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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02234843




Registration number
NCT02234843
Ethics application status
Date submitted
5/09/2014
Date registered
9/09/2014
Date last updated
1/04/2020

Titles & IDs
Public title
EINSTEIN Junior: Oral Rivaroxaban in Children With Venous Thrombosis
Scientific title
Multicenter, Open-label, Active-controlled, Randomized Study to Evaluate the Efficacy and Safety of an age-and Body Weight-adjusted Rivaroxaban Regimen Compared to Standard of Care in Children With Acute Venous Thromboembolism
Secondary ID [1] 0 0
2014-000565-47
Secondary ID [2] 0 0
14372
Universal Trial Number (UTN)
Trial acronym
EINSTEIN Jr
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Venous Thromboembolism 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
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 - Rivaroxaban (Xarelto, BAY59-7939)
Treatment: Drugs - Standard of Care

Experimental: BAY59-7939 - Rivaroxaban (tablets and oral suspension) Dose: Age and body weight-adjusted dosing of rivaroxaban to achieve a similar exposure as that observed in adults treated for venous thromboembolism (VTE) with 20 mg rivaroxaban.

Experimental: Standard of Care - Subcutaneous low molecular weight heparin (LMWH), subcutaneous fondaparinux and/or oral vitamin K antagonist (VKA) Dose : as per standard of care


Treatment: Drugs: Rivaroxaban (Xarelto, BAY59-7939)
Age and body weight-adjusted dosing equivalent to 20 mg rivaroxaban in adults, once daily or twice daily, as tablets

Treatment: Drugs: Rivaroxaban (Xarelto, BAY59-7939)
Age and body weight-adjusted dosing equivalent to 20 mg rivaroxaban in adults, once daily, twice daily or three times daily, as oral suspension

Treatment: Drugs: Standard of Care
LMWH (low molecular weight heparin) or fondaparinux or vitamin K antagonist (VKA) therapy.

dose : as per standard of care

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

Outcomes
Primary outcome [1] 0 0
Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period
Timepoint [1] 0 0
During the main study treatment period (i.e., 3 months, except for children with central venous catheter venous thromboembolism (CVC-VTE) aged <2 years for whom it was 1 month)
Primary outcome [2] 0 0
Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period
Timepoint [2] 0 0
During the main study treatment period (i.e., 3 months, except for children with CVC-VTE aged <2 years for whom it was 1 month)
Primary outcome [3] 0 0
Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period
Timepoint [3] 0 0
During extended treatment period: up to month 12.
Primary outcome [4] 0 0
Number of Subjects With the Composite of All Symptomatic Recurrent Venous Thromboembolism During the 30 Days Post-study Treatment Period (i.e. >2 and = 30 Days After Stop of Study Medication)
Timepoint [4] 0 0
More than 2 and up to 30 days after stop of study medication
Primary outcome [5] 0 0
Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Main Treatment Period
Timepoint [5] 0 0
During the main study treatment period (i.e., 3 months, except for children with CVC-VTE aged <2 years for whom it was 1 month)
Primary outcome [6] 0 0
Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period
Timepoint [6] 0 0
During extended treatment period: up to month 12.
Secondary outcome [1] 0 0
Incidence Rates of the Composite of All Symptomatic Recurrent Venous Thromboembolism and Asymptomatic Deterioration in Thrombotic Burden on Repeat Imaging During the Main Treatment Period
Timepoint [1] 0 0
During the main study treatment period (i.e., 3 months, except for children with CVC-VTE aged <2 years for whom it was 1 month)
Secondary outcome [2] 0 0
AUC(0-24)ss in Plasma
Timepoint [2] 0 0
over 24 hours
Secondary outcome [3] 0 0
Cmax,ss in Plasma
Timepoint [3] 0 0
0 hours to 24 hours, 0 hours to 12 hours or 0 hours to 8 hours (one dosing interval in steady state)
Secondary outcome [4] 0 0
Ctrough,ss in Plasma
Timepoint [4] 0 0
0 hours to 24 hours, 0 hours to 12 hours or 0 hours to 8 hours(one sampling interval in steady state)
Secondary outcome [5] 0 0
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years
Timepoint [5] 0 0
Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60
Secondary outcome [6] 0 0
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years
Timepoint [6] 0 0
Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60
Secondary outcome [7] 0 0
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years
Timepoint [7] 0 0
Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60
Secondary outcome [8] 0 0
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years
Timepoint [8] 0 0
Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60
Secondary outcome [9] 0 0
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years
Timepoint [9] 0 0
Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60
Secondary outcome [10] 0 0
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years
Timepoint [10] 0 0
Up to 3 hours post dose on Day30, and up to 6 hours post dose on Day 60
Secondary outcome [11] 0 0
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years
Timepoint [11] 0 0
Up to 3 hours post dose on Day30, and up to 6 hours post dose on Day 60
Secondary outcome [12] 0 0
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years
Timepoint [12] 0 0
Up to 3 hours post dose on Day30, and up to 6 hours post dose on Day 60
Secondary outcome [13] 0 0
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years
Timepoint [13] 0 0
Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Secondary outcome [14] 0 0
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years
Timepoint [14] 0 0
Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Secondary outcome [15] 0 0
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years
Timepoint [15] 0 0
Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Secondary outcome [16] 0 0
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years
Timepoint [16] 0 0
Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Secondary outcome [17] 0 0
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years
Timepoint [17] 0 0
Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Secondary outcome [18] 0 0
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years
Timepoint [18] 0 0
Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60
Secondary outcome [19] 0 0
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years
Timepoint [19] 0 0
Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60
Secondary outcome [20] 0 0
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years
Timepoint [20] 0 0
Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60
Secondary outcome [21] 0 0
Anti-Xa Values: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years
Timepoint [21] 0 0
Up to 4 hours post dose on Day 30, up to 8 hours post dose on Day 60, and up to 24 hours on Day 90
Secondary outcome [22] 0 0
Anti-Xa Values: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years
Timepoint [22] 0 0
Up to 4 hours post dose on Day 30, up to 8 hours post dose on Day 60, and up to 24 hours on Day 90
Secondary outcome [23] 0 0
Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years
Timepoint [23] 0 0
Up to 4 hours post dose on Day 30, up to 8 hours post dose on Day 60, and up to 16 hours on Day 90
Secondary outcome [24] 0 0
Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years
Timepoint [24] 0 0
Up to 4 hours post dose on Day 30, up to 8 hours post dose on Day 60, and up to 16 hours on Day 90
Secondary outcome [25] 0 0
Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years
Timepoint [25] 0 0
Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Secondary outcome [26] 0 0
Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years
Timepoint [26] 0 0
Up to 3 hours post dose on Day 30, up to 6 hours post dose on Day 60, and up to 16 hours on Day 90
Secondary outcome [27] 0 0
Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years
Timepoint [27] 0 0
Up to 3 hours post dose on Day 30, up to 6 hours post dose on Day 60, up to 16 hours on Day 90 and follow-up up to 30 days
Secondary outcome [28] 0 0
Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years
Timepoint [28] 0 0
Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60

