Aortic Valve StenosisPhase 3REDOX-TAVINCT04171726

Rotterdam EDOXaban Leaflet Evaluation in Patients After Transcatheter Aortic Valve Implantation

A Phase 3 study testing Edoxaban in people with Aortic Valve Stenosis, run by Erasmus Medical Center at 1 site in Netherlands.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Aortic Valve Stenosis
What is being tested?: Edoxaban
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 100 participants
Where: 1 siteNetherlands
Study dates: 1 Aug 2019to 1 Sep 2023
Phase: Phase 3
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Show all 14Show fewer

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

Who cannot join

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

Show all 18Show fewer

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

Trial locations and contacts

1 site in 1 country.

Nicolas M Van Mieghem, MD, PhD contact

+31(0)107035260

n.vanmieghem@erasmusmc.nl

Maarten P van Wiechen, MD contact

+31(0)107038896

m.vanwiechen@erasmusmc.nl

Netherlands1 site, 1 recruiting

Erasmus MC
Rotterdam, 3015GD
Nicolas M van Mieghem, MD, PhD, +31(0)107035260, n.vanmieghem@erasmusmc.nl
Recruiting

Other trials in Netherlands

About this study

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.

Read the 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.

Conditions: Aortic Valve Stenosis
Being tested: Edoxaban
Keywords: Thrombosis, Aortic Valve Stenosis, Heart Valve Diseases, Ventricular Outflow Obstruction, Cardiovascular Diseases, Embolism and Thrombosis, Vascular Diseases, Heart Diseases, Factor Xa Inhibitors, Anticoagulants
Medical subject headings: Aortic Valve Stenosis, Thrombosis, Heart Valve Diseases, Ventricular Outflow Obstruction, Cardiovascular Diseases, Embolism and Thrombosis, Vascular Diseases, Heart Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EdoxabanDrug
A non-vitamin K antagonist (VKA) oral anticoagulant that selectively inhibits factor Xa.

Study groups in NCT04171726
Study group	Role	What they receive
Edoxaban	Experimental	treatment with edoxaban Receives: Drug: Edoxaban

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 3 months after TAVI

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Aug 20191 Sep 2023

First posted21 Nov 2019
Study start1 Aug 2019
Primary completion1 Jun 2023 (estimated)
Study completion1 Sep 2023 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (5)Papers the sponsor has linked to this study.
Other trials for Aortic Valve StenosisStudies of the same condition, open and under way.
More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 100 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04171726
Sponsor's protocol ID: REDOX TAVI
Acronym: REDOX-TAVI
Status last verified: Jul 2022
First submitted: 19 Nov 2019
Last updated: 27 Jul 2022
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

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.
PubMed 26436963
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.
PubMed 28838044
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.
PubMed 28330690
Adrichem R, van Wiechen MP, Knol WG, Hokken TW, Ooms JF, van den Dorpel MMP, Verhemel S, Kardys I, Nuis RJ, Daemen J, Hirsch A, Budde RPJ, Van Mieghem NM. Edoxaban Monotherapy and Incidence of Transcatheter Heart Valve Leaflet Thrombosis - The Rotterdam Edoxaban (REDOX) Study. Catheter Cardiovasc Interv. 2025 Feb;105(2):375-384. doi: 10.1002/ccd.31300. Epub 2024 Nov 22.
PubMed 39575924
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.
PubMed 35787831

Want to know more?

Nicolas M Van Mieghem, MD, PhD

+31(0)107035260

n.vanmieghem@erasmusmc.nl

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Trial of the F2 Filter and Delivery System for Embolic Protection During TAVR
Aortic Stenosis Treated With TAVI, Aortic Diseases
Not yet recruiting
Human Experimental Models of Pain (HEMP)
Acute Pain
Active, not recruitingObservational study
Intravascular Lithotripsy in High Risk Calcified Iliac Anatomy for Transfemoral TAVR
Iliac Disease, Aortic Valve Stenosis
Not yet recruiting
NHLBI SESAME (SEptal Scoring Along Midline Endocardium) Multi-Center Prospective Study Using Improvised Off-Label Devices
Hypertrophic Cardiomyopathy, Left Ventricular Outflow Obstruction
Recruiting
Exercise and Diet Supplements for Older Patients Undergoing TAVI: the IRON-TAVI Trial
Aortic Stenosis Disease, Aortic Stenosis Symptomatic

