Edoxaban for Prevention of Blood Vessels Being Blocked by Clots (Thrombotic Events) in Children at Risk Because of Cardiac Disease
Condition: Cardiac Disease
MeSH terms: Heart Diseases
Intervention: Edoxaban; Standard of Care (SOC)
Intervention description: Edoxaban 15 mg or 30 mg tablets for participants 12 to <18 years of age, or 60 mg edoxaban suspension (dosed as mg/kg) for participants under 12 years of age (and optionally, 12 or older), for oral administration; Standard of care could include low molecular weight heparin (LMWH) and/or VKA according to the clinical site's SOC treatment regimen
Intervention MeSH terms: Heparin; Enoxaparin; Warfarin; Edoxaban
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 168.0
Sex: All
Minimum age: 1 Day
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Children; Pediatrics; Cardiac disease with potential for thromboembolic complications; Prophylactic treatment; Anticoagulant drugs

Summary:

      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.
    

Eligibility criteria:

        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:

          1. a child with cardiac disease who has a history of cardiac shunt occlusion/thrombosis,
             with shunt still in place (secondary prevention).

             OR

          2. 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