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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)

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ClinicalTrials.gov Identifier: NCT02833948
Recruitment Status : Active, not recruiting
First Posted : July 14, 2016
Last Update Posted : October 19, 2018
Sponsor:
Collaborators:
Rigshospitalet, Denmark
Bayer
Cardialysis BV
Information provided by (Responsible Party):
ECRI bv

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.


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

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
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
Study Start Date : May 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : January 2019


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. 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 :
  1. The rate of prosthetic leaflets with > 50% motion reduction as assessed by cardiac 4DCT-scan [ Time Frame: 3 months ]
  2. The rate of patients with at least one prosthetic leaflet with thickening as assessed by cardiac 4DCT-scan [ Time Frame: 3 months ]
  3. The rate of prosthetic leaflets with thickening as assessed by cardiac 4DCT-scan [ Time Frame: 3 months ]
  4. Functional NYHA class. [ Time Frame: 3 months ]
  5. 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 ]
  6. Aortic transvalvular mean pressure gradient (mmHg) as determined by transthoracic echocardiography. [ Time Frame: 3 months ]
  7. Effective orifice area (cm^2) as determined by transthoracic echocardiography. [ Time Frame: 3 months ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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

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


Locations
United States, California
Cedars Sinai Medical Center
Los Angeles, California, United States, 90048
United States, New York
Mount Sinai M.C
New York, New York, United States, 10029-6574
United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
University of Texas, Health Science Center
Houston, Texas, United States, 78229
Canada
University of Alberta Hospital
Edmonton, Canada, AB T6G 2B7
Providence Health Care
Vancouver, Canada, ON M1L 1W1
Denmark
Aarhus university hospital
Aarhus, Denmark, 8000
Rigshospitalet
Copenhagen, Denmark, 2100
Odense University Hospital
Odense, Denmark, 5000
Germany
Kerckhoff Klinik GmbH
Bad Nauheim, Germany, 61231
Charité- Universitätsmedizin Berlin - Campus Mitte
Berlin, Germany, 10117
Deutsches Herzzentrum Berlin
Berlin, Germany, 13353
St. Johannes Hospital
Dortmund, Germany, 44137
Universitätsklinikum Erlangen
Erlange, Germany, 91012
Universitätsklinikum Schleswig-Holstein
Kiel, Germany, 24105
Medicin Herzzentrum Lahr/Baden
Lahr, Germany, 77933
Herzzentrum Leipzig - Universitätsklinik
Leipzig, Germany, 04289
Deutsches Herzzentrum München
München, Germany, 80636
Netherlands
Academic Medical Center
Amsterdam, Netherlands, 1105
Amphia Zienkenhuis
Breda, Netherlands, 4818
Erasmus M.C
Rotterdam, Netherlands, 3015
Sweden
Skåne University Hospital
Lund, Sweden, SE-205 02
Karolinska University Hospital
Stockholm, Sweden, SE-171 76
Switzerland
University Hospital Basel
Basel, Switzerland, 4056
Inselspital
Bern, Switzerland, 3010
Sponsors and Collaborators
ECRI bv
Rigshospitalet, Denmark
Bayer
Cardialysis BV
Investigators
Principal Investigator: Lars Søndergaard, MD;DMSc Rigshospitalet, Denmark

Publications:
Responsible Party: ECRI bv
ClinicalTrials.gov Identifier: NCT02833948     History of Changes
Other Study ID Numbers: ECRI 006 - H-15016807
First Posted: July 14, 2016    Key Record Dates
Last Update Posted: October 19, 2018
Last Verified: October 2018
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