With Major and Clinically Relevant Non-Major Bleeding Events
Description
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).
Time Frame
From start of study drug administration until end of the 30-day treatment period
Secondary Outcome Measure Information:
Title
Number of Subjects With Symptomatic Recurrent Venous Thromboembolism
Description
The occurrence of recurrent venous thromboembolism was summarized by age group. Symptomatic recurrence of venous thrombosis was documented by the appropriate imaging test.
Time Frame
From start of study drug administration until end of the 30-day treatment period
Title
Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden
Description
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.
Time Frame
Repeat imaging at the end of the 30 day treatment period
Title
Change From Baseline in Prothrombin Time at Specified Time Points
Description
Prothrombin time is a global clotting test used for the assessment of the extrinsic pathway of the blood coagulation cascade.
Time Frame
0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31
Title
Change From Baseline in Activated Partial Thromboplastin Time at Specified Time Points
Description
The Activated partial thromboplastin time (aPTT) is a screening test for the intrinsic pathway.
Time Frame
0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31
Title
Anti-factor Xa Values at Specified Time Points
Description
The individual anti-Factor Xa activity was determined ex-vivo using a photometric method.
Time Frame
0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31
Title
Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Specified Time Points
Description
Geometric and percentage geometric coefficient of variation (%CV) were reported.
Time Frame
0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202-3500
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027-6089
Country
United States
City
Orange
State/Province
California
ZIP/Postal Code
92868-3974
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201-2196
Country
United States
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
City
New Hyde Park
State/Province
New York
ZIP/Postal Code
11040
Country
United States
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106-2602
Country
United States
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205-2696
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
City
South Brisbane
ZIP/Postal Code
4101
Country
Australia
City
Linz
State/Province
Oberösterreich
ZIP/Postal Code
4020
Country
Austria
City
Graz
State/Province
Steiermark
ZIP/Postal Code
8036
Country
Austria
City
Innsbruck
State/Province
Tirol
ZIP/Postal Code
6020
Country
Austria
City
Wien
ZIP/Postal Code
1090
Country
Austria
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2B7
Country
Canada
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 3Z5
Country
Canada
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L1
Country
Canada
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
City
Quebec
ZIP/Postal Code
G1V 4G2
Country
Canada
City
BORDEAUX cedex
ZIP/Postal Code
33076
Country
France
City
Montpellier Cedex
ZIP/Postal Code
34295
Country
France
City
NANTES Cedex 1
ZIP/Postal Code
44093
Country
France
City
Paris
ZIP/Postal Code
75015
Country
France
City
Paris
ZIP/Postal Code
75019
Country
France
City
Rennes Cedex
ZIP/Postal Code
35033
Country
France
City
TOULOUSE Cedex 9
ZIP/Postal Code
31059
Country
France
City
Freiburg
State/Province
Baden-Württemberg
ZIP/Postal Code
79106
Country
Germany
City
Erlangen
State/Province
Bayern
ZIP/Postal Code
91054
Country
Germany
City
Frankfurt
State/Province
Hessen
ZIP/Postal Code
60590
Country
Germany
City
Dresden
State/Province
Sachsen
ZIP/Postal Code
01307
Country
Germany
City
Lübeck
State/Province
Schleswig-Holstein
ZIP/Postal Code
23538
Country
Germany
City
Berlin
ZIP/Postal Code
13353
Country
Germany
City
Beer Sheva
ZIP/Postal Code
8410101
Country
Israel
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
City
Jerusalem
ZIP/Postal Code
9112001
Country
Israel
City
Petach Tikva
ZIP/Postal Code
4920235
Country
Israel
City
Ramat Gan
ZIP/Postal Code
5262000
Country
Israel
City
Genova
State/Province
Liguria
ZIP/Postal Code
16147
Country
Italy
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20122
Country
Italy
City
Pavia
State/Province
Lombardia
ZIP/Postal Code
27100
Country
Italy
City
Torino
State/Province
Piemonte
ZIP/Postal Code
10126
Country
Italy
City
Bari
State/Province
Puglia
ZIP/Postal Code
70124
Country
Italy
City
Padova
State/Province
Veneto
ZIP/Postal Code
35128
Country
Italy
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
City
Amsterdam
Country
Netherlands
City
Nijmegen
ZIP/Postal Code
6525 GA
Country
Netherlands
City
Rotterdam
ZIP/Postal Code
3015 GJ
Country
Netherlands
City
Utrecht
ZIP/Postal Code
3584 CX
Country
Netherlands
City
Basel
State/Province
Basel-Stadt
ZIP/Postal Code
4056
Country
Switzerland
City
St. Gallen
State/Province
Sankt Gallen
ZIP/Postal Code
9006
Country
Switzerland
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
City
Luzern
ZIP/Postal Code
6000
Country
Switzerland
City
Zürich
ZIP/Postal Code
8032
Country
Switzerland
12. IPD Sharing Statement
Links:
URL
http://www.clinicaltrialsregister.eu/
Description
Click here to find information about studies related to Bayer Healthcare products conducted in Europe
Learn more about this trial
Oral Rivaroxaban in Children With Venous Thrombosis
We'll reach out to this number within 24 hrs