EINSTEIN Junior: Oral Rivaroxaban in Children With Venous Thrombosis

NCT ID: NCT02234843

Last Updated: 2020-04-01

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

500 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-11-13

Study Completion Date

2019-01-30

Brief Summary

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

Detailed Description

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Conditions

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Venous Thromboembolism

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Rivaroxaban (Xarelto, BAY59-7939)

Intervention Type DRUG

Age and body weight-adjusted dosing equivalent to 20 mg rivaroxaban in adults, once daily or twice daily, as tablets

Rivaroxaban (Xarelto, BAY59-7939)

Intervention Type DRUG

Age and body weight-adjusted dosing equivalent to 20 mg rivaroxaban in adults, once daily, twice daily or three times daily, as oral suspension

Standard of Care

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

Group Type EXPERIMENTAL

Standard of Care

Intervention Type DRUG

LMWH (low molecular weight heparin) or fondaparinux or vitamin K antagonist (VKA) therapy.

dose : as per standard of care

Interventions

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Rivaroxaban (Xarelto, BAY59-7939)

Age and body weight-adjusted dosing equivalent to 20 mg rivaroxaban in adults, once daily or twice daily, as tablets

Intervention Type 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

Intervention Type DRUG

Standard of Care

LMWH (low molecular weight heparin) or fondaparinux or vitamin K antagonist (VKA) therapy.

dose : as per standard of care

Intervention Type DRUG

Eligibility Criteria

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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
Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Janssen Research & Development, LLC

INDUSTRY

Sponsor Role collaborator

Bayer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

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Phoenix, Arizona, United States

Site Status

Little Rock, Arkansas, United States

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Los Angeles, California, United States

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Los Angeles, California, United States

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San Diego, California, United States

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Gainesville, Florida, United States

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Jacksonville, Florida, United States

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Miami, Florida, United States

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Pensacola, Florida, United States

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St. Petersburg, Florida, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Indianapolis, Indiana, United States

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Lansing, Michigan, United States

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Kansas City, Missouri, United States

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Durham, North Carolina, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Columbus, Ohio, United States

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Philadelphia, Pennsylvania, United States

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Dallas, Texas, United States

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Fort Worth, Texas, United States

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Houston, Texas, United States

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San Miguel de Tucumán, Tucumán Province, Argentina

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Parkville, Victoria, Australia

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South Brisbane, , Australia

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Graz, Styria, Austria

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Innsbruck, Tyrol, Austria

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Linz, Upper Austria, Austria

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Vienna, , Austria

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Bruxelles - Brussel, , Belgium

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Edegem, , Belgium

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Leuven, , Belgium

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Campinas, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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Calgary, Alberta, Canada

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Edmonton, Alberta, Canada

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Hamilton, Ontario, Canada

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Ottawa, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Hangzhou, Zhejiang, China

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Beijing, , China

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Beijing, , China

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Shanghai, , China

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Turku, , Finland

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Montpellier, , France

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Paris, , France

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Toulouse, , France

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Erlangen, Bavaria, Germany

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Dresden, Saxony, Germany

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Halle, Saxony-Anhalt, Germany

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Berlin, , Germany

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Hong Kong, , Hong Kong

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Budapest, , Hungary

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Crumlin, Dublin, Ireland

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Afula, , Israel

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Jerusalem, , Israel

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Petah Tikva, , Israel

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Ramat Gan, , Israel

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Milan, Lombardy, Italy

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Turin, Piedmont, Italy

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Padua, Veneto, Italy

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Ōbu, Aichi-ken, Japan

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Azumino, Nagano, Japan

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Bunkyo-ku, Tokyo, Japan

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Guadalajara, Jalisco, Mexico

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Mexico City, Mexico City, Mexico

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Amsterdam, , Netherlands

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Groningen, , Netherlands

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Nijmegen, , Netherlands

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Rotterdam, , Netherlands

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Utrecht, , Netherlands

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Carnaxide, Lisbon District, Portugal

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Kazan', , Russia

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Kemerovo, , Russia

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Krasnodar, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Nizhny Novgorod, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Volgograd, , Russia

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Yekaterinburg, , Russia

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Singapore, , Singapore

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Singapore, , Singapore

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Bratislava, , Slovakia

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Esplugues de Llobregat, Barcelona, Spain

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A Coruña, , Spain

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Barcelona, , Spain

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Solna, , Sweden

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Bern, , Switzerland

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Lucerne, , Switzerland

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Zurich, , Switzerland

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Adana, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Konya, , Turkey (Türkiye)

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Newcastle upon Tyne, Tyne and Wear, United Kingdom

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Birmingham, West Midlands, United Kingdom

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Leeds, West Yorkshire, United Kingdom

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Cardiff, , United Kingdom

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Edinburgh, , United Kingdom

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Glasgow, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Oxford, , United Kingdom

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Sheffield, , United Kingdom

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Countries

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United States Argentina Australia Austria Belgium Brazil Canada China Finland France Germany Hong Kong Hungary Ireland Israel Italy Japan Mexico Netherlands Portugal Russia Singapore Slovakia Spain Sweden Switzerland Turkey (Türkiye) United Kingdom

References

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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.

Reference Type DERIVED
PMID: 36006613 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33351120 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33002131 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31699660 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31420317 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30598642 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2014-000565-47

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

14372

Identifier Type: -

Identifier Source: org_study_id

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