Edoxaban for Prevention of Blood Vessels Being Blocked by Clots (Thrombotic Events) in Children at Risk Because of Cardiac Disease

Daiichi Sankyo

Status and phase

Completed

Phase 3

Conditions

Cardiac Disease

Treatments

Drug: Standard of Care (SOC)

Drug: Edoxaban

Study type

Interventional

Funder types

Industry

Identifiers

NCT03395639

2017-000475-90 (EudraCT Number)

DU176b-C-U313

Details and patient eligibility

About

A committee will judge the safety and effectiveness of edoxaban and the regular treatment (standard of care).

All children in the study will receive free treatment. They will have a 2 in 3 chance to receive edoxaban, and a 1 in 3 chance to receive the standard of care for preventing blood clots.

The study will find out if edoxaban is safer and more effective than the standard of care.

Full description

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) bleeding per International Society on Thrombosis and Haemostasis [ISTH] definition.

The key secondary objective is 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.

Enrollment

168 patients

Sex

All

Ages

1 day to 17 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Is a child with cardiac disease who is at risk for thromboembolic complications and requires at least 3 months antithrombotic anticoagulant prophylaxis

Either one of the following:

a child with cardiac disease who has a history of cardiac shunt occlusion/thrombosis, with shunt still in place (secondary prevention).

OR
a child with cardiac disease who requires (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. Some examples of cardiac conditions at risk of thrombosis are Fontan surgery, heart failure, Kawasaki disease, and Blalock-Taussig and Glenn surgery.

Is a male or female child between 1 and <18 years of age (children between 38 weeks gestational age and 1 year of age will be included in the study, however, only after the safety and efficacy data of 50 subjects between 1 and <18 years of age in the edoxaban arm have been evaluated at the end of the 3-month treatment period)
Has parent(s)/legal guardian(s) or legally acceptable representative who is informed and provides signed consent for the child, to participate in the study with edoxaban treatment. Pediatric participants 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.
If a female subject of childbearing potential, tests negative for pregnancy at Screening and consents to avoid becoming pregnant by using a locally approved contraception method throughout the study

Exclusion criteria

Has evidence of symptomatic venous or arterial thrombosis and/or asymptomatic intracardiac thrombosis confirmed by a transthoracic echocardiogram during study screening period
Has mechanical heart valve(s)
Has active bleeding or high risk of bleeding contraindicating treatment with anticoagulant
Takes antithrombotic therapy (other than low-dose aspirin) that is not protocol-related
Administration of rifampin is prohibited during the study and subjects on concomitant use of rifampin are excluded
Has any hepatic disease associated with coagulopathy leading to a clinically relevant bleeding risk
Has estimated glomerular filtration rate (eGFR) <30% of normal for age and size
Has stage 2 hypertension defined as blood pressure systolic and/or diastolic confirmed >99th percentile plus 5 mmHg
Has thrombocytopenia or life expectancy less than three months
Has had Fontan procedure with a history of or signs/symptoms suggestive of protein-losing enteropathy
Is pregnant or breastfeeding
Has a contraindication to the use of heparin and/or vitamin K antagonist (VKA)
Has any condition that, as judged by the Investigator, would place the participant at increased risk of harm if he/she participated in the study, including contraindicated medications identified in the protocol