EINSTEIN Junior: Oral Rivaroxaban in Children With Venous Thrombosis (EINSTEIN Jr)

• ClinicalTrials.gov Identifier: NCT02234843
• Recruitment Status: Completed
• First Posted: September 9, 2014
• Results First Posted: April 1, 2020
• Last Update Posted: April 1, 2020
• Sponsor: Bayer
• Collaborator: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Bayer

Study Description

Brief Summary:

The purpose of this study is to evaluate comparative efficacy and safety of rivaroxaban to standard of care in children with acute venous thromboembolism.

Condition or disease	Intervention/treatment	Phase
Venous Thromboembolism	Drug: Rivaroxaban (Xarelto, BAY59-7939); Drug: Standard of Care	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 500 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official 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
• Actual Study Start Date: November 13, 2014
• Actual Primary Completion Date: January 30, 2019
• Actual Study Completion Date: January 30, 2019

Arms and Interventions

Arm	Intervention/treatment
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.	Drug: Rivaroxaban (Xarelto, BAY59-7939); Age and body weight-adjusted dosing equivalent to 20 mg rivaroxaban in adults, once daily or twice daily, as tablets; Drug: 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
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	Drug: Standard of Care; LMWH (low molecular weight heparin) or fondaparinux or vitamin K antagonist (VKA) therapy. dose : as per standard of care

Outcome Measures

Primary Outcome Measures :

1. Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period [ Time Frame: 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) ]
   The Central independent adjudication committee (CIAC) classified symptomatic recurrent venous thromboembolism (VTE). Incidence = number of events / number at risk, where: number of events = number of subjects having the event in the time window. number at risk = number of subjects in reference population
2. Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period [ Time Frame: 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) ]
   The Central independent adjudication committee (CIAC) classified symptomatic recurrent venous thromboembolism (VTE). Incidence = number of events / number at risk, where: number of events = number of subjects having the event in the time window. number at risk = number of subjects in reference population
3. Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period [ Time Frame: During extended treatment period: up to month 12. ]
   Incidence rates for all children except those aged < 2 years with catheter-related thrombosis. If no participant in the specific subgroup entered in the specific optional extension period, no analysis of an outcome was possible., The Central independent adjudication committee (CIAC) classified symptomatic recurrent venous thromboembolism (VTE). Incidence = number of events / number at risk, where: number of events = number of subjects having the event in the time window. number at risk = number of subjects in reference Population.
4. 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) [ Time Frame: More than 2 and up to 30 days after stop of study medication ]
   The Central independent adjudication committee (CIAC) classified symptomatic recurrent venous thromboembolism (VTE). Age group with primary efficacy outcome was reported.
5. Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Main Treatment Period [ Time Frame: 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) ]
   The Central independent adjudication committee (CIAC) classified bleeding as: Major bleeding defined as overt bleeding and: · associated with a fall in hemoglobin of 2 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, intraarticular, intramuscular with compartment syndrome, retroperitoneal, or contributing to death. Clinically relevant non-major bleeding 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 (temporary) cessation 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).
6. Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period [ Time Frame: During extended treatment period: up to month 12. ]
   Incidence rates for all children except those aged < 2 years with catheter-related thrombosis. If no participant entered in the specific optional extension period, no analysis of an outcome was possible. The CIAC classified bleeding as: Major bleeding defined as overt bleeding and: associated with a fall in hemoglobin of 2 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, intraarticular, intramuscular with compartment syndrome, retroperitoneal, or contributing to death. Clinically relevant non-major bleeding defined as overt bleeding not meeting the criteria for major bleeding, but associated with: medical intervention, or unscheduled contact with a physician, or (temporary) cessation of study treatment, or discomfort for the child such as pain or impairment of activities of daily life.

Secondary Outcome Measures :

1. 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 [ Time Frame: 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) ]
   The secondary efficacy outcome defined as the composite of all symptomatic recurrent venous thromboembolism and asymptomatic deterioration on repeat imaging as assessed by central independent adjudication committee. (CIAC) Incidence = number of events / number at risk, where: number of events = number of subjects having the event in the time window. number at risk = number of subjects in reference population
2. AUC(0-24)ss in Plasma [ Time Frame: over 24 hours ]
   AUC(0-24)ss: Area under the concentration vs. time curve from time 0 to 24 hours at steady state.
3. Cmax,ss in Plasma [ Time Frame: 0 hours to 24 hours, 0 hours to 12 hours or 0 hours to 8 hours (one dosing interval in steady state) ]
   Maximum drug concentration in measured matrix at steady state during a dosage interval
4. Ctrough,ss in Plasma [ Time Frame: 0 hours to 24 hours, 0 hours to 12 hours or 0 hours to 8 hours(one sampling interval in steady state) ]
   Ctrough,ss refers to the drug concentration at the end of the dosage interval at steady state
5. Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years [ Time Frame: Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60 ]
   Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds.
6. Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years [ Time Frame: Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60 ]
   Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds.
7. Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years [ Time Frame: Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60 ]
   Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds.
8. Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years [ Time Frame: Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60 ]
   Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds. 'NA' denotes the data that cannot be calculated.
9. Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years [ Time Frame: Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60 ]
   Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds. 'NA' denotes the data that cannot be calculated.
10. Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years [ Time Frame: Up to 3 hours post dose on Day30, and up to 6 hours post dose on Day 60 ]
    Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds.
11. Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years [ Time Frame: Up to 3 hours post dose on Day30, and up to 6 hours post dose on Day 60 ]
    Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds.
12. Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years [ Time Frame: Up to 3 hours post dose on Day30, and up to 6 hours post dose on Day 60 ]
    Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds.
13. Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years [ Time Frame: Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60 ]
    The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds.
14. Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years [ Time Frame: Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60 ]
    The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds.
15. Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years [ Time Frame: Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60 ]
    The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds.
16. Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years [ Time Frame: Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60 ]
    The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds. 'NA' denotes the data that cannot be calculated.
17. Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years [ Time Frame: Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60 ]
    The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds. 'NA' denotes the data that cannot be calculated.
18. Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years [ Time Frame: Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60 ]
    The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds.
19. Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years [ Time Frame: Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60 ]
    The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds.
20. Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years [ Time Frame: Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60 ]
    The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds.
21. Anti-Xa Values: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years [ Time Frame: 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 ]
    This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method.
22. Anti-Xa Values: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years [ Time Frame: 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 ]
    This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method.
23. Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years [ Time Frame: 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 ]
    This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method.
24. Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years [ Time Frame: 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 ]
    This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method.
25. Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years [ Time Frame: Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60 ]
    This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method. 'NA' denotes the data that cannot be calculated.
26. Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years [ Time Frame: 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 ]
    This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method. 'NA' denotes the data that cannot be calculated.
27. Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years [ Time Frame: 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 ]
    This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method. 'NA' denotes the data that cannot be calculated.
28. Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years [ Time Frame: Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60 ]
    This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method.

Eligibility Criteria

• Ages Eligible for Study: up to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

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

Contacts and Locations

Locations

United States, Arizona

Phoenix, Arizona, United States, 85016

United States, Arkansas

Little Rock, Arkansas, United States, 72202-3500

United States, California

Los Angeles, California, United States, 90027-6089

Los Angeles, California, United States, 90095

San Diego, California, United States, 92123

United States, Florida

Gainesville, Florida, United States, 32610

Jacksonville, Florida, United States, 32207

Miami, Florida, United States, 33155

Pensacola, Florida, United States, 32504

Saint Petersburg, Florida, United States, 33701

United States, Georgia

Atlanta, Georgia, United States, 30322

United States, Illinois

Chicago, Illinois, United States, 60611

United States, Indiana

Indianapolis, Indiana, United States, 46202

United States, Michigan

Lansing, Michigan, United States, 48912

United States, Missouri

Kansas City, Missouri, United States, 64108-9898

United States, North Carolina

Durham, North Carolina, United States, 27710

United States, Ohio

Cincinnati, Ohio, United States, 45229-3039

Cleveland, Ohio, United States, 44106-2602

Columbus, Ohio, United States, 43205-2696

United States, Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

United States, Texas

Dallas, Texas, United States, 75235

Fort Worth, Texas, United States, 76104

Houston, Texas, United States, 77030

Argentina

San Miguel de Tucumán, Tucuman, Argentina, 4000

Australia, Victoria

Parkville, Victoria, Australia, 3052

Australia

South Brisbane, Australia, 4101

Austria

Linz, Oberösterreich, Austria, 4020

Graz, Steiermark, Austria, 8036

Innsbruck, Tirol, Austria, 6020

Wien, Austria, 1090

Belgium

Bruxelles - Brussel, Belgium, 1200

Edegem, Belgium, 2650

Leuven, Belgium, 3000

Brazil

Campinas, Sao Paulo, Brazil, 13083-970

São Paulo, Sao Paulo, Brazil, 01227-200

Sao Paulo, Brazil, 04023-061

Sao Paulo, Brazil, 05403-000

Canada, Alberta

Calgary, Alberta, Canada, T3B 6A8

Edmonton, Alberta, Canada, T6G 2B7

Canada, Ontario

Hamilton, Ontario, Canada, L8N 3Z5

Ottawa, Ontario, Canada, K1H 8L1

Toronto, Ontario, Canada, M5G 1X8

Canada, Quebec

Montreal, Quebec, Canada, H4A 3J1

China, Zhejiang

Hangzhou, Zhejiang, China

China

Beijing, China, 100034

Beijing, China, 100045

Shanghai, China

Finland

Turku, Finland, 20520

France

Montpellier, France, 34059

Paris, France, 75015

TOULOUSE Cedex 9, France, 31059

Germany

Erlangen, Bayern, Germany, 91054

Halle, Sachsen-Anhalt, Germany, 06120

Dresden, Sachsen, Germany, 01307

Berlin, Germany, 13353

Hong Kong

Hong Kong, Hong Kong

Hungary

Budapest, Hungary, 1097

Ireland

Crumlin, Dublin, Ireland, 12

Israel

Afula, Israel, 1834111

Jerusalem, Israel, 9112001

Petach Tikva, Israel, 4920235

Ramat Gan, Israel, 5262000

Italy

Milano, Lombardia, Italy, 20122

Torino, Piemonte, Italy, 10126

Padova, Veneto, Italy, 35128

Japan

Obu, Aichi, Japan, 474-8710

Azumino, Nagano, Japan, 399-8288

Bunkyo-ku, Tokyo, Japan, 113-8655

Mexico

Ciudad de México, Distrito Federal, Mexico, 06720

Guadalajara, Jalisco, Mexico

Netherlands

Amsterdam, Netherlands, 1105 AZ

Groningen, Netherlands, 9713 GZ

Nijmegen, Netherlands, 6525 GA

Rotterdam, Netherlands, 3015 CE

Utrecht, Netherlands, 3584 CX

Portugal

Carnaxide, Lisboa, Portugal, 2795-53

Russian Federation

Kazan, Russian Federation, 420138

Kemerovo, Russian Federation, 650002

Krasnodar, Russian Federation, 350013

Moscow, Russian Federation, 117997

Moscow, Russian Federation, 119049

Nizhny Novgorod, Russian Federation, 603136

Sankt-Peterburg, Russian Federation, 197110

St. Petersburg, Russian Federation, 197022

Volgograd, Russian Federation, 400138

Yekaterinburg, Russian Federation, 620028

Singapore

Singapore, Singapore, 119228

Singapore, Singapore, 229 899

Slovakia

Bratislava, Slovakia, 833 41

Spain

Esplugues de LLobregat, Barcelona, Spain, 08950

A Coruña, Spain, 15006

Barcelona, Spain, 08035

Sweden

Solna, Sweden, 171 64

Switzerland

Bern, Switzerland, 3010

Luzern, Switzerland, 6000

Zürich, Switzerland, 8032

Turkey

Adana, Turkey, 01130

Istanbul, Turkey, 34093

Konya, Turkey, 42080

United Kingdom

Newcastle Upon Tyne, Tyne And Wear, United Kingdom, NE1 4LP

Birmingham, West Midlands, United Kingdom, B4 6NH

Leeds, West Yorkshire, United Kingdom, LS1 3EX

Cardiff, United Kingdom, CF14 4XW

Edinburgh, United Kingdom, EH9 1LF

Glasgow, United Kingdom, G51 4TF

London, United Kingdom, SW3 6NP

Manchester, United Kingdom, M13 9WL

Oxford, United Kingdom, OX3 9DU

Sheffield, United Kingdom, S10 2TH

Sponsors and Collaborators

Bayer

Janssen Research & Development, LLC

Investigators

• Study Director: Bayer Study Director; Bayer

  Study Documents (Full-Text)

Documents provided by Bayer:

Study Protocol  [PDF] September 27, 2017

Statistical Analysis Plan  [PDF] March 1, 2019

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Palumbo JS, Lensing AWA, Brandao LR, Hooimeijer HL, Kenet G, van Ommen H, Pap AF, Majumder M, Kubitza D, Thelen K, Willmann S, Prins MH, Monagle P, Male C. Anticoagulation in pediatric cancer-associated venous thromboembolism: a subgroup analysis of EINSTEIN-Jr. Blood Adv. 2022 Nov 22;6(22):5821-5828. doi: 10.1182/bloodadvances.2022008160.

