Rotterdam EDOXaban Leaflet Evaluation in Patients After Transcatheter Aortic Valve Implantation (REDOX-TAVI)

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.

Study Overview

• Status: Recruiting
• Conditions: Aortic Valve Stenosis
• Intervention / Treatment: Drug: Edoxaban

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 Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Nicolas M van Mieghem, MD, PhD; Phone Number: +31(0)107035260; Email: n.vanmieghem@erasmusmc.nl
• Study Contact Backup: Name: Maarten P van Wiechen, MD; Phone Number: +31(0)107038896; Email: m.vanwiechen@erasmusmc.nl

Study Locations

• Netherlands
  • Rotterdam, Netherlands, 3015GD
    • Recruiting
    • Erasmus MC
    • Contact: Nicolas M van Mieghem, MD, PhD; Phone Number: +31(0)107035260; Email: n.vanmieghem@erasmusmc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Collaborators: Daiichi Sankyo, Inc.
• Investigators: Principal Investigator: Nicolas M Van Mieghem, MD, PhD, Erasmusm MC

Publications and helpful links

General Publications

• Makkar RR, Fontana G, Jilaihawi H, Chakravarty T, Kofoed KF, De Backer O, Asch FM, Ruiz CE, Olsen NT, Trento A, Friedman J, Berman D, Cheng W, Kashif M, Jelnin V, Kliger CA, Guo H, Pichard AD, Weissman NJ, Kapadia S, Manasse E, Bhatt DL, Leon MB, Sondergaard L. Possible Subclinical Leaflet Thrombosis in Bioprosthetic Aortic Valves. N Engl J Med. 2015 Nov 19;373(21):2015-24. doi: 10.1056/NEJMoa1509233. Epub 2015 Oct 5.
• Sondergaard L, De Backer O, Kofoed KF, Jilaihawi H, Fuchs A, Chakravarty T, Kashif M, Kazuno Y, Kawamori H, Maeno Y, Bieliauskas G, Guo H, Stone GW, Makkar R. Natural history of subclinical leaflet thrombosis affecting motion in bioprosthetic aortic valves. Eur Heart J. 2017 Jul 21;38(28):2201-2207. doi: 10.1093/eurheartj/ehx369.
• Chakravarty T, Sondergaard L, Friedman J, De Backer O, Berman D, Kofoed KF, Jilaihawi H, Shiota T, Abramowitz Y, Jorgensen TH, Rami T, Israr S, Fontana G, de Knegt M, Fuchs A, Lyden P, Trento A, Bhatt DL, Leon MB, Makkar RR; RESOLVE; SAVORY Investigators. Subclinical leaflet thrombosis in surgical and transcatheter bioprosthetic aortic valves: an observational study. Lancet. 2017 Jun 17;389(10087):2383-2392. doi: 10.1016/S0140-6736(17)30757-2. Epub 2017 Mar 19.
• van Wiechen MP, El Azzouzi I, Knol WG, Adrichem R, Hokken TW, Ooms JF, de Ronde-Tillmans MJ, Daemen J, de Jaegere PP, Hirsch A, Budde RPJ, Van Mieghem NM. Leaflet Thickening and Motion After Transcatheter Aortic Valve Replacement: Design and Rationale of the Rotterdam Edoxaban Trial. Cardiovasc Revasc Med. 2022 Nov;44:67-70. doi: 10.1016/j.carrev.2022.06.011. Epub 2022 Jun 17.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: November 19, 2019
• First Submitted That Met QC Criteria: November 19, 2019
• First Posted (Actual): November 21, 2019

Study Record Updates

• Last Update Posted (Actual): July 27, 2022
• Last Update Submitted That Met QC Criteria: July 25, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Vascular Diseases; Cardiovascular Diseases; Thrombosis; Aortic Valve Stenosis; Heart Diseases; Heart Valve Diseases; Anticoagulants; Factor Xa Inhibitors; Ventricular Outflow Obstruction; Embolism and Thrombosis
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Edoxaban
• Other Study ID Numbers: REDOX TAVI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No