An Open-Label, Study to Evaluate safety and efficacy of Edoxaban tosylate in children with heart disease at risk of a blood clot.

Phase 1

• Conditions: thromboembolism; MedDRA version: 20.0Level: LLTClassification code 10043566Term: ThromboembolismSystem Organ Class: 100000004866; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2017-000475-90-AT
• Lead Sponsor: Daiichi Sankyo Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-02-05
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 150

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 criteria may apply:
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 <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.

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 Randomization and must consent to avoid becoming pregnant by using a locally approved contraception method throughout the study. For locally approved contraceptive methods.

5.If the subject has a history of thromboembolic Event (TE) that meets all of the following criteria:
-old,organized and /or resolved per the discretion of the Principal Investigator (confirmed of an old, organized and or resolved TE is not required by any imaging studies and
-The subject is asymptomatic and
- The subject continues to require at least 3 months of anti -coagulation treatment , and
-There is no intracardiac thrombus or thrombi on the screening echo , and
-all other inclusion and exclusion criteria are met.
Are the trial subjects under 18? yes
Number of subjects for this age range: 150
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects who meet any of the following criteria will be disqualified from entering the study:

1.Subjects with a history 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 an 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.
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.
6.Administration of rifampin is prohibited during the study and subjects
on concomitant use of rifampin are excluded.
7a.Subjects with severe hepatic impairment or hepatic disease associated with coagulopathy ( e.g. acute hepatitis, chronic active hepatitis, and cirrhosis)
b) subjects with ALT >5 × the upper limit of normal (ULN) or total bilirubin (TBL) >2 × ULN with direct bilirubin >20% of the total at Screening.
c) Subjects with aPTT>50 seconds or international normalised ratio [INR] >2.0 nor related to anticoagulation therapy at screening.
8.Subjects with estimated glomerular filtration rate (eGFR) <30% of
normal for age and size.
9.Subjects with stage 2 hypertension defined as blood pressure (BP)
systolic and/or diastolic confirmed >99th percentile plus 5 mmHg.
10.Subjects with thrombocytopenia (thrombocytes <50 × 109/L).
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 identified.
16.Subject who participated in another interventional clinical study or treated with an
experimental therapy with less than a 30-day washout period prior to
the Screening Visit.
17. If any imaging is performed prior to randomization and results show a newly detected unorganized thrombus, these subjects are NOT eligible for the study.
18. Hypersensitivity to the active ingredient or to any of the excipients of any components of the trial treatment.
19.Patients with a history of thrombosis who are diagnosed with anti-phospholipid syndrome who are triple positive (for lupus anticoagulant, anti cardiolipin antibodies , and anti- beta 2-glycoprotein I antibodies.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified