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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) (GALILEO-4D)

This study is currently recruiting participants.
Verified August 2017 by ECRI bv
Sponsor:
ClinicalTrials.gov Identifier:
NCT02833948
First Posted: July 14, 2016
Last Update Posted: August 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Rigshospitalet, Denmark
Bayer
Cardialysis BV
Information provided by (Responsible Party):
ECRI bv
  Purpose

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.


Condition Intervention Phase
Aortic Valve Stenosis Cardiovascular Diseases Heart Valve Diseases Ventricular Outflow Obstruction Thrombosis Drug: Acetylicsalicylic acid Drug: Clopidogrel Drug: Rivaroxaban Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: Randomized 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) - Substudy of the GALILEO-trial

Resource links provided by NLM:


Further study details as provided by ECRI bv:

Primary Outcome Measures:
  • Rate of patients with at least one prosthetic leaflet with >50% motion reduction as assessed by cardiac 4DCT-scan [ Time Frame: 3 months ]
    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.


Secondary Outcome Measures:
  • The rate of prosthetic leaflets with > 50% motion reduction as assessed by cardiac 4DCT-scan [ Time Frame: 3 months ]
  • The rate of patients with at least one prosthetic leaflet with thickening as assessed by cardiac 4DCT-scan [ Time Frame: 3 months ]
  • The rate of prosthetic leaflets with thickening as assessed by cardiac 4DCT-scan [ Time Frame: 3 months ]
  • Functional NYHA class. [ Time Frame: 3 months ]
  • Death, first thromboembolic event (DTE), and safety endpoints (see GALILEO trial) will be assessed in the main GALILEO study and analyzed in the GALILEO-4D substudy with regards to occurence of the leaflet abnormalities - as exploratory analysis. [ Time Frame: 3 months ]
  • Aortic transvalvular mean pressure gradient (mmHg) as determined by transthoracic echocardiography. [ Time Frame: 3 months ]
  • Effective orifice area (cm^2) as determined by transthoracic echocardiography. [ Time Frame: 3 months ]

Estimated Enrollment: 300
Study Start Date: May 2016
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ASA + Clopidogrel
ASA (Acetylsalicylic acid) 75-100mg + Clopidogrel 75mg for 90 days, followed by ASA 75-100mg monotherapy
Drug: Acetylicsalicylic acid

Drug: Acetylsalicylic acid:

75 - 100 mg OD (for first 90 days only in arm 1)

Other Name: Asprin
Drug: Clopidogrel
Drug: Clopidogrel 75 mg OD for first 90 days
Other Name: Plavix
Experimental: Rivaroxaban + ASA
Rivaroxaban 10mg + ASA 75-100mg for 90 days, followed by rivaroxaban 10mg monotherapy
Drug: Acetylicsalicylic acid

Drug: Acetylsalicylic acid:

75 - 100 mg OD (for first 90 days only in arm 1)

Other Name: Asprin
Drug: Rivaroxaban

Drug: Rivaroxaban (Xarelto):

10 mg OD (once-daily)

Other Name: Xarelto

Detailed Description:

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become an established therapeutic option for patients with symptomatic, severe aortic valve stenosis, who are ineligible or at high risk for conventional surgical aortic valve replacement (SAVR). It was recently reported that leaflet thickening and reduced leaflet motion, verified by four-dimensional computed tomography (4DCT), was not uncommon after both TAVR and SAVR. It has been emphasized that this phenomenon should be further investigated for its effect on clinical outcomes (e.g. stroke) and valve durability. As this valve leaflet thickening and reduced motion could be reversed by oral anticoagulant (OAC) treatment and was not observed in patients on chronic OAC therapy, it has been hypothesized that this phenomenon could be related to possible leaflet thrombosis or a "thrombotic film" on the leaflets.

AIM: To evaluate whether a rivaroxaban-based strategy, following successful TAVR, compared to an antiplatelet-based strategy, is superior in reducing subclinical valve leaflet thickening and motion abnormalities - as detected by 4DCT-scan.

POPULATION: All patients undergoing successful TAVR by ileofemoral or subclavian access with an approved TAVR device will be screened for eligibility. Included subjects must provide written informed consent. Inclusion and exclusion criteria are listed below.

DESIGN: The GALILEO-4D trial will be conducted as a substudy of the multicenter, open-label, randomized, event-driven, active-controlled GALILEO trial. Patients will be 1:1 randomized to an antiplatelet-based strategy vs. rivaroxaban-based strategy - the randomization will adopt the same 1:1 randomization of the main GALILEO trial. In case the GALILEO-4D trial should still be continued after completion of the main GALILEO trial, this 1:1 randomization will be continued until inclusion of 150 patients in both treatment groups. In total, 300 patients will be randomized in the GALILEO-4D trial.

INTERVENTION: Subjects in the GALILEO-4D substudy will receive the same intervention as in the main GALILEO study. In addition, a 4DCT-scan and echocardiography will be performed at 90 days after randomization.

END POINTS: The primary endpoint constitutes the rate of patients with at least one prosthetic leaflet with > 50% motion reduction as assessed by cardiac 4DCT-scan (total N = 300). The secondary endpoints are listed below.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02833948


Contacts
Contact: Lars Søndergaard, MD, DMSc +45 35452018 lars.soendergaard.01@regionh.dk
Contact: Ole De Backer, MD; PhD +45-35457086 ole.debacker@gmail.com

