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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01684423




Registration number
NCT01684423
Ethics application status
Date submitted
11/09/2012
Date registered
13/09/2012
Date last updated
21/09/2017

Titles & IDs
Public title
Oral Rivaroxaban in Children With Venous Thrombosis
Scientific 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
Secondary ID [1] 0 0
2011-004539-30
Secondary ID [2] 0 0
14373
Universal Trial Number (UTN)
Trial acronym
EINSTEINJunior
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Venous Thrombosis 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Blood 0 0 0 0
Clotting disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Rivaroxaban (Xarelto, BAY59-7939)
Treatment: Drugs - Active comparator
Treatment: Drugs - Rivaroxaban (BAY59-7939) suspension

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.

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).

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.

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.

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).


Treatment: Drugs: 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.

Treatment: Drugs: 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).

Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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).
Timepoint [1] 0 0
From start of study drug administration until end of the 30-day treatment period
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
From start of study drug administration until end of the 30-day treatment period
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Repeat imaging at the end of the 30 day treatment period
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31
Secondary outcome [5] 0 0
Anti-factor Xa Values at Specified Time Points - The individual anti-Factor Xa activity was determined ex-vivo using a photometric method.
Timepoint [5] 0 0
0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31
Secondary outcome [6] 0 0
Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Specified Time Points - Geometric and percentage geometric coefficient of variation (%CV) were reported.
Timepoint [6] 0 0
0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31

Eligibility
Key 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
Minimum age
6 Years
Maximum age
17 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
- Westmead
Recruitment hospital [2] 0 0
- Parkville
Recruitment hospital [3] 0 0
- South Brisbane
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
Austria
State/province [12] 0 0
Oberösterreich
Country [13] 0 0
Austria
State/province [13] 0 0
Steiermark
Country [14] 0 0
Austria
State/province [14] 0 0
Tirol
Country [15] 0 0
Austria
State/province [15] 0 0
Wien
Country [16] 0 0
Canada
State/province [16] 0 0
Alberta
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
Canada
State/province [18] 0 0
Quebec
Country [19] 0 0
France
State/province [19] 0 0
BORDEAUX cedex
Country [20] 0 0
France
State/province [20] 0 0
Montpellier Cedex
Country [21] 0 0
France
State/province [21] 0 0
NANTES Cedex 1
Country [22] 0 0
France
State/province [22] 0 0
Paris
Country [23] 0 0
France
State/province [23] 0 0
Rennes Cedex
Country [24] 0 0
France
State/province [24] 0 0
TOULOUSE Cedex 9
Country [25] 0 0
Germany
State/province [25] 0 0
Baden-Württemberg
Country [26] 0 0
Germany
State/province [26] 0 0
Bayern
Country [27] 0 0
Germany
State/province [27] 0 0
Hessen
Country [28] 0 0
Germany
State/province [28] 0 0
Sachsen
Country [29] 0 0
Germany
State/province [29] 0 0
Schleswig-Holstein
Country [30] 0 0
Germany
State/province [30] 0 0
Berlin
Country [31] 0 0
Israel
State/province [31] 0 0
Beer Sheva
Country [32] 0 0
Israel
State/province [32] 0 0
Haifa
Country [33] 0 0
Israel
State/province [33] 0 0
Jerusalem
Country [34] 0 0
Israel
State/province [34] 0 0
Petach Tikva
Country [35] 0 0
Israel
State/province [35] 0 0
Ramat Gan
Country [36] 0 0
Italy
State/province [36] 0 0
Liguria
Country [37] 0 0
Italy
State/province [37] 0 0
Lombardia
Country [38] 0 0
Italy
State/province [38] 0 0
Piemonte
Country [39] 0 0
Italy
State/province [39] 0 0
Puglia
Country [40] 0 0
Italy
State/province [40] 0 0
Veneto
Country [41] 0 0
Netherlands
State/province [41] 0 0
Amsterdam
Country [42] 0 0
Netherlands
State/province [42] 0 0
Nijmegen
Country [43] 0 0
Netherlands
State/province [43] 0 0
Rotterdam
Country [44] 0 0
Netherlands
State/province [44] 0 0
Utrecht
Country [45] 0 0
Switzerland
State/province [45] 0 0
Basel-Stadt
Country [46] 0 0
Switzerland
State/province [46] 0 0
Sankt Gallen
Country [47] 0 0
Switzerland
State/province [47] 0 0
Bern
Country [48] 0 0
Switzerland
State/province [48] 0 0
Luzern
Country [49] 0 0
Switzerland
State/province [49] 0 0
Zürich

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bayer
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Janssen Research & Development, LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01684423
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications