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

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

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

Study Overview

• Status: Completed
• Conditions: Venous Thromboembolism
• Intervention / Treatment: Drug: Rivaroxaban (Xarelto, BAY59-7939); Drug: Rivaroxaban (Xarelto, BAY59-7939); Drug: Standard of Care

• Study Type: Interventional
• Enrollment (Actual): 500
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Tucuman
    • San Miguel de Tucumán, Tucuman, Argentina, 4000
• Australia
  • South Brisbane, Australia, 4101
  • Victoria
    • Parkville, Victoria, Australia, 3052
• Austria
  • Wien, Austria, 1090
  • Oberösterreich
    • Linz, Oberösterreich, Austria, 4020
  • Steiermark
    • Graz, Steiermark, Austria, 8036
  • Tirol
    • Innsbruck, Tirol, Austria, 6020
• Belgium
  • Bruxelles - Brussel, Belgium, 1200
  • Edegem, Belgium, 2650
  • Leuven, Belgium, 3000
• Brazil
  • Sao Paulo, Brazil, 05403-000
  • Sao Paulo, Brazil, 04023-061
  • Sao Paulo
    • Campinas, Sao Paulo, Brazil, 13083-970
    • São Paulo, Sao Paulo, Brazil, 01227-200
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
    • Edmonton, Alberta, Canada, T6G 2B7
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
    • Ottawa, Ontario, Canada, K1H 8L1
    • Toronto, Ontario, Canada, M5G 1X8
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
• China
  • Beijing, China, 100034
  • Beijing, China, 100045
  • Shanghai, China
  • Zhejiang
    • Hangzhou, Zhejiang, China
• Finland
  • Turku, Finland, 20520
• France
  • Montpellier, France, 34059
  • Paris, France, 75015
  • TOULOUSE Cedex 9, France, 31059
• Germany
  • Berlin, Germany, 13353
  • Bayern
    • Erlangen, Bayern, Germany, 91054
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
  • Sachsen-Anhalt
    • Halle, Sachsen-Anhalt, Germany, 06120
• Hong Kong
  • Hong Kong, Hong Kong
• Hungary
  • Budapest, Hungary, 1097
• Ireland
  • Dublin
    • Crumlin, Dublin, Ireland, 12
• Israel
  • Afula, Israel, 1834111
  • Jerusalem, Israel, 9112001
  • Petach Tikva, Israel, 4920235
  • Ramat Gan, Israel, 5262000
• Italy
  • Lombardia
    • Milano, Lombardia, Italy, 20122
  • Piemonte
    • Torino, Piemonte, Italy, 10126
  • Veneto
    • Padova, Veneto, Italy, 35128
• Japan
  • Aichi
    • Obu, Aichi, Japan, 474-8710
  • Nagano
    • Azumino, Nagano, Japan, 399-8288
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8655
• Mexico
  • Distrito Federal
    • Ciudad de México, Distrito Federal, Mexico, 06720
  • Jalisco
    • 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
  • Lisboa
    • Carnaxide, Lisboa, Portugal, 2795-53
• Russian Federation
  • Kazan, Russian Federation, 420138
  • Kemerovo, Russian Federation, 650002
  • Krasnodar, Russian Federation, 350013
  • Moscow, Russian Federation, 119049
  • Moscow, Russian Federation, 117997
  • 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
  • A Coruña, Spain, 15006
  • Barcelona, Spain, 08035
  • Barcelona
    • Esplugues de LLobregat, Barcelona, Spain, 08950
• 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
  • 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
  • Tyne And Wear
    • Newcastle Upon Tyne, Tyne And Wear, United Kingdom, NE1 4LP
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B4 6NH
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS1 3EX
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
  • Arkansas
    • Little Rock, Arkansas, United States, 72202-3500
  • California
    • Los Angeles, California, United States, 90095
    • Los Angeles, California, United States, 90027-6089
    • San Diego, California, United States, 92123
  • 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
  • Georgia
    • Atlanta, Georgia, United States, 30322
  • Illinois
    • Chicago, Illinois, United States, 60611
  • Indiana
    • Indianapolis, Indiana, United States, 46202
  • Michigan
    • Lansing, Michigan, United States, 48912
  • Missouri
    • Kansas City, Missouri, United States, 64108-9898
  • North Carolina
    • Durham, North Carolina, United States, 27710
  • Ohio
    • Cincinnati, Ohio, United States, 45229-3039
    • Cleveland, Ohio, United States, 44106-2602
    • Columbus, Ohio, United States, 43205-2696
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
  • Texas
    • Dallas, Texas, United States, 75235
    • Fort Worth, Texas, United States, 76104
    • Houston, Texas, United States, 77030

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 13 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period	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	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)
Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period	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	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)
Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period	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.	During extended treatment period: up to month 12.
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)	The Central independent adjudication committee (CIAC) classified symptomatic recurrent venous thromboembolism (VTE). Age group with primary efficacy outcome was reported.	More than 2 and up to 30 days after stop of study medication
Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Main Treatment Period	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).	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)
Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period	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.	During extended treatment period: up to month 12.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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)
AUC(0-24)ss in Plasma	AUC(0-24)ss: Area under the concentration vs. time curve from time 0 to 24 hours at steady state.	over 24 hours
Cmax,ss in Plasma	Maximum drug concentration in measured matrix at steady state during a dosage interval	0 hours to 24 hours, 0 hours to 12 hours or 0 hours to 8 hours (one dosing interval in steady state)
Ctrough,ss in Plasma	Ctrough,ss refers to the drug concentration at the end of the dosage interval at steady state	0 hours to 24 hours, 0 hours to 12 hours or 0 hours to 8 hours(one sampling interval in steady state)
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years	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.	Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years	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.	Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years	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.	Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years	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.	Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years	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.	Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years	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.	Up to 3 hours post dose on Day30, and up to 6 hours post dose on Day 60
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years	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.	Up to 3 hours post dose on Day30, and up to 6 hours post dose on Day 60
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years	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.	Up to 3 hours post dose on Day30, and up to 6 hours post dose on Day 60
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years	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.	Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years	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.	Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years	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.	Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years	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.	Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years	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.	Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years	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.	Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years	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.	Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years	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.	Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60
Anti-Xa Values: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years	This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method.	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
Anti-Xa Values: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years	This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method.	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
Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years	This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method.	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
Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years	This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method.	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
Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years	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.	Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years	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.	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
Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years	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.	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
Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years	This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method.	Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Janssen Research & Development, LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2014
• Primary Completion (Actual): January 30, 2019
• Study Completion (Actual): January 30, 2019

Study Registration Dates

• First Submitted: September 5, 2014
• First Submitted That Met QC Criteria: September 5, 2014
• First Posted (Estimate): September 9, 2014

Study Record Updates

• Last Update Posted (Actual): April 1, 2020
• Last Update Submitted That Met QC Criteria: March 13, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Pediatric
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thromboembolism; Venous Thromboembolism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban
• Other Study ID Numbers: 14372; 2014-000565-47 (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