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

Primary Purpose

Aortic Valve Stenosis

Status
Recruiting
Phase
Phase 3
Locations
Netherlands
Study Type
Interventional
Intervention
Edoxaban
Sponsored by
Erasmus Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Aortic Valve Stenosis focused on measuring Thrombosis, Aortic Valve Stenosis, Heart Valve Diseases, Ventricular Outflow Obstruction, Cardiovascular Diseases, Embolism and Thrombosis, Vascular Diseases, Heart Diseases, Factor Xa Inhibitors, Anticoagulants

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Erasmus MCRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Edoxaban

Arm Description

treatment with edoxaban

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
November 19, 2019
Last Updated
July 25, 2022
Sponsor
Erasmus Medical Center
Collaborators
Daiichi Sankyo, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04171726
Brief Title
Rotterdam EDOXaban Leaflet Evaluation in Patients After Transcatheter Aortic Valve Implantation
Acronym
REDOX-TAVI
Official Title
Rotterdam EDOXaban Leaflet Evaluation in Patients After Transcatheter Aortic Valve Implantation
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 1, 2019 (Actual)
Primary Completion Date
June 1, 2023 (Anticipated)
Study Completion Date
September 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Erasmus Medical Center
Collaborators
Daiichi Sankyo, Inc.

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aortic Valve Stenosis
Keywords
Thrombosis, Aortic Valve Stenosis, Heart Valve Diseases, Ventricular Outflow Obstruction, Cardiovascular Diseases, Embolism and Thrombosis, Vascular Diseases, Heart Diseases, Factor Xa Inhibitors, Anticoagulants

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Edoxaban
Arm Type
Experimental
Arm Description
treatment with edoxaban
Intervention Type
Drug
Intervention Name(s)
Edoxaban
Intervention Description
A non-vitamin K antagonist (VKA) oral anticoagulant that selectively inhibits factor Xa.
Primary Outcome Measure Information:
Title
Incidence of aortic valve leaflet thickening after TAVI as assessed by cardiac 4D computed tomography scan (4DCT)
Description
total of participants with aortic valve thickening after TAVI
Time Frame
3 months after TAVI

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nicolas M Van Mieghem, MD, PhD
Phone
+31(0)107035260
Email
n.vanmieghem@erasmusmc.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Maarten P van Wiechen, MD
Phone
+31(0)107038896
Email
m.vanwiechen@erasmusmc.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicolas M Van Mieghem, MD, PhD
Organizational Affiliation
Erasmusm MC
Official's Role
Principal Investigator
Facility Information:
Facility Name
Erasmus MC
City
Rotterdam
ZIP/Postal Code
3015GD
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicolas M van Mieghem, MD, PhD
Phone
+31(0)107035260
Email
n.vanmieghem@erasmusmc.nl

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
26436963
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, 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.
Results Reference
background
PubMed Identifier
28838044
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.
Results Reference
background
PubMed Identifier
28330690
Citation
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.
Results Reference
background
PubMed Identifier
35787831
Citation
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.
Results Reference
derived

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Rotterdam EDOXaban Leaflet Evaluation in Patients After Transcatheter Aortic Valve Implantation

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