Eligibility
Key inclusion criteria
* Children aged birth to < 18 years with confirmed venous thromboembolism who receive initial treatment with therapeutic dosages of UFH (unfractionated heparin), LMWH (low molecular weight heparin) or fondaparinux and require anticoagulant therapy for at least 90 days. However, children aged birth to < 2 years with catheter-related thrombosis require anticoagulant therapy for at least 30 days.
* For children younger than 6 months:

* Gestational age at birth of at least 37 weeks.
* Oral feeding/nasogastric/gastric feeding for at least 10 days.
* Body weight =2600 g
Minimum age
No limit
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Active bleeding or bleeding risk contraindicating anticoagulant therapy
* An estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m*2 (in children younger than 1 year, serum creatinine results above 97.5th percentile excludes participation)
* Hepatic disease which is associated with either: 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 109/L
* Sustained uncontrolled 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), including but not limited to 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, including but not limited to rifampicin, rifabutin, phenobarbital, phenytoin and carbamazepine
* Childbearing potential without proper contraceptive measures, pregnancy or breast feeding

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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 3
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)
VIC
Recruitment hospital [1] 0 0
- Parkville
Recruitment hospital [2] 0 0
- South Brisbane
Recruitment postcode(s) [1] 0 0
3052 - Parkville
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
Argentina
State/province [14] 0 0
Tucuman
Country [15] 0 0
Austria
State/province [15] 0 0
Oberösterreich
Country [16] 0 0
Austria
State/province [16] 0 0
Steiermark
Country [17] 0 0
Austria
State/province [17] 0 0
Tirol
Country [18] 0 0
Austria
State/province [18] 0 0
Wien
Country [19] 0 0
Belgium
State/province [19] 0 0
Bruxelles - Brussel
Country [20] 0 0
Belgium
State/province [20] 0 0
Edegem
Country [21] 0 0
Belgium
State/province [21] 0 0
Leuven
Country [22] 0 0
Brazil
State/province [22] 0 0
Sao Paulo
Country [23] 0 0
Canada
State/province [23] 0 0
Alberta
Country [24] 0 0
Canada
State/province [24] 0 0
Ontario
Country [25] 0 0
Canada
State/province [25] 0 0
Quebec
Country [26] 0 0
China
State/province [26] 0 0
Zhejiang
Country [27] 0 0
China
State/province [27] 0 0
Beijing
Country [28] 0 0
China
State/province [28] 0 0
Shanghai
Country [29] 0 0
Finland
State/province [29] 0 0
Turku
Country [30] 0 0
France
State/province [30] 0 0
Montpellier
Country [31] 0 0
France
State/province [31] 0 0
Paris
Country [32] 0 0
France
State/province [32] 0 0
TOULOUSE Cedex 9
Country [33] 0 0
Germany
State/province [33] 0 0
Bayern
Country [34] 0 0
Germany
State/province [34] 0 0
Sachsen-Anhalt
Country [35] 0 0
Germany
State/province [35] 0 0
Sachsen
Country [36] 0 0
Germany
State/province [36] 0 0
Berlin
Country [37] 0 0
Hong Kong
State/province [37] 0 0
Hong Kong
Country [38] 0 0
Hungary
State/province [38] 0 0
