Rotterdam EDOXaban Leaflet Evaluation in Patients After Transcatheter Aortic Valve Implantation

Study Overview
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Brief Summary
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A single-center, investigator-initiated, single arm interventional study in patients undergoing transfemoral transcatheter aortic valve replacement (TAVR) in the Erasmus Medical Center in Rotterdam (NL). Study population will be patients undergoing TAVR with no formal indication for oral anticoagulant (OAC) and no dual antiplatelet therapy (DAPT) requirement for coronary stents. Primary endpoint is the incidence of leaflet thickening on MSCT after three months of edoxaban treatment.

Detailed Description
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Rationale: Thromboembolic- and bleeding events can occur after TAVI and can have great consequences. There is currently no evidence-based guideline on prevention of thromboembolic events after TAVI and the current standard of care with DAPT 3-6 months is based on expert opinion. Recently multislice computed tomography (MSCT) studies identified bioprosthesis leaflet thickening and impaired leaflet motion after TAVI. The goal of this study is to investigate whether in TAVI patients, treatment with edoxaban leads to a reduction in leaflet thickening incidence after 3 months and whether it is safe and clinically efficient. Objective: To investigate whether treatment with edoxaban leads to a decrease in incidence of leaflet thickening and is clinical efficient and safe. Study design: A single-center, investigator-initiated, open-label, observational study. Study population: Patients undergoing transfemoral transcatheter aortic valve replacement in the Erasmus University Medical Center with no formal novel oral anticoagulants/vitamin-K-antagonist (NOAC/VKA) indication. Intervention (if applicable): Patients will be treated with edoxaban for a period of 3 months following TAVI. Afterwards they will switch to acetylsalicylic acid. Main study parameters/endpoints: The incidence of leaflet thickening on MSCT 3 months after TAVI and edoxaban treatment. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Thus far edoxaban has proven to be safe and non-inferior to treatment with warfarin in several indications. The role of anticoagulant agents in TAVI still has to be unravelled. Subjects participating in this trial are possibly at higher risk for bleeding complications than patients being treated with dual antiplatelet therapy after TAVI.

Official Title
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Rotterdam EDOXaban Leaflet Evaluation in Patients After Transcatheter Aortic Valve Implantation

Conditions
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Aortic Valve Stenosis

Intervention / Treatment
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* Drug: Edoxaban


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completed successful elective TAVI for severe native aortic valve stenosis with any commercially-available transcatheter heart valve (THV). Correct positioning of a single prosthetic heart valve Device success, defined by: Mean aortic valve gradient < 20 mmHg Peak transvalvular velocity < 3.0 m/s Aortic valve regurgitation of 2 or less No periprocedural complications. No overt stroke No uncontrolled bleeding No major vascular complication defined by the Valve academic research committee 2 (VARC-2) consensus No formal indication for oral anticoagulation Prevention of thromboembolic complications in patients with atrial fibrillation Prevention for recurrent venous thromboembolism Prevention for recurrent pulmonary embolism Exclusion Criteria: History of life-threatening or major bleeding event ≥ Bleeding academic research committee (BARC) 3b definitions within the last year. Conditions with a high risk of bleeding Active peptic ulcer or upper gastrointestinal bleeding (< 3 months) Malignancy with high risk of bleeding Recent unresolved brain of spinal injury Spinal or ophthalmic surgery within last 3 months prior to enrolment Intracranial haemorrhage Esophagal varices Arteriovenous malformations with high risk of bleeding Vascular aneurysms Major intraspinal or intracerebral vascular abnormalities Hypersensitivity or contraindications to edoxaban No percutaneous coronary intervention within 6 months prior to randomization (requiring DAPT after TAVR) Dialysis-dependency or glomerular filtration rate < 30 mL/min at time of enrollment Active bleeding or bleeding diathesis including thrombocytopenia (platelet count < 50.000 cells/UL), thromboasthenia, haemophilia or von Willebrand disease Patients unable to adhere to or complete the investigational protocol for any reason including but not limited to geographical residence, psychiatric condition or life-threatening disease Pregnant or breast-feeding subjects Current participation in clinical trials that potentially interfere with the current study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Edoxaban<br>treatment with edoxaban | Drug: Edoxaban<br>* A non-vitamin K antagonist (VKA) oral anticoagulant that selectively inhibits factor Xa.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of aortic valve leaflet thickening after TAVI as assessed by cardiac 4D computed tomography scan (4DCT) | total of participants with aortic valve thickening after TAVI | 3 months after TAVI | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thrombosis, Aortic Valve Stenosis, Heart Valve Diseases, Ventricular Outflow Obstruction, Cardiovascular Diseases, Embolism and Thrombosis, Vascular Diseases, Heart Diseases, Factor Xa Inhibitors, Anticoagulants