Edoxaban for Prevention of Blood Vessels Being Blocked by Clots (Thrombotic Events) in Children at Risk Because of Cardiac Disease
- Registration Number
- NCT03395639
- Lead Sponsor
- Daiichi Sankyo
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 168
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard of Care (SOC) Standard of Care (SOC) One out of three participants will be randomized for treatment with the institution's SOC regimen Edoxaban Edoxaban Two out of three participants will be randomized for treatment with edoxaban solution or tablets
- Primary Outcome Measures
Name Time Method Number of Participants With Adjudicated Bleeding Events Within the Main Treatment Period 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 Adjudicated bleeding events included major and clinically-relevant non-major (CRNM) bleeding events per International Society on Thrombosis and Haemostasis (ISTH) definition occurring within the main treatment period. Based on modified ISTH recommendations, major bleeding is defined as a composite (ie, any) of the following: fatal bleeding; and/or symptomatic bleeding in a critical area or organ; and/or bleeding causing a decrease in hemoglobin level of \>2 g/dL, or leading to transfusion of the equivalent of ≥2 units of whole blood or red cells. A CRNM bleed is an acute or sub-acute clinically overt bleed that does not meet the criteria for a major bleed but prompts a clinical response, in that it leads to at least one of the following: a hospital admission for bleeding, or a physician guided medical or surgical treatment for bleeding, or a change in antithrombotic therapy. Minor bleeding is any other overt bleeding event that does not meet criteria for either major or CRNM bleeding.
- Secondary Outcome Measures
Name Time Method Number of Participants With Symptomatic Thromboembolic Events (TE) in the Systemic Arterial or Venous Pathways Within the Main Treatment Period 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 Symptomatic thromboembolic events (TE) in the systemic arterial or venous pathways include deep vein thrombosis (DVT), pulmonary embolism (PE), stroke, intracardiac thrombus, and myocardial infarction (MI).
Number of Participants Who Died as a Result of Thromboembolic Event Within the Main Treatment Period 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 Symptomatic thromboembolic events (TE) in the systemic arterial or venous pathways include deep vein thrombosis (DVT), pulmonary embolism (PE), stroke, intracardiac thrombus, and myocardial infarction (MI).
Number of Participants Who Died as a Result of Any Cause (All-Cause Mortality) Within the Main Treatment Period 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 Death due to any cause (all-cause mortality) was assessed.
Number of Participants With Adjudicated Bleeding Events During the Extension Period Month 4 up to Month 13 Adjudicated bleeding events included major and clinically-relevant non-major (CRNM) bleeding events per International Society on Thrombosis and Haemostasis (ISTH) definition occurring within the main treatment period. Based on modified ISTH recommendations, major bleeding is defined as a composite (ie, any) of the following: fatal bleeding; and/or symptomatic bleeding in a critical area or organ; and/or bleeding causing a decrease in hemoglobin level of \>2 g/dL, or leading to transfusion of the equivalent of ≥2 units of whole blood or red cells. A CRNM bleed is an acute or sub-acute clinically overt bleed that does not meet the criteria for a major bleed but prompts a clinical response, in that it leads to at least one of the following: a hospital admission for bleeding, or a physician guided medical or surgical treatment for bleeding, or a change in antithrombotic therapy. Minor bleeding is any other overt bleeding event that does not meet criteria for either major or CRNM bleeding.
Number of Participants With Symptomatic Thromboembolic Events (TE) in the Systemic Arterial or Venous Pathways During the Extension Period Month 4 up to Month 13 Symptomatic thromboembolic events (TE) in the systemic arterial or venous pathways include deep vein thrombosis (DVT), pulmonary embolism (PE), stroke, intracardiac thrombus, and myocardial infarction (MI).
Number of Participants Who Died as a Result of Thromboembolic Event During the Extension Period Month 4 up to Month 13 Symptomatic thromboembolic events (TE) in the systemic arterial or venous pathways include deep vein thrombosis (DVT), pulmonary embolism (PE), stroke, intracardiac thrombus, and myocardial infarction (MI).
Number of Participants Who Died as a Result of Any Cause (All-Cause Mortality) During the Extension Period Month 4 up to Month 13 Death due to any cause (all-cause mortality) was assessed.
