In pediatric patients with cardiac disease at risk for thromboembolism (TE), treatment with edoxaban provides an appropriate alternative to standard-of-care (SOC) anticoagulants for the prevention of TE events, according to study results published in the Journal of the American College of Cardiology.
The ENNOBLE-ATE (Edoxaban for Prevention of Blood Vessels Being Blocked by Clots [Thrombotic Events] in Children at Risk Because of Cardiac Disease; ClinicalTrials.gov identifier: NCT03395639) trial is a phase 3, multinational, prospective, randomized, open-label, blinded-endpoint trial conducted in patients younger than 18 years of age with cardiac disease. All study participants were randomly assined in a 2:1 ratio to once-daily age-based/weight-based edoxaban or SOC for 3 months, stratified by cardiac diagnosis. Both treatment groups could continue in an open-label edoxaban extension arm through 1 year.
The primary study endpoint (safety) of ENNOBLE-ATE was adjudicated clinically relevant bleeding (CRB) within 3 months. The main secondary study endpoint (efficacy) was a composite of adjudicated symptomatic TE or asymptomatic cardiac thrombosis, as established by protocol-driven echocardiograms. Symptomatic TE included deep vein thrombosis (DVT), systemic arterial TE (including stroke), intracardiac thrombosis, myocardial infarction (MI), or pulmonary arterial TE (pulmonary embolism [PE]) associated with signs/symptoms that corresponded to the TE event.
ENNOBLE-ATE used a modified intention-to-treat (mITT) design, which included all patients who received the study drug for the main treatment period. All analyses performed were based on the study drug that the participant was randomized to receive.
A total of 167 children were included in the mITT cohort, with 109 assigned to the edoxaban treatment group and 58 to the SOC group. Results of the study showed that in the main study period, 1 patient per group experienced a nonmajor CRB. Treatment-emergent adverse events were reported in 46.8% of edoxaban-treated participants vs 41.4% of SOC-treated participants. In the SOC group, 1 patient experienced 2 TE events (DVT with PE).
Among a total of 147 pediatric patients in the extension period, only 1 CRB event (0.7%) occurred, which was associated with trauma. Additionally in the study extension, 4 TEs were reported (2.8%; 2 strokes and 2 of 33 patients with Kawasaki disease with coronary artery thromboses and/or MIs).
There are limitations of this study. The analysis was neither designed nor powered to detect superiority or noninferiority of edoxaban vs SOC anticoagulants. Additionally, because the final year was conducted during the beginning of the worldwide COVID-19 pandemic, on-site study visits, collection of data, and assessment of drug compliance were affected.
”…the trial findings indicate that edoxaban provides an appropriate alternative to SOC anticoagulants for the prevention of TE events in children with cardiac disease at risk for TE,” the study authors wrote. “Edoxaban provided once daily would remove stress and burden on families with children, who require thromboprophylaxis.”
Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Portman MA, Jacobs JP, Newburger JW, et al; on behalf of the ENNOBLE-ATE Trial Investigators. Edoxaban for thromboembolism prevention in pediatric patients with cardiac disease. J Am Coll Cardiol. Published online October 31, 2022. doi:10.1016/j.jacc.2022.09.031