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

Bayer46 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Venous Thromboembolism

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

Eligibility

Sex: ALLMin age: 6 MonthsMax age: 5 Years

Medical Language ↔ Plain English

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

Locations (29)

Unnamed facility

Gainesville, Florida, United States

Unnamed facility

Outcomes

Primary Outcomes

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).

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

Secondary Outcomes

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.

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

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.

Data from ClinicalTrials.gov

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