Clinical trial NCT03395639: Edoxaban for Prevention of Blood Vessels Being Blocked by Clots (Thrombotic Events) in Children at Risk Because of Cardiac Disease
Official title: An Open-label, Randomised, Parallel-group, Multicentre, Observational Trial to Evaluate Safety and Efficacy of Edoxaban Tosylate in Children From 38 Weeks Gestational Age to Less Than 18 Years of Age With Cardiac Diseases at Risk of Thromboembolic Events
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cardiac Disease
Keywords: Children
Pediatrics
Cardiac disease with potential for thromboembolic complications
Prophylactic treatment
Anticoagulant drugs
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2018-01-10
Enrollment: 168
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

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

Primary outcomes:
measure: Number of Participants With Adjudicated Bleeding Events Within the Main Treatment Period
timeFrame: Date of first dose of study drug up to the Month 4 or to the date of last dose of study drug if study treatment was discontinued, whichever was earlier
Secondary outcomes:
measure: Number of Participants With Symptomatic Thromboembolic Events (TE) in the Systemic Arterial or Venous Pathways Within the Main Treatment Period
timeFrame: Date of first dose of study drug up to the Month 4 or to the date of last dose of study drug if study treatment was discontinued, whichever was earlier
measure: Number of Participants Who Died as a Result of Thromboembolic Event Within the Main Treatment Period
timeFrame: Date of first dose of study drug up to the Month 4 or to the date of last dose of study drug if study treatment was discontinued, whichever was earlier
measure: Number of Participants Who Died as a Result of Any Cause (All-Cause Mortality) Within the Main Treatment Period
timeFrame: Date of first dose of study drug up to the Month 4 or to the date of last dose of study drug if study treatment was discontinued, whichever was earlier
measure: Number of Participants With Adjudicated Bleeding Events During the Extension Period
timeFrame: Month 4 up to Month 13
measure: Number of Participants With Symptomatic Thromboembolic Events (TE) in the Systemic Arterial or Venous Pathways During the Extension Period
timeFrame: Month 4 up to Month 13
measure: Number of Participants Who Died as a Result of Thromboembolic Event During the Extension Period
timeFrame: Month 4 up to Month 13
measure: Number of Participants Who Died as a Result of Any Cause (All-Cause Mortality) During the Extension Period
timeFrame: Month 4 up to Month 13
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Mesa
country: United States
facility: Cardon Childrens Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center (ECG)
state: California
city: San Francisco
country: United States
facility: University of California-San Francisco Department of Pediatrics - Hematology/Oncology
state: California
city: Gainesville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Charlotte
country: United States
facility: Novant Health Heart and Vascular institute
state: North Carolina
city: Greenville
country: United States
facility: East Carolina Heart Institute @ ECU
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center
state: North Carolina
city: Oklahoma City
country: United States
facility: OU Health Sciences Center
state: Oklahoma
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Research Institute
state: Washington
city: Linz
country: Austria
facility: Kepler Universitätsklinikum Med Campus IV
city: Hamilton
country: Canada
facility: McMaster Children's Hospital
state: Ontario
city: Montréal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
city: Pierrefonds
country: Canada
facility: McGill University Health Centre/Glen Site/Montreal Children's Hospital
state: Quebec
city: Zagreb
country: Croatia
facility: University Hospital Center Zagreb
city: Zagazig
country: Egypt
facility: Zagazig University Hospital
state: Al Sharkeya
city: Alexandria
country: Egypt
facility: Alexandria Clinical Research Center, Faculty of Medicine
city: Cairo
country: Egypt
facility: Kasr Elainy School of Medicine, Abo Elreesh Hospital (Japanese Hospital), Ali Basha Ibrahim ST Faculty of Medicine Cairo University
city: Cairo
country: Egypt
facility: Ain Shams University Hospital
city: Ismailia
country: Egypt
facility: Suez Canal University Hospital
city: Toulouse cedex 9
country: France
facility: Hôpital Des Enfants, Bâtiment Modulaire
state: Haute Garonne
city: Montpellier
country: France
facility: Pediatric and Congenital Cardiology and Pulmonology Department; Arnaud De Villeneuve University Hospital
state: Herault
city: Paris
country: France
facility: Pediatric Cardiology Department, Hospital Necker Enfants Malades, APHP, Université Paris Descartes
state: Paris Cedex 15
city: Budapest
country: Hungary
facility: Gottsegen Gyorgy Orszagos Kardiologiai Intezet
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
city: Sūrat
country: India
facility: Nirmal Hospital Private Limited
state: Gujarat
city: Kolkata
country: India
facility: Institute of Child Health
city: Be'er Sheva
country: Israel
facility: Soroka University Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital - Ein Kerem
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Beirut
country: Lebanon
facility: Children's Heart Centre at the American University of Beirut Medical Center
city: Beirut
country: Lebanon
facility: Hotel Dieu de France Hospital
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Edirne
country: Turkey
facility: Erciyes University Medical Faculty, Department of Children Hospital
state: Kayseri
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: Istanbul
country: Turkey
facility: Istanbul University Istanbul Medical Faculty
city: İzmir
country: Turkey
facility: Ege University Faculty of Medicine Department of Child Health and Diseases
city: İzmir
country: Turkey
facility: Izmir-Dr. Behçet Uz. Pediatric Diseases and Surgery Training and Research Hospital- Izmir Dr. Behcet Uz Cocuk Hastaliklari ve Cerrahisi Egitim ve Arastirma Hastanesi
city: Dnipro
country: Ukraine
facility: Communal Institution Dnipropetrovsk Regional Pediatric Clinical Hospital of Dnipropetrovsk Regional Council, State Institution Dnipropetrovsk Medical Academy of MoH of Ukraine
city: Kharkiv
country: Ukraine
facility: Communal Healthcare Institution Regional Pediatric Clinical Hospital, Kharkiv National Medical University
city: Vinnytsia
country: Ukraine
facility: Vynnitsa Regional Children Clinical Hospital Policlinic Dept
city: London
country: United Kingdom
facility: Royal Brompton Hospital
state: Greater London
city: Leicester
country: United Kingdom
facility: Glenfield Hospital
state: Leicestershire
city: Glasgow
country: United Kingdom
facility: Ward 2B, Royal Hospital for Children
state: Strathclyde
Study officials:
affiliation: Daiichi Sankyo
name: Clinical Study Leader
role: STUDY_DIRECTOR
References: