Rotterdam EDOXaban Leaflet Evaluation in Patients After Transcatheter Aortic Valve Implantation

Aortic Valve Stenosis Clinical Trial

— REDOX-TAVI  

Official title:

Rotterdam EDOXaban Leaflet Evaluation in Patients After Transcatheter Aortic Valve Implantation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04171726
• Other study ID #: REDOX TAVI
• Status: Recruiting
• Phase: Phase 3
• Start date: August 1, 2019
• Est. completion date: September 1, 2023

Study information

• Verified date: July 2022
• Source: Erasmus Medical Center
• Contact: Nicolas M Van Mieghem, MD, PhD
• Phone: +31(0)107035260
• Email: n.vanmieghem[@]erasmusmc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: September 1, 2023
• Est. primary completion date: June 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aortic Valve Stenosis

Intervention

Drug:
• Edoxaban
A non-vitamin K antagonist (VKA) oral anticoagulant that selectively inhibits factor Xa.

Locations

Country	Name	City	State
Netherlands	Erasmus MC	Rotterdam

Sponsors (2)

Lead Sponsor	Collaborator
Erasmus Medical Center	Daiichi Sankyo, Inc.

Country where clinical trial is conducted

Netherlands, 

References & Publications (3)

Chakravarty T, Søndergaard L, Friedman J, De Backer O, Berman D, Kofoed KF, Jilaihawi H, Shiota T, Abramowitz Y, Jørgensen 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. — View Citation

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, Søndergaard 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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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