Health Condition 1: I749- Embolism and thrombosis of unspecified artery
Conditions
Interventions
Intervention1: Edoxaban Treatment arm
: For subjects 12 to 18 years old:
-60 mg dose will be dispensed as two 30 mg tablets
45 mg dose will be dispensed as one 30 mg and one 15 mg tablet or as 7.510 mL from an individual bottle of oral suspension 60 mg.
Subjects younger than 12 years of age will only receive edoxaban gran
Sponsors
Daiichi Sankyo
Daiichi Sankyo
Eligibility
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, Kawasaki disease, and Blalock- Taussig and Glenn surgery. 2. Male or female children between 1 and age in the edoxaban arm have been evaluated at the end of the 3-month treatment period. 3. Subject and/or parent(s)/legal guardian(s) or legally acceptable representative is informed and provides signed consent for the child to participate in the study with edoxaban treatment. Pediatric subjects with appropriate intellectual maturity will be required to sign an assent form in addition to the signed informed consent from the parent(s)/legal guardian(s) or any legally acceptable representative. 4. Female subjects of childbearing potential must test negative for pregnancy at Screening and must consent to avoid becoming pregnant by using a locally approved contraception method throughout the study.
Exclusion criteria
Exclusion criteria: Subjects with evidence of the following up to randomization: -Symptomatic venous or arterial TE -Asymptomatic venous or arterial TE found by routine imaging -Asymptomatic intracardiac thrombosis confirmed by a transthoracic echocardiogram during study screening period. Note: Valid echocardiograms are defined here as 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. Subjects with a contraindication to the use of heparin (UFH or LMWH) and/or VKA (see Appendix 17.4). 5. 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 (see Appendix 17.5). 6. Administration of rifampin is prohibited during the study and subjects on concomitant use of rifampin are excluded (see Appendix 17.5.6). 7. 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 Ã? the upper limit of normal (ULN) or total bilirubin (TBL) >2 Ã? ULN with direct bilirubin >20% of the total at Screening. 8. Subjects with estimated glomerular filtration rate (eGFR) 9. Subjects with stage 2 hypertension defined as blood pressure (BP) systolic and/or diastolic confirmed >99th percentile plus 5 mmHg (see Appendix 17.10). 10. Subjects with thrombocytopenia (thrombocytes 11. Subjects with Fontan procedure with a history of or signs/symptoms suggestive of protein-losing enteropathy. 12. Subjects with a life expectancy less than the expected study duration (3 months). 13. Subjects who are known to be pregnant or breastfeeding. 14. Subjects who are not using an approved method of contraception ( 15. 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 including contraindicated medications 16. Subject who participated in another clinical study or treated with an experimental therapy with less than a 30-day washout period prior to the Screening Visit.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective is to compare the safety of edoxaban with the standard of care (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] definition1 occurring in the Main Treatment PeriodTimepoint: from the date of first dose of study drug to Month 3 Visit, or to the date of last dose of study drug if study treatment is discontinued | — |
Secondary
| Measure | Time frame |
|---|---|
| -To assess the efficacy of edoxaban with regard to all-cause mortality occurring during the Extension Period Timepoint: during the Extension Period;-To assess the efficacy of edoxaban with regard to death as a result of a TE occurring during the Extension Period.Timepoint: during the Extension Period.;-To assess the efficacy of edoxaban with regard to the development of symptomatic TE, and asymptomatic intracardiac thrombus identified by cardiac imaging occurring during the Extension Period.Timepoint: during the Extension Period.;-To assess the safety of edoxaban with regard to all bleedings occurring during the Extension Period. Timepoint: during the Extension Period.;-To assess the safety of edoxaban with regard to the combination of major and CRNM bleedings occurring during the Extension Period (from Month 3 Visit to last dose plus 30 days).Timepoint: from Month 3 Visit to last dose plus 30 days;-To compare edoxaban against SOC with regard to all-cause mortality from randomization to Month 3 VisitTimepoint: from randomization to Month 3 Visit;-To compare the efficacy of edoxaban against SOC with regard to death as a result of a TE occurring from randomization to Month 3 VisitTimepoint: from randomization to Month 3 Visit;-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, systemic embolic event (SEE), myocardial infarction (MI), and asymptomatic intracardiac thrombus identified by cardiac imaging occurring from randomization to Month 3 VisitTimepoint: from randomization to Month 3 Visit;-To compare the safety of edoxaban against SOC with regard to all bleedings that occur in the Main Treatment Period: from the date of first dose of study drug to Month 3 Visit, or to the date of last dose of study drug if study treatment is discontinuedTimepoint: from the da | — |
Countries
Austria, Canada, Croatia, Egypt, France, Germany, Hungary, India, Israel, Italy, Lebanon, Poland, Russian Federation, Spain, Turkey, Ukraine, United Kingdom, United States of America
Contacts
Public ContactSuneela Thatte
IQVIA RDS (India) Private Limited
Outcome results
None listed