Connor P, Sanchez van Kammen M, Lensing AWA, Chalmers E, Kallay K, Hege K, Simioni P, Biss T, Bajolle F, Bonnet D, Grunt S, Kumar R, Lvova O, Bhat R, Van Damme A, Palumbo J, Santamaria A, Saracco P, Payne J, Baird S, Godder K, Labarque V, Male C, Martinelli I, Morales Soto M, Motwani J, Shah S, Hooimeijer HL, Prins MH, Kubitza D, Smith WT, Berkowitz SD, Pap AF, Majumder M, Monagle P, Coutinho JM. Safety and efficacy of rivaroxaban in pediatric cerebral venous thrombosis (EINSTEIN-Jr CVT). Blood Adv. 2020 Dec 22;4(24):6250-6258. doi: 10.1182/bloodadvances.2020003244.

Thom K, Lensing AWA, Nurmeev I, Bajolle F, Bonnet D, Kenet G, Massicotte MP, Karakas Z, Palumbo JS, Saracco P, Amedro P, Chain J, Chan AK, Ikeyama T, Lam JCM, Gauger C, Pap AF, Majumder M, Kubitza D, Smith WT, Berkowitz SD, Prins MH, Monagle P, Young G, Male C. Safety and efficacy of anticoagulant therapy in pediatric catheter-related venous thrombosis (EINSTEIN-Jr CVC-VTE). Blood Adv. 2020 Oct 13;4(19):4632-4639. doi: 10.1182/bloodadvances.2020002637.

Male C, Lensing AWA, Palumbo JS, Kumar R, Nurmeev I, Hege K, Bonnet D, Connor P, Hooimeijer HL, Torres M, Chan AKC, Kenet G, Holzhauer S, Santamaria A, Amedro P, Chalmers E, Simioni P, Bhat RV, Yee DL, Lvova O, Beyer-Westendorf J, Biss TT, Martinelli I, Saracco P, Peters M, Kallay K, Gauger CA, Massicotte MP, Young G, Pap AF, Majumder M, Smith WT, Heubach JF, Berkowitz SD, Thelen K, Kubitza D, Crowther M, Prins MH, Monagle P; EINSTEIN-Jr Phase 3 Investigators. Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial. Lancet Haematol. 2020 Jan;7(1):e18-e27. doi: 10.1016/S2352-3026(19)30219-4. Epub 2019 Nov 5.

Monagle P, Lensing AWA, Thelen K, Martinelli I, Male C, Santamaria A, Samochatova E, Kumar R, Holzhauer S, Saracco P, Simioni P, Robertson J, Grangl G, Halton J, Connor P, Young G, Molinari AC, Nowak-Gottl U, Kenet G, Kapsa S, Willmann S, Pap AF, Becka M, Twomey T, Beyer-Westendorf J, Prins MH, Kubitza D; EINSTEIN-Jr Phase 2 Investigators. Bodyweight-adjusted rivaroxaban for children with venous thromboembolism (EINSTEIN-Jr): results from three multicentre, single-arm, phase 2 studies. Lancet Haematol. 2019 Oct;6(10):e500-e509. doi: 10.1016/S2352-3026(19)30161-9. Epub 2019 Aug 13.

Lensing AWA, Male C, Young G, Kubitza D, Kenet G, Patricia Massicotte M, Chan A, Molinari AC, Nowak-Goettl U, Pap AF, Adalbo I, Smith WT, Mason A, Thelen K, Berkowitz SD, Crowther M, Schmidt S, Price V, Prins MH, Monagle P. Rivaroxaban versus standard anticoagulation for acute venous thromboembolism in childhood. Design of the EINSTEIN-Jr phase III study. Thromb J. 2018 Dec 21;16:34. doi: 10.1186/s12959-018-0188-y. eCollection 2018.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT02234843
• Other Study ID Numbers: 14372; 2014-000565-47 ( EudraCT Number )
• First Posted: September 9, 2014
• Results First Posted: April 1, 2020
• Last Update Posted: April 1, 2020
• Last Verified: March 2020

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

Keywords provided by Bayer:

Pediatric

Additional relevant MeSH terms:

Thromboembolism; Venous Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Rivaroxaban; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anticoagulants