Trial Locations
- Locations (48)
University Hospital Center Zagreb
🇭🇷Zagreb, Croatia
CHU Sainte-Justine
🇨🇦Montréal, Quebec, Canada
McMaster Children's Hospital
🇨🇦Hamilton, Ontario, Canada
Gottsegen Gyorgy Orszagos Kardiologiai Intezet
🇭🇺Budapest, Hungary
University of Florida College of Medicine
🇺🇸Gainesville, Florida, United States
Kepler Universitätsklinikum Med Campus IV
🇦🇹Linz, Austria
Pediatric and Congenital Cardiology and Pulmonology Department; Arnaud De Villeneuve University Hospital
🇫🇷Montpellier, Herault, France
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
🇭🇺Szeged, Hungary
Ain Shams University Hospital
🇪🇬Cairo, Egypt
Zagazig University Hospital
🇪🇬Zagazig, Al Sharkeya, Egypt
Hôpital Des Enfants, Bâtiment Modulaire
🇫🇷Toulouse cedex 9, Haute Garonne, France
McGill University Health Centre/Glen Site/Montreal Children's Hospital
🇨🇦Pierrefonds, Quebec, Canada
Erciyes University Medical Faculty, Department of Children Hospital
🇹🇷Edirne, Kayseri, Turkey
Alexandria Clinical Research Center, Faculty of Medicine
🇪🇬Alexandria, Egypt
Kasr Elainy School of Medicine, Abo Elreesh Hospital (Japanese Hospital), Ali Basha Ibrahim ST Faculty of Medicine Cairo University
🇪🇬Cairo, Egypt
Pediatric Cardiology Department, Hospital Necker Enfants Malades, APHP, Université Paris Descartes
🇫🇷Paris, Paris Cedex 15, France
Hotel Dieu de France Hospital
🇱🇧Beirut, Lebanon
Soroka University Medical Center
🇮🇱Be'er Sheva, Israel
Cardon Childrens Medical Center
🇺🇸Mesa, Arizona, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Seattle Children's Research Institute
🇺🇸Seattle, Washington, United States
University of California-San Francisco Department of Pediatrics - Hematology/Oncology
🇺🇸San Francisco, California, United States
OU Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
Cedars Sinai Medical Center (ECG)
🇺🇸Los Angeles, California, United States
Nirmal Hospital Private Limited
🇮🇳Sūrat, Gujarat, India
Hadassah University Hospital - Ein Kerem
🇮🇱Jerusalem, Israel
Sheba Medical Center
🇮🇱Ramat Gan, Israel
Institute of Child Health
🇮🇳Kolkata, India
Children's Heart Centre at the American University of Beirut Medical Center
🇱🇧Beirut, Lebanon
Hacettepe University Medical Faculty
🇹🇷Ankara, Turkey
Communal Institution Dnipropetrovsk Regional Pediatric Clinical Hospital of Dnipropetrovsk Regional Council, State Institution Dnipropetrovsk Medical Academy of MoH of Ukraine
🇺🇦Dnipro, Ukraine
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Ege University Faculty of Medicine Department of Child Health and Diseases
🇹🇷İzmir, Turkey
Izmir-Dr. Behçet Uz. Pediatric Diseases and Surgery Training and Research Hospital- Izmir Dr. Behcet Uz Cocuk Hastaliklari ve Cerrahisi Egitim ve Arastirma Hastanesi
🇹🇷İzmir, Turkey
Communal Healthcare Institution Regional Pediatric Clinical Hospital, Kharkiv National Medical University
🇺🇦Kharkiv, Ukraine
Glenfield Hospital
🇬🇧Leicester, Leicestershire, United Kingdom
Ward 2B, Royal Hospital for Children
🇬🇧Glasgow, Strathclyde, United Kingdom
Vynnitsa Regional Children Clinical Hospital Policlinic Dept
🇺🇦Vinnytsia, Ukraine
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Ochsner Medical Center
🇺🇸New Orleans, Louisiana, United States
Novant Health Heart and Vascular institute
🇺🇸Charlotte, North Carolina, United States
Wake Forest University Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
East Carolina Heart Institute @ ECU
🇺🇸Greenville, North Carolina, United States
Suez Canal University Hospital
🇪🇬Ismailia, Egypt
Istanbul University Istanbul Medical Faculty
🇹🇷Istanbul, Turkey
Royal Brompton Hospital
🇬🇧London, Greater London, United Kingdom