Clinical trial NCT02833948: 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)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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
Lead sponsor: ECRI bv
Sponsor class: INDUSTRY
Collaborators: name: Rigshospitalet, Denmark
name: Bayer
name: Cardialysis BV
First posted: 2016-07-14
Enrollment: 231
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

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 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

Primary outcomes:
measure: Rate of Patients With at Least One Prosthetic Leaflet With >50% Motion Reduction as Assessed by Cardiac 4DCT-scan
timeFrame: 3 months
Secondary outcomes:
measