EINSTEIN Junior Phase II: Oral Rivaroxaban in Young Children With Venous Thrombosis

NCT02309411 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 143742014-000566-22
• Study Type: interventional
• Target: 46
• Locations: 14 countries
• Sites: 28

Brief Summary

The purpose of this study is to find out whether rivaroxaban is safe to use in children and how long it stays in the body. Safety will be assessed by looking at the incidence and types of bleeding events. There will also be a check for worsening of blood clots.

Conditions

Venous Thromboembolism

Keywords

Pediatric

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Major Bleeding and Clinically Relevant Non-Major Bleeding Events

  Major bleeding is defined as overt bleeding and: * associated with a fall in hemoglobin of 2 gram/decilitre (g/dL) or more, or * leading to a transfusion of the equivalent of 2 or more units of packed red blood cells or whole blood in adults, or * occurring in a critical site, for example (e.g.) intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, retroperitoneal, or * contributing to death. Clinically relevant non-major bleeding is defined as overt bleeding not meeting the criteria for major bleeding, but associated with: * medical intervention, or * unscheduled contact (visit or telephone call) with a physician, or * cessation (temporary) of study treatment, or * discomfort for the child such as pain or * impairment of activities of daily life (such as loss of school days or hospitalization).

  During or within 2 days after stop of study treatment (up to 32 days)

Secondary Outcomes (5)

• Number of Subjects With Symptomatic Recurrent Venous Thromboembolism

  From start of the study treatment up to 30-days post study treatment period (approximately 60 days)

• Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden on Repeat Imaging

  At the end of the 30-day treatment period

• Change From Baseline in Prothrombin Time at Specified Time Points

  Day 1 (2.5-4 hours post-dose); Day 15 (2-8 hours post-dose); Day 30 (10-16 hours post-dose)

• Change From Baseline in Activated Partial Thromboplastin Time at Specified Time Points

  Day 1 (2.5-4 hours post-dose); Day 15 (2-8 hours post-dose); Day 30 (10-16 hours post-dose)

• Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Specified Time Points

  Day 1 (30-90 minutes, 2.5-4 hours post-dose); Day 15 (2-8 hours post-dose) and Day 30 (10-16 hours post-dose)

Other Outcomes (1)

• Anti-factor Xa Values at Specified Time Points

  Day 1 (2.5-4 hours post-dose); Day 15 (2-8 hours post-dose) and Day 30 (10-16 hours post-dose)

Study Arms (1)

Rivaroxaban

EXPERIMENTAL

Age and body weight-adjusted twice daily dosing of rivaroxaban to achieve a similar exposure as that observed in adults treated for venous thromboembolism (VTE) with 20 mg rivaroxaban once daily

Drug: Rivaroxaban (Xarelto, BAY59-7939)

Interventions

Rivaroxaban (Xarelto, BAY59-7939) DRUG

With age and body-weight adjusted twice daily dosing of rivaroxaban as Oral Suspension to achieve a similar exposure as that observed in adults treated with 20 mg rivaroxaban once daily, and no other anticoagulant

Rivaroxaban

Eligibility Criteria

• Age: 6 Months - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children aged 6 months to \< 6 years who have been treated for at least 2 months or, in case of catheter related thrombosis, for at least 6 weeks with LMWH (low molecular weight heparin), fondaparinux and/or VKA (vitamin K antagonist) for documented symptomatic or asymptomatic venous thrombosis - Hemoglobin, platelets, creatinine, alanine aminotransferase (ALT) and bilirubin evaluated within 10 days prior to randomization
• Informed consent provided

You may not qualify if:

• Active bleeding or high risk for bleeding contraindicating anticoagulant therapy
• Symptomatic progression of venous thrombosis during preceding anticoagulant treatment
• Planned invasive procedures, including lumbar puncture and removal of non peripherally placed central lines during study treatment
• An estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m\^2
• 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 10\*9/L
• Hypertension defined as \> 95th age percentile
• Life expectancy \< 3 months
• Concomitant use of strong inhibitors of both cytochrome P450 isoenzyme 3A4 (CYP3A4) and P-glycoprotein (P-gp), i.e. all human immunodeficiency virus protease inhibitors and the following azole antimycotics agents: ketoconazole, itraconazole, voriconazole, posaconazole, if used systemically
• Concomitant use of strong inducers of CYP3A4, i.e. rifampicin, rifabutin, phenobarbital, phenytoin and carbamazepine
• Hypersensitivity or any other contraindication listed in the local labeling for the comparator treatment or experimental treatment
• Inability to cooperate with the study procedures
• Previous randomization to this study
• Participation in a study with an investigational drug or medical device within 30 days prior to randomization

Sponsors & Collaborators

• Bayer: lead
• Janssen Research & Development, LLC: collaborator

Study Sites (29)

Unknown Facility

Gainesville, Florida, 32610, United States

Location

Unknown Facility

Pensacola, Florida, 32504, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Unknown Facility

Chicago, Illinois, 60611, United States

Location

Unknown Facility

Indianapolis, Indiana, 46202, United States

Location

Unknown Facility

Parkville, Victoria, 3052, Australia

Location

Unknown Facility

Vienna, 1090, Austria

Location

Unknown Facility

São Paulo, São Paulo, 01227-200, Brazil

Location

Unknown Facility

São Paulo, Brazil

Location

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Toronto, Ontario, M5G 1X8, Canada

Location

Unknown Facility

Budapest, 1097, Hungary

Location

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Jerusalem, 9112001, Israel

Location

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Ramat Gan, 5262000, Israel

Location

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Milan, Lombardy, 20122, Italy

Location

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Turin, Piedmont, 10126, Italy

Location

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Padua, Veneto, 35128, Italy

Location

Unknown Facility

Setagaya City, Tokyo, 157-8535, Japan

Location

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Nijmegen, 6525 GA, Netherlands

Location

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Gdansk, 80-952, Poland

Location

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Olsztyn, 10-561, Poland

Location

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Moscow, 117997, Russia

Location

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Nizhny Novgorod, 603136, Russia

Location

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Saint Petersburg, 197022, Russia

Location

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Barcelona, 08035, Spain

Location

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Valencia, 46026, Spain

Location

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Bern, 3010, Switzerland

Location

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Newcastle upon Tyne, Tyne and Wear, NE1 4LP, United Kingdom

Location

Unknown Facility

Birmingham, West Midlands, B4 6NH, United Kingdom

Location

Unknown Facility

Cardiff, CF14 4XW, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 31420317 DERIVED

Related Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe.

MeSH Terms

Conditions

Venous Thromboembolism

Interventions

Rivaroxaban

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Study started as randomized but the Comparator arm sample size was too small for meaningful comparison; it was removed in Protocol amendment and approved by review board. Results only reported for rivaroxaban arm as single arm study.

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer

clinical-trials-contact@bayer.com

(+)1-888-84 22937

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2014
• First Posted: December 5, 2014
• Study Start: January 15, 2015
• Primary Completion: April 5, 2017
• Study Completion: April 5, 2017
• Last Updated: August 21, 2018
• Results First Posted: June 13, 2018

Record last verified: 2018-07

Locations

CA (1); HU (1); US (5); BR (2); AU (1); PL (2); NL (1); CH (1); GB (3); RU (3); JP (1); ES (2); IT (3); IL (2)