Venous ThromboembolismPhase 2EINSTEINJrNCT02309411
EINSTEIN Junior Phase II: Oral Rivaroxaban in Young Children With Venous Thrombosis
A Phase 2 study testing Rivaroxaban (Xarelto, BAY59-7939) in people with Venous Thromboembolism, run by Bayer at 29 sites in 15 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 months to 5 years
- Conditions the study is for
- Venous Thromboembolism
- What is being tested?
- Rivaroxaban (Xarelto, BAY59-7939)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 29 sitesin 15 countries
- Study dates
- 15 Jan 2015to 5 Apr 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
29 sites in 15 countries.
29 sites in 15 countries
United States5 sites
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
Study site
Chicago, Illinois, 60611
Study site
Gainesville, Florida, 32610
Study site
Indianapolis, Indiana, 46202
Study site
Pensacola, Florida, 32504
Italy3 sites
Study site
Milan, Lombardy, 20122
Study site
Padova, Veneto, 35128
Study site
Turin, Piedmont, 10126
Russia3 sites
Study site
Moscow, 117997
Study site
Nizhny Novgorod, 603136
Study site
Saint Petersburg, 197022
United Kingdom3 sites
Study site
Birmingham, West Midlands, B4 6NH
Study site
Cardiff, CF14 4XW
Study site
Newcastle upon Tyne, Tyne and Wear, NE1 4LP
About this study
Official title: 30-day, Single-arm Study of the Safety, Efficacy and the Pharmacokinetic and Pharmacodynamic Properties of Oral Rivaroxaban in Young Children With Various Manifestations of Venous Thrombosis
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
- Being tested
- Rivaroxaban (Xarelto, BAY59-7939)
- Keywords
- Pediatric
- Medical subject headings
- Venous Thromboembolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Rivaroxaban (Xarelto, BAY59-7939) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
Venous thromboembolism is the formation of a blood clot (thrombus) inside a blood vessel, obstructing the flow of blood through the circulatory system. The occurrence of recurrent venous thromboembolism was summarized by age group. Symptomatic recurrence, which is the composite of deep Vein Thrombosis (DVT), non-fatal Pulmonary Embolism (PE), and fatal PE of venous thrombosis, had to be documented using appropriate (repeat) imaging test.
Measured: 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
The occurrence of asymptomatic deterioration in thrombotic burden was summarized by age group. At the end of the 30-day treatment period, a repeat imaging of the thrombus was performed. The images of the index event and repeat imaging were adjudicated by the central independent adjudication committee (CIAC). The thrombotic burden at the time of the index event was compared to the thrombotic burden at the time of repeat imaging. The outcome of the adjudication was classified as normalized, improved, no relevant change, deteriorated, or not evaluable. Due to missing repeated imaging, thrombotic burden assessments were not done in some subjects.
Measured: At the end of the 30-day treatment period
Change From Baseline in Prothrombin Time at Specified Time Points
Prothrombin time is a global clotting test used for the assessment of the extrinsic pathway of the blood coagulation cascade. Day 30 (10-16 hours post-dose) was considered as a baseline.
Measured: 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
The Activated partial thromboplastin time (aPTT) is a screening test for the intrinsic pathway. Day 30 (10-16 hours post-dose) was considered as a baseline.
Measured: 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
Concentration of rivaroxaban in plasma was measured at Day 1, 15 and 30 at specified time points. In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2014 (estimated)
- Study start15 Jan 2015
- Primary completion5 Apr 2017
- Study completion5 Apr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Venous ThromboembolismStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Janssen Research & Development, LLC
- Responsible party
- Sponsor
- Investigators
- Bayer Study Director, Study director, Bayer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02309411
- Sponsor's protocol ID
- 14374
- Other IDs
- 2014-000566-22, 2014
- Acronym
- EINSTEINJr
- Status last verified
- Jul 2018
- First submitted
- 24 Nov 2014
- Last updated
- 21 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 31420317
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 30-day, Single-arm Study of the Safety, Efficacy and the Pharmacokinetic and Pharmacodynamic Properties of Oral Rivaroxaban in Young Children With Various Manifestations of Venous Thrombosis
- ClinicalTrials.gov ID
- NCT02309411
- Acronym / sponsor ID
- EINSTEINJr / 14374
- Conditions
- Venous Thromboembolism
- Keywords
- Pediatric
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Collaborators
- Janssen Research & Development, LLC
- Study start
- 15 Jan 2015 (actual)
- Primary completion
- 5 Apr 2017 (actual)
- Study completion
- 5 Apr 2017 (actual)
- First posted
- 5 Dec 2014 (estimated)
- Results
- Posted 13 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rivaroxaban | Experimental | Drug: Rivaroxaban (Xarelto, BAY59-7939)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 |
Who may qualify
- Ages
- 6 months to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rivaroxaban (Xarelto, BAY59-7939)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 | Drug | Rivaroxaban |
Primary outcome
Number of Subjects With Major Bleeding and Clinically Relevant Non-Major Bleeding Events
Time frame: During or within 2 days after stop of study treatment (up to 32 days)
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).
5 secondary outcomes
Number of Subjects With Symptomatic Recurrent Venous Thromboembolism
Time frame: 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
Time frame: At the end of the 30-day treatment period
Change From Baseline in Prothrombin Time at Specified Time Points
Time frame: 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
Time frame: 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
Time frame: 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31420317Monagle 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.
- Click here to find information about studies related to Bayer Healthcare products conducted in Europe.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bayer Study Director study director
Bayer
29 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rivaroxaban (Xarelto, BAY59-7939) in people with Venous Thromboembolism, run by Bayer at 29 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, Italy, Russia, United Kingdom, Brazil and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects With Major Bleeding and Clinically Relevant Non-Major Bleeding Events (time frame: During or within 2 days after stop of study treatment (up to 32 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02309411, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2018.