Clinical trial NCT02309411: EINSTEIN Junior Phase II: Oral Rivaroxaban in Young Children With Venous Thrombosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Venous Thromboembolism
Keywords: Pediatric
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Janssen Research & Development, LLC
First posted: 2014-12-05
Enrollment: 46
Sex: ALL
Minimum age (years): 6
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of Subjects With Major Bleeding and Clinically Relevant Non-Major Bleeding Events
timeFrame: During or within 2 days after stop of study treatment (up to 32 days)
Secondary outcomes:
measure: Number of Subjects With Symptomatic Recurrent Venous Thromboembolism
timeFrame: From start of the study treatment up to 30-days post study treatment period (approximately 60 days)
measure: Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden on Repeat Imaging
timeFrame: At the end of the 30-day treatment period
measure: Change From Baseline in Prothrombin Time at Specified Time Points
timeFrame: Day 1 (2.5-4 hours post-dose); Day 15 (2-8 hours post-dose); Day 30 (10-16 hours post-dose)
measure: Change From Baseline in Activated Partial Thromboplastin Time at Specified Time Points
timeFrame: Day 1 (2.5-4 hours post-dose); Day 15 (2-8 hours post-dose); Day 30 (10-16 hours post-dose)
measure: Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Specified Time Points
timeFrame: 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:
measure: Anti-factor Xa Values at Specified Time Points
timeFrame: Day 1 (2.5-4 hours post-dose); Day 15 (2-8 hours post-dose) and Day 30 (10-16 hours post-dose)
Locations:
city: Gainesville
country: United States
state: Florida
city: Pensacola
country: United States
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Parkville
country: Australia
state: Victoria
city: Wien
country: Austria
city: São Paulo
country: Brazil
state: Sao Paulo
city: São Paulo
country: Brazil
city: Toronto
country: Canada
state: Ontario
city: Budapest
country: Hungary
city: Jerusalem
country: Israel
city: Ramat Gan
country: Israel
city: Milano
country: Italy
state: Lombardia
city: Torino
country: Italy
state: Piemonte
city: Padova
country: Italy
state: Veneto
city: Setagaya
country: Japan
state: Tokyo
city: Nijmegen
country: Netherlands
city: Gdansk
country: Poland
city: Olsztyn
country: Poland
city: Moscow
country: Russian Federation
city: Nizhny Novgorod
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Barcelona
country: Spain
city: Valencia
country: Spain
city: Bern
country: Switzerland
city: Newcastle Upon Tyne
country: United Kingdom
state: Tyne And Wear
city: Birmingham
country: United Kingdom
state: West Midlands
city: Cardiff
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: 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.