Comparison of a Rivaroxaban-based Strategy With an Antiplatelet-based Strategy Following Successful TAVR for the Prevention of Leaflet Thickening and Reduced Leaflet Motion as Evaluated by Four-dimensional, Volume-rendered Computed Tomography (4DCT)

NCT02833948 | Completed Phase 3 Results DMC

• 1 other identifier: ECRI 006 - H-15016807
• Study Type: interventional
• Target: 231
• Locations: 7 countries
• Sites: 25

Brief Summary

The aortic valve is located between the left ventricle and the aorta. Patients with symptomatic, severe aortic valve stenosis conventionally have it surgically replaced requiring direct access to the heart through the chest. Transcatheter aortic valve replacement (TAVR) is now a well-established alternative for treating severe aortic valve stenosis. Both types of intervention improve prognosis and alleviate symptoms. The optimal choice of blood thinning therapy after TAVR is unknown. It has been reported that leaflet thrombosis with reduced leaflet motion can occur and this phenomenon has been suggested to be potentially related with neurological events. In addition, the occurence of this phenomenon can be reduced with anticoagulation blood thinning therapy. The purpose of this study is to evaluate if anticoagulation compared to the usual double platelet inhibitor therapy after TAVR can reduce the risk of leaflet thrombosis.

Conditions

Aortic Valve Stenosis; Cardiovascular Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Thrombosis

Keywords

Heart Valve Disease; Randomized Controlled Trial; Transcatheter Aortic Valve Replacement; TAVR; Valve Thrombosis

Outcome Measures

Primary Outcomes (1)

• Rate of Patients With at Least One Prosthetic Leaflet With >50% Motion Reduction as Assessed by Cardiac 4DCT-scan

  Reduced systolic leaflet excursion is classified as: (I) normal, (II) mildly reduced (\<50%), (III) moderate to severely reduced (\>50%), and (IV) immobile. Reduced systolic leaflet excursion is considered significant when it is \> 50% or immobile. Quantitative assessment of leaflet motion is performed with a blood pool inversion volume rendered cine reconstruction throughout the cardiac cycle evaluating the bioprosthetic leaflets.

  3 months

Secondary Outcomes (9)

• The Rate of Prosthetic Leaflets With > 50% Motion Reduction as Assessed by Cardiac 4DCT-scan

  3 months

• The Rate of Patients With at Least One Prosthetic Leaflet With Thickening as Assessed by Cardiac 4DCT-scan

  3 months

• The Rate of Prosthetic Leaflets With Thickening as Assessed by Cardiac 4DCT-scan

  3 months

• Aortic Transvalvular Mean Pressure Gradient (mmHg) as Determined by Transthoracic Echocardiography.

  3 months

• Effective Orifice Area (cm^2) as Determined by Transthoracic Echocardiography.

  3 months

Study Arms (2)

ASA + Clopidogrel

ACTIVE COMPARATOR

ASA (Acetylsalicylic acid) 75-100mg + Clopidogrel 75mg for 90 days, followed by ASA 75-100mg monotherapy

Drug: Acetylsalicylic acid; Drug: Clopidogrel

Rivaroxaban + ASA

EXPERIMENTAL

Rivaroxaban 10mg + ASA 75-100mg for 90 days, followed by rivaroxaban 10mg monotherapy

Drug: Acetylsalicylic acid; Drug: Rivaroxaban

Interventions

Acetylsalicylic acid DRUG

Drug: Acetylsalicylic acid: 75 - 100 mg OD (for first 90 days only in arm 1)

Also known as: Asprin

ASA + Clopidogrel; Rivaroxaban + ASA

Clopidogrel DRUG

Drug: Clopidogrel 75 mg OD for first 90 days

Also known as: Plavix

ASA + Clopidogrel

Rivaroxaban DRUG

Drug: Rivaroxaban (Xarelto): 10 mg OD (once-daily)

Also known as: Xarelto

Rivaroxaban + ASA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Successful TAVR of a native aortic valve stenosis
• By iliofemoral or subclavian access
• With any approved/marketed TAVR device
• Written informed consent

You may not qualify if:

• Atrial fibrillation (AF), current or previous, with an ongoing indication for oral anticoagulant treatment
• Any other indication for continued treatment with any oral anticoagulant
• Known bleeding diathesis (such as but not limited to platelet count ≤ 50,000/mm3 at screening, hemoglobin level \< 8.5 g/dL or \< 5.3 mmol/l, history of intracranial hemorrhage, or subdural hematoma)
• Any indication for dual antiplatelet therapy (DAPT) for more than three months after randomization (such as coronary, carotid, or peripheral stent implantation)
• Clinically overt stroke within the last three months
• Planned coronary or vascular intervention or major surgery
• Severe renal insufficiency (eGFR \< 30 mL/min/1.73 m2) or on dialysis, or post-TAVR unresolved acute kidney injury with renal dysfunction ≥ stage 2
• Moderate and severe hepatic impairment (Child-Pugh Class B or C) or any hepatic disease associated with coagulopathy
• Iodine contrast allergy or other condition that prohibits CT imaging

Sponsors & Collaborators

• ECRI bv: lead
• Rigshospitalet, Denmark: collaborator
• Bayer: collaborator
• Cardialysis BV: collaborator

Study Sites (25)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Mount Sinai M.C

New York, New York, 10029-6574, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Texas, Health Science Center

Houston, Texas, 78229, United States

Location

University of Alberta Hospital

Edmonton, AB T6G 2B7, Canada

Location

Providence Health Care

Vancouver, ON M1L 1W1, Canada

Location

Aarhus university hospital

Aarhus, 8000, Denmark

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Odense University Hospital

Odense, 5000, Denmark

Location

Kerckhoff Klinik GmbH

Bad Nauheim, 61231, Germany

Location

Charité- Universitätsmedizin Berlin - Campus Mitte

Berlin, 10117, Germany

Location

Deutsches Herzzentrum Berlin

Berlin, 13353, Germany

Location

St. Johannes Hospital

Dortmund, 44137, Germany

Location

Universitätsklinikum Erlangen

Erlangen, 91012, Germany

Location

Universitätsklinikum Schleswig-Holstein

Kiel, 24105, Germany

Location

Medicin Herzzentrum Lahr/Baden

Lahr, 77933, Germany

Location

Herzzentrum Leipzig - Universitätsklinik

Leipzig, 04289, Germany

Location

Deutsches Herzzentrum München

München, 80636, Germany

Location

Academic Medical Center

Amsterdam, 1105, Netherlands

Location

Amphia Zienkenhuis

Breda, 4818, Netherlands

Location

Erasmus M.C

Rotterdam, 3015, Netherlands

Location

Skåne University Hospital

Lund, SE-205 02, Sweden

Location

Karolinska University Hospital

Stockholm, SE-171 76, Sweden

Location

University Hospital Basel

Basel, 4056, Switzerland

Location

Inselspital

Bern, 3010, Switzerland

Location

Related Publications (2)

• 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.

  PMID: 26436963 BACKGROUND

• De Backer O, Dangas GD, Jilaihawi H, Leipsic JA, Terkelsen CJ, Makkar R, Kini AS, Veien KT, Abdel-Wahab M, Kim WK, Balan P, Van Mieghem N, Mathiassen ON, Jeger RV, Arnold M, Mehran R, Guimaraes AHC, Norgaard BL, Kofoed KF, Blanke P, Windecker S, Sondergaard L; GALILEO-4D Investigators. Reduced Leaflet Motion after Transcatheter Aortic-Valve Replacement. N Engl J Med. 2020 Jan 9;382(2):130-139. doi: 10.1056/NEJMoa1911426. Epub 2019 Nov 16.

  PMID: 31733182 DERIVED

MeSH Terms

Conditions

Aortic Valve Stenosis; Cardiovascular Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Thrombosis

Interventions

Aspirin; acetylsalicylic acid lysinate; Clopidogrel; Rivaroxaban

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Diseases; Embolism and Thrombosis; Vascular Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Morpholines; Oxazines

Results Point of Contact

• Title: Ole De Backer, MD, PhD
• Organization: The Heart Center - Rigshospitalet, Copenhagen, Denmark

ole.debacker@gmail.com

+45-35457086

Study Officials

• Lars Søndergaard, MD;DMSc

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2016
• First Posted: July 14, 2016
• Study Start: May 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: March 6, 2019
• Last Updated: January 18, 2020
• Results First Posted: January 18, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

NL (3); US (4); DK (3); SE (2); CA (2); CH (2); DE (9)