Rotterdam EDOXaban Leaflet Evaluation in Patients After Transcatheter Aortic Valve Implantation

Phase 3

• Conditions: Aortic Valve Stenosis
• Interventions: Drug: Edoxaban

• Registration Number: NCT04171726
• Lead Sponsor: Erasmus Medical Center

Brief Summary

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

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.

Study Timeline

• Study Start: 2019-08-01
• Study First Submitted: 2019-11-19
• Study First Submitted QC: 2019-11-19
• Study First Posted: 2019-11-21
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-25
• Last Update Posted: 2022-07-27
• Primary Completion: 2023-06-01
• Study Completion: 2023-09-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Edoxaban	Edoxaban	treatment with edoxaban

Primary Outcome Measures

Name	Time	Method
Incidence of aortic valve leaflet thickening after TAVI as assessed by cardiac 4D computed tomography scan (4DCT)	3 months after TAVI	total of participants with aortic valve thickening after TAVI

Trial Locations

Locations (1)

Erasmus MC; 🇳🇱 Rotterdam, Netherlands