Budapest
Country [39] 0 0
Ireland
State/province [39] 0 0
Dublin
Country [40] 0 0
Israel
State/province [40] 0 0
Afula
Country [41] 0 0
Israel
State/province [41] 0 0
Jerusalem
Country [42] 0 0
Israel
State/province [42] 0 0
Petach Tikva
Country [43] 0 0
Israel
State/province [43] 0 0
Ramat Gan
Country [44] 0 0
Italy
State/province [44] 0 0
Lombardia
Country [45] 0 0
Italy
State/province [45] 0 0
Piemonte
Country [46] 0 0
Italy
State/province [46] 0 0
Veneto
Country [47] 0 0
Japan
State/province [47] 0 0
Aichi
Country [48] 0 0
Japan
State/province [48] 0 0
Nagano
Country [49] 0 0
Japan
State/province [49] 0 0
Tokyo
Country [50] 0 0
Mexico
State/province [50] 0 0
Distrito Federal
Country [51] 0 0
Mexico
State/province [51] 0 0
Jalisco
Country [52] 0 0
Netherlands
State/province [52] 0 0
Amsterdam
Country [53] 0 0
Netherlands
State/province [53] 0 0
Groningen
Country [54] 0 0
Netherlands
State/province [54] 0 0
Nijmegen
Country [55] 0 0
Netherlands
State/province [55] 0 0
Rotterdam
Country [56] 0 0
Netherlands
State/province [56] 0 0
Utrecht
Country [57] 0 0
Portugal
State/province [57] 0 0
Lisboa
Country [58] 0 0
Russian Federation
State/province [58] 0 0
Kazan
Country [59] 0 0
Russian Federation
State/province [59] 0 0
Kemerovo
Country [60] 0 0
Russian Federation
State/province [60] 0 0
Krasnodar
Country [61] 0 0
Russian Federation
State/province [61] 0 0
Moscow
Country [62] 0 0
Russian Federation
State/province [62] 0 0
Nizhny Novgorod
Country [63] 0 0
Russian Federation
State/province [63] 0 0
Sankt-Peterburg
Country [64] 0 0
Russian Federation
State/province [64] 0 0
St. Petersburg
Country [65] 0 0
Russian Federation
State/province [65] 0 0
Volgograd
Country [66] 0 0
Russian Federation
State/province [66] 0 0
Yekaterinburg
Country [67] 0 0
Singapore
State/province [67] 0 0
Singapore
Country [68] 0 0
Slovakia
State/province [68] 0 0
Bratislava
Country [69] 0 0
Spain
State/province [69] 0 0
Barcelona
Country [70] 0 0
Spain
State/province [70] 0 0
A Coruña
Country [71] 0 0
Sweden
State/province [71] 0 0
Solna
Country [72] 0 0
Switzerland
State/province [72] 0 0
Bern
Country [73] 0 0
Switzerland
State/province [73] 0 0
Luzern
Country [74] 0 0
Switzerland
State/province [74] 0 0
Zürich
Country [75] 0 0
Turkey
State/province [75] 0 0
Adana
Country [76] 0 0
Turkey
State/province [76] 0 0
Istanbul
Country [77] 0 0
Turkey
State/province [77] 0 0
Konya
Country [78] 0 0
United Kingdom
State/province [78] 0 0
Tyne And Wear
Country [79] 0 0
United Kingdom
State/province [79] 0 0
West Midlands
Country [80] 0 0
United Kingdom
State/province [80] 0 0
West Yorkshire
Country [81] 0 0
United Kingdom
State/province [81] 0 0
Cardiff
Country [82] 0 0
United Kingdom
State/province [82] 0 0
Edinburgh
Country [83] 0 0
United Kingdom
State/province [83] 0 0
Glasgow
Country [84] 0 0
United Kingdom
State/province [84] 0 0
London
Country [85] 0 0
United Kingdom
State/province [85] 0 0
Manchester
Country [86] 0 0
United Kingdom
State/province [86] 0 0
Oxford
Country [87] 0 0
United Kingdom
State/province [87] 0 0
Sheffield

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
Trial website
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.