All Aortic Valve Stenosis trials

Study at a glance

From the registry record, last updated by the sponsor on 27 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Rotterdam EDOXaban Leaflet Evaluation in Patients After Transcatheter Aortic Valve Implantation
ClinicalTrials.gov ID: NCT04171726
Acronym / sponsor ID: REDOX-TAVI / REDOX TAVI
Conditions: Aortic Valve Stenosis
Keywords: Thrombosis, Aortic Valve Stenosis, Heart Valve Diseases, Ventricular Outflow Obstruction, Cardiovascular Diseases, Embolism and Thrombosis, Vascular Diseases, Heart Diseases
Phase: Phase 3
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 100 participants (estimated)
Lead sponsor: Erasmus Medical CenterUniversity, hospital or other
Collaborators: Daiichi Sankyo
Study start: 1 Aug 2019 (actual)
Primary completion: 1 Jun 2023 (estimated)
Study completion: 1 Sep 2023 (estimated)
First posted: 21 Nov 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

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.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Edoxaban	Experimental	Drug: Edoxabantreatment with edoxaban

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (14 listed)

Completed successful elective TAVI for severe native aortic valve stenosis with any commercially-available transcatheter heart valve (THV).
No periprocedural complications.
No formal indication for oral anticoagulation

Key exclusion criteria (18 listed)

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
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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EdoxabanA non-vitamin K antagonist (VKA) oral anticoagulant that selectively inhibits factor Xa.	Drug	Edoxaban

Primary outcome

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

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2022.
Background: PubMed 26436963Makkar 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.
Background: PubMed 28838044Sondergaard 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.
Background: PubMed 28330690Chakravarty 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.
Derived from this study: PubMed 39575924Adrichem R, van Wiechen MP, Knol WG, Hokken TW, Ooms JF, van den Dorpel MMP, Verhemel S, Kardys I, Nuis RJ, Daemen J, Hirsch A, Budde RPJ, Van Mieghem NM. Edoxaban Monotherapy and Incidence of Transcatheter Heart Valve Leaflet Thrombosis - The Rotterdam Edoxaban (REDOX) Study. Catheter Cardiovasc Interv. 2025 Feb;105(2):375-384. doi: 10.1002/ccd.31300. Epub 2024 Nov 22.
Derived from this study: PubMed 35787831van 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.
Individual participant dataSharing planned: No

Related trials for Aortic Valve Stenosis

Recruiting
Trial of the F2 Filter and Delivery System for Embolic Protection During TAVR
Aortic Stenosis Treated With TAVI, Aortic Diseases
Not yet recruiting
Human Experimental Models of Pain (HEMP)
Acute Pain
Active, not recruitingObservational study
Intravascular Lithotripsy in High Risk Calcified Iliac Anatomy for Transfemoral TAVR
Iliac Disease, Aortic Valve Stenosis
Not yet recruiting
NHLBI SESAME (SEptal Scoring Along Midline Endocardium) Multi-Center Prospective Study Using Improvised Off-Label Devices
Hypertrophic Cardiomyopathy, Left Ventricular Outflow Obstruction
Recruiting
Exercise and Diet Supplements for Older Patients Undergoing TAVI: the IRON-TAVI Trial
Aortic Stenosis Disease, Aortic Stenosis Symptomatic

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Nicolas M Van Mieghem, MD, PhD contact

+31(0)107035260

n.vanmieghem@erasmusmc.nl

Maarten P van Wiechen, MD contact

+31(0)107038896

m.vanwiechen@erasmusmc.nl

Nicolas M Van Mieghem, MD, PhD principal investigator

Erasmusm MC

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Edoxaban in people with Aortic Valve Stenosis, run by Erasmus Medical Center at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 27 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Nicolas M Van Mieghem, MD, PhD (+31(0)107035260, n.vanmieghem@erasmusmc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of aortic valve leaflet thickening after TAVI as assessed by cardiac 4D computed tomography scan (4DCT) (time frame: 3 months after TAVI). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04171726, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2022.