thromboembolism MedDRA version: 20.0 Level: LLT Classification code 10043566 Term: Thromboembolism System Organ Class: 100000004866
Conditions
Interventions
Trade Name: Lixiana 15 mg film-coated tablets
Product Code: DU176B
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: EDOXABAN (as anhydrous free form
CAS Number: 480449-71-6
Other descripti
Sponsors
Daiichi Sankyo Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must satisfy all of the following criteria to be eligible for the study: 1.Children with cardiac diseases who are at risk for thromboembolic complications and require at least 3 months antithrombotic anticoagulant prophylaxis. Either one of the following: a.Children with cardiac disease who have a history of cardiac shunt occlusion/thrombosis, with shunt still in place (secondary prevention). OR b.Children with cardiac disease who require (including those already taking, and those not yet taking) anticoagulation for primary prevention of TE. Cardiac conditions known to significantly increase the risk of thrombosis (hence, indications for primary TE prevention) are defined in Antithrombotic Therapy and Prevention of Thrombosis.1 Some examples of cardiac conditions at risk of thrombosis are Fontan surgery, heart failure, and Kawasaki disease, and Blalock-Taussig and Glenn surgery. 2.Male or female children between 1 and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following criteria will be disqualified from entering the study: 1.Subjects with evidence of symptomatic venous or arterial thrombosis and/or asymptomatic intracardiac thrombosis confirmed by a transthoracic echocardiogram during study screening period.Note: Valid echocardiograms are images taken within 5 weeks prior to Randomization Visit. 2.Subjects with mechanical heart valves. 3.Subjects with active bleeding or high risk of bleeding contraindicating treatment with anticoagulant. 4.Co-administration of antithrombotic therapy is contraindicated in edoxaban arm and SOC arm except for low dose aspirin defined as 1 to 5 mg/kg/day with maximum of 100 mg/day. 5.Subjects with hepatic disease associated with coagulopathy leading to a clinically relevant bleeding risk (aPTT >50 seconds or international normalized ratio [INR] >2.0 not related to anticoagulation therapy) or ALT >5 × the upper limit of normal (ULN) or total bilirubin (TBL) >2 × ULN with direct bilirubin >20% of the total at Screening. 6.Subjects with estimated glomerular filtration rate (eGFR) 99th percentile plus 5 mmHg. 8.Subjects with thrombocytopenia (thrombocytes <50 × 109/L). 9.Subjects with Fontan procedure with a history of or signs/symptoms suggestive of protein-losing enteropathy. 10.Subjects with a life expectancy less than the expected study duration (3 months). 11.Subjects who are known to be pregnant or breastfeeding. 12.Subjects with any condition that, as judged by the Investigator, would place the subject at increased risk of harm if he/she participated in the study. 13.Subjects with a contraindication to the use of heparin and/or VKA (UFH or LMWH) and/or VKA
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare the safety of edoxaban with the SOC in pediatric subjects with cardiac diseases at risk of thromboembolic complications who need primary or secondary anticoagulant prophylaxis with regard to the combination of major and clinically relevant non-major (CRNM) bleedings per International Society on Thrombosis and Haemostasis [ISTH] definition occurring on treatment (ie, during treatment or within 3 days of completing, interrupting or stopping study treatment during the first 3-month treatment period).;Secondary Objective: -To compare the efficacy of edoxaban against SOC with regard to the development of symptomatic thromboembolic events (TE) in the systemic arterial or venous pathways including deep vein thrombosis (DVT), pulmonary embolism (PE), stroke, intracardiac thrombus and myocardial infarction (MI), and asymptomatic intracardiac thrombus identified by cardiac imaging during the first 3-month treatment period plus 3 days and occurring from randomization to the last dose plus 30 days. -To compare the efficacy of edoxaban against SOC with regard to death as a result of a TE occurring from randomization to the last dose plus 30 days. -To compare edoxaban against SOC with regard to the composite combination of major and CRNM bleedings from first to the last dose plus 30 days. -To compare the safety of edoxaban against SOC with regard to all bleedings which occur from first to the last dose plus 30 days. Please refer to remaining text on page 4 of the protocol Version 1.0 dated 27 June 2017.;Primary end point(s): The primary safety endpoint is a combination of major bleeding events and CRNM bleeding events per ISTH definition occurring on treatment (ie, during treatment or within 3 days of completing or interrupting or stopping study treatment during the first 3-month treatment period).;Timepoint(s) of evaluation of this end point: 3 month treatment period. Analysis of Primary Safety Endpoint: -A descriptive statist | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary safety endpoints are: -A combination of major and CRNM bleedings from first to the last dose plus 30 days. -All bleeding events from first dose to the last dose plus 30 days. -All bleeding events occurring on-treatment (during treatment or within 3 days of completing or interrupting or stopping study treatment during the first 3-month treatment period). The secondary efficacy endpoints are: -The combination of symptomatic TE in the systemic arterial or venous pathways including DVT, PE, stroke, intracardiac thrombus and MI, and asymptomatic intracardiac thrombus identified by cardiac imaging, which occur from randomization to 3 months of treatment plus 3 days. -The combination of symptomatic TE in the systemic arterial or venous pathways including DVT, PE, stroke, intracardiac thrombus and MI, and asymptomatic intracardiac thrombus identified by cardiac imaging, which occur from randomization to the date of the last dose of study drug plus 30 days. -Deaths as a result of TE which occurs from randomization to the date of the last dose of study drug plus 30 days. -All-cause mortality from randomization to last dose plus 30 days. Pharmacokinetic (PK)/Pharmacodynamic (PD)/Biomarker Endpoint(s) -Plasma concentrations of edoxaban and its metabolite, D21-2393, will be assessed in subjects who receive at least 1 dose of edoxaban treatment and have measurable concentrations of edoxaban and/or D21-2393. Population PK analysis will be conducted to characterize the PK profiles of edoxaban in this target subject population. -The PD biomarkers of coagulation, PT, aPTT, and anti-activated Factor X (FXa) will be assessed as secondary endpoints in edoxaban-treated subjects. -Other biomarkers may be tested related to coagulation and/or edoxaban’s mechanism of action.;Timepoint(s) of evaluation of this end point: Analysis of Secondary Safety and Efficacy Endpoints: -The incidence, annualized event rate, and rate difference between edoxa | — |
Countries
Austria, Canada, Croatia, Egypt, France, Germany, Hungary, India, Israel, Italy, Lebanon, Poland, Russian Federation, Spain, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Contact
Daiichi Sankyo Inc
Outcome results
None listed