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

NCT ID: NCT03395639

Last Updated: 2022-07-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 168 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-15
• Study Completion Date: 2021-12-03

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.

Conditions

Cardiac Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Edoxaban

Two out of three participants will be randomized for treatment with edoxaban solution or tablets

Group Type: EXPERIMENTAL

Edoxaban

Intervention Type: DRUG

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 (SOC)

One out of three participants will be randomized for treatment with the institution's SOC regimen

Group Type: ACTIVE_COMPARATOR

Standard of Care (SOC)

Intervention Type: DRUG

Standard of care could include low molecular weight heparin (LMWH) and/or VKA according to the clinical site's SOC treatment regimen

Interventions

Edoxaban

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

Intervention Type: DRUG

Standard of Care (SOC)

Standard of care could include low molecular weight heparin (LMWH) and/or VKA according to the clinical site's SOC treatment regimen

Intervention Type: DRUG

Other Intervention Names

Lixiana; Savaysa; Warfarin/heparin; Enoxaparin

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

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Study Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Cardon Childrens Medical Center

Mesa, Arizona, United States

Cedars Sinai Medical Center (ECG)

Los Angeles, California, United States

University of California-San Francisco Department of Pediatrics - Hematology/Oncology

San Francisco, California, United States

University of Florida College of Medicine

Gainesville, Florida, United States

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

Ochsner Medical Center

New Orleans, Louisiana, United States

Novant Health Heart and Vascular institute

Charlotte, North Carolina, United States

East Carolina Heart Institute @ ECU

Greenville, North Carolina, United States

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, United States

OU Health Sciences Center

Oklahoma City, Oklahoma, United States

University of Virginia Health System

Charlottesville, Virginia, United States

Seattle Children's Research Institute

Seattle, Washington, United States

Kepler Universitätsklinikum Med Campus IV

Linz, , Austria

McMaster Children's Hospital

Hamilton, Ontario, Canada

CHU Sainte-Justine

Montreal, Quebec, Canada

McGill University Health Centre/Glen Site/Montreal Children's Hospital

Pierrefonds, Quebec, Canada

University Hospital Center Zagreb

Zagreb, , Croatia

Zagazig University Hospital

Zagazig, Al Sharkeya, Egypt

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

Ain Shams University Hospital

Cairo, , Egypt

Suez Canal University Hospital

Ismailia, , Egypt

Hôpital Des Enfants, Bâtiment Modulaire

Toulouse, Haute Garonne, France

Pediatric and Congenital Cardiology and Pulmonology Department; Arnaud De Villeneuve University Hospital

Montpellier, Herault, France

Pediatric Cardiology Department, Hospital Necker Enfants Malades, APHP, Université Paris Descartes

Paris, Paris Cedex 15, France

Gottsegen Gyorgy Orszagos Kardiologiai Intezet

Budapest, , Hungary

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont

Szeged, , Hungary

Nirmal Hospital Private Limited

Surat, Gujarat, India

Institute of Child Health

Kolkata, , India

Soroka University Medical Center

Beersheba, , Israel

Hadassah University Hospital - Ein Kerem

Jerusalem, , Israel

Sheba Medical Center

Ramat Gan, , Israel

Children's Heart Centre at the American University of Beirut Medical Center

Beirut, , Lebanon

Hotel Dieu de France Hospital

Beirut, , Lebanon

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Erciyes University Medical Faculty, Department of Children Hospital

Edirne, Kayseri, Turkey (Türkiye)

Hacettepe University Medical Faculty

Ankara, , Turkey (Türkiye)

Istanbul University Istanbul Medical Faculty

Istanbul, , Turkey (Türkiye)

Ege University Faculty of Medicine Department of Child Health and Diseases

Izmir, , Turkey (Türkiye)

Izmir-Dr. Behçet Uz. Pediatric Diseases and Surgery Training and Research Hospital- Izmir Dr. Behcet Uz Cocuk Hastaliklari ve Cerrahisi Egitim ve Arastirma Hastanesi

Izmir, , Turkey (Türkiye)

Communal Institution Dnipropetrovsk Regional Pediatric Clinical Hospital of Dnipropetrovsk Regional Council, State Institution Dnipropetrovsk Medical Academy of MoH of Ukraine

Dnipro, , Ukraine

Communal Healthcare Institution Regional Pediatric Clinical Hospital, Kharkiv National Medical University

Kharkiv, , Ukraine

Vynnitsa Regional Children Clinical Hospital Policlinic Dept

Vinnytsia, , Ukraine

Royal Brompton Hospital

London, Greater London, United Kingdom

Glenfield Hospital

Leicester, Leicestershire, United Kingdom

Ward 2B, Royal Hospital for Children

Glasgow, Strathclyde, United Kingdom

Countries

United States; Austria; Canada; Croatia; Egypt; France; Hungary; India; Israel; Lebanon; Spain; Turkey (Türkiye); Ukraine; United Kingdom

References

Portman MA, Jacobs JP, Newburger JW, Berger F, Grosso MA, Duggal A, Tao B, Goldenberg NA; ENNOBLE-ATE Trial Investigators. Edoxaban for Thromboembolism Prevention in Pediatric Patients With Cardiac Disease. J Am Coll Cardiol. 2022 Dec 13;80(24):2301-2310. doi: 10.1016/j.jacc.2022.09.031. Epub 2022 Oct 31.

Reference Type: DERIVED

PMID: 36328157 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2017-000475-90

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DU176b-C-U313

Identifier Type: -

Identifier Source: org_study_id