Locations
United States, California
Cedars Sinai Medical Center Not yet recruiting
Los Angeles, California, United States, 90048
Contact: Raj Makkar       raj.makkar@cshs.org   
Contact: Ole De Backer       ole.debacker@gmail.com   
United States, New York
Mount Sinai M.C Not yet recruiting
New York, New York, United States, 10029-6574
Contact: George Dangas       george.dangas@mountsinai.org   
Contact: Ole De Backer       ole.debacker@gmail.com   
United States, Pennsylvania
Hospital of the University of Pennsylvania Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
University of Texas, Health Science Center Not yet recruiting
Houston, Texas, United States, 78229
Canada
University of Alberta Hospital Not yet recruiting
Edmonton, Canada, AB T6G 2B7
Contact: Robert Welsh       Robert.Welsh@albertahealthservices.ca   
Contact: Ole De Backer       ole.debacker@gmail.com   
Providence Health Care Not yet recruiting
Vancouver, Canada, ON M1L 1W1
Contact: John Webb       webb@providencehealth.bc.ca   
Contact: Ole De Backer       ole.debacker@gmail.com   
Denmark
Aarhus university hospital Recruiting
Aarhus, Denmark, 8000
Contact: Christian J Therkelsen       christian.juhl.terkelsen@clin.au.dk   
Contact: Ole De Backer       ole.debacker@gmail.com   
Rigshospitalet Recruiting
Copenhagen, Denmark, 2100
Contact: Lars Søndergaard, MD; DMSc    +45-35458693    Lars.Soendergaard.01@regionh.dk   
Contact: Ole De Backer    +45-35457086    ole.debacker@gmail.com   
Odense University Hospital Recruiting
Odense, Denmark, 5000
Contact: Karsten Veien       karsten.veien@rsyd.dk   
Contact: Ole De Backer       ole.debacker@gmail.com   
Germany
Kerckhoff Klinik GmbH Not yet recruiting
Bad Nauheim, Germany, 61231
Contact: Kim Won-Keun       W.Kim@kerckhoff-klinik.de   
Contact: Ole De Backer       ole.debacker@gmail.com   
Charité- Universitätsmedizin Berlin - Campus Mitte Not yet recruiting
Berlin, Germany, 10117
Contact: Verena Stangl       verena.stangl@charite.de   
Contact: Ole De Backer       ole.debacker@gmail.com   
Deutsches Herzzentrum Berlin Not yet recruiting
Berlin, Germany, 13353
Contact: Jörg Kempfert       kempfert@dhzb.de   
Contact: Ole De Backer       ole.debacker@gmail.com   
St. Johannes Hospital Not yet recruiting
Dortmund, Germany, 44137
Contact: Helge Möllmann       moellmann@me.com   
Contact: Ole De Backer       ole.debacker@gmail.com   
Universitätsklinikum Erlangen Not yet recruiting
Erlange, Germany, 91012
Contact: Martin Arnold       martin.arnold@uk-erlangen.de   
Contact: Ole De Backer       ole.debacker@gmail.com   
Universitätsklinikum Schleswig-Holstein Not yet recruiting
Kiel, Germany, 24105
Contact: Norbert Frey       Norbert.Frey@uksh.de   
Contact: Ole De Backer       ole.debacker@gmail.com   
Medicin Herzzentrum Lahr/Baden Not yet recruiting
Lahr, Germany, 77933
Contact: Eberhard ulz Schulz       Eberhard.Schulz@unimedizin-mainz.de   
Contact: Ole De Backer       ole.debacker@gmail.com   
Herzzentrum Leipzig - Universitätsklinik Not yet recruiting
Leipzig, Germany, 04289
Contact: Axel Linke       Axel.Linke@medizin.uni-leipzig.de   
Contact: Ole De Backer       ole.debacker@gmail.com   
Deutsches Herzzentrum München Not yet recruiting
München, Germany, 80636
Contact: Christian Hengstenberg       christian.hengstenberg@gmail.com   
Contact: Ole De Backer       ole.debacker@gmail.com   
Netherlands
Academic Medical Center Not yet recruiting
Amsterdam, Netherlands, 1105
Contact: Robbert de Winter       r.j.dewinter@amc.uva.nl   
Contact: Ole De Backer       ole.debacker@gmail.com   
Amphia Zienkenhuis Not yet recruiting
Breda, Netherlands, 4818
Contact: Willem Dewilde, DMSc         
Contact: Ole De Backer       ole.debacker@gmail.com   
Erasmus M.C Not yet recruiting
Rotterdam, Netherlands, 3015
Contact: Nicolas M Van Mieghem       n.vanmieghem@erasmusmc.nl   
Contact: Ole De Backer       ole.debacker@gmail.com   
Sweden
Skåne University Hospital Not yet recruiting
Lund, Sweden, SE-205 02
Contact: Matthias Gotberg       matthias.gotberg@gmail.com   
Contact: Ole De Backer       ole.debacker@gmail.com   
Karolinska University Hospital Not yet recruiting
Stockholm, Sweden, SE-171 76
Contact: Andreas Ruck       andreas.ruck@karolinska.se   
Contact: Ole De Backer       ole.debacker@gmail.com   
Switzerland
University Hospital Basel Not yet recruiting
Basel, Switzerland, 4056
Contact: Raban Jeger       Raban.Jeger@usb.ch   
Contact: Ole De Backer       ole.debacker@gmail.com   
Inselspital Recruiting
Bern, Switzerland, 3010
Contact: Stephan Windecker       stephan.windecker@insel.ch   
Contact: Ole De Backer       ole.debacker@gmail.com   
Sponsors and Collaborators
ECRI bv
Rigshospitalet, Denmark
Bayer
Cardialysis BV
Investigators
Principal Investigator: Lars Søndergaard, MD;DMSc Rigshospitalet, Denmark
  More Information

Publications:
Responsible Party: ECRI bv
ClinicalTrials.gov Identifier: NCT02833948     History of Changes
Other Study ID Numbers: ECRI 006 - H-15016807
First Submitted: June 24, 2016
First Posted: July 14, 2016
Last Update Posted: August 11, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by ECRI bv:
Heart Valve Disease
Randomized Controlled Trial
Transcatheter Aortic Valve Replacement
TAVR
Valve Thrombosis

Additional relevant MeSH terms:
Cardiovascular Diseases
Thrombosis
Aortic Valve Stenosis
Heart Valve Diseases
Ventricular Outflow Obstruction
Embolism and Thrombosis
Vascular Diseases
Heart Diseases
Clopidogrel
Ticlopidine
Rivaroxaban
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Fibrinolytic Agents
Fibrin Modulating Agents
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Anticoagulants