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Edoxaban for Thromboembolism Prevention in Pediatric Patients With Cardiac Disease
Michael A Portman1, Jeffrey P Jacobs2, Jane W Newburger3
1Seattle Children's Research Institute, and Division of Cardiology, Department of Pediatrics, University of Washington, Seattle, Washington, USA.
Insights
Edoxaban shows promise as an alternative anticoagulant for preventing blood clots in children with heart conditions, demonstrating low bleeding and thrombotic event rates. This offers a convenient once-daily oral option with less monitoring compared to standard treatments.
Area of Science:
- Pediatric Cardiology
- Pharmacology
- Clinical Trials
Background:
- Standard anticoagulation for pediatric thromboembolism (TE) prevention involves low molecular weight heparins or vitamin K antagonists.
- Limited data exists on the use of direct oral anticoagulants (DOACs) in pediatric populations with cardiac disease.
Purpose of the Study:
- To evaluate the safety and efficacy of edoxaban for TE prevention in pediatric patients with cardiac disease.
- To compare edoxaban with standard of care (SOC) anticoagulation in this population.
Main Methods:
- A Phase 3, multinational, prospective, randomized, open-label, blinded-endpoint trial (ENNOBLE-ATE) was conducted in patients under 18 with cardiac disease.
- Patients were randomized 2:1 to receive oral edoxaban or SOC for 3 months, with an option for a 1-year extension.
- Primary endpoint was clinically relevant bleeding (CRB); secondary endpoint was symptomatic TE or asymptomatic intracardiac thrombosis.
Main Results:
- In the main study period, one nonmajor CRB occurred in each group.
- Treatment-emergent adverse events were reported in 46.8% of the edoxaban group and 41.4% of the SOC group.
- During the extension, 1 CRB and 4 TEs (including strokes and thromboses in Kawasaki disease patients) occurred among 147 children on edoxaban.
Conclusions:
- Edoxaban presents a potential alternative for thromboprophylaxis in pediatric cardiac patients.
- It demonstrated low rates of clinically relevant bleeding and thrombotic events.
- Advantages include once-daily dosing and infrequent monitoring requirements.
Background:
Standard of care (SOC) anticoagulation for thromboembolism (TE) prevention in children with cardiac disease includes low molecular weight heparins or vitamin K antagonists. Limited data exists for alternate use of direct oral anticoagulants in children.
Objectives:
The investigators aimed to obtain safety and efficacy data for edoxaban in children.
Methods:
We performed a phase 3, multinational, prospective, randomized, open-label, blinded-endpoint trial in patients <18 years of age with cardiac disease (ENNOBLE-ATE [Edoxaban for Prevention of Blood Vessels Being Blocked by Clots (Thrombotic Events) in Children at Risk Because of Cardiac Disease] trial). Patients were randomized 2:1 to age- and weight-based oral edoxaban once daily vs SOC for 3 months (main study period), stratified by cardiac diagnosis. Both groups could continue in an open-label edoxaban extension arm through 1 year. The primary endpoint was adjudicated clinically relevant bleeding (CRB). The main secondary endpoint was symptomatic TE or asymptomatic intracardiac thrombosis.
Results:
The modified intention-to-treat cohort included 167 children. One patient per group experienced a nonmajor CRB in the main period. Treatment-emergent adverse events occurred in 46.8% (51 of 109) with edoxaban and 41.4% (24 of 58) with SOC. One SOC patient experienced 2 TE events (DVT with PE). Among 147 children in the extension, 1 CRB event (0.7%) and 4 TEs occurred (2.8%; 2 strokes and 2 of 33 Kawasaki disease patients with coronary artery thromboses and/or myocardial infarctions).
Conclusions:
Edoxaban is a potential alternative mode of thromboprophylaxis in children with cardiac disease showing low rates of CRB and TEs with advantages of once daily dosing and infrequent monitoring requirement. (ENNOBLE-ATE [Edoxaban for Prevention of Blood Vessels Being Blocked by Clots] (Thrombotic Events) in Children at Risk Because of Cardiac Disease trial; NCT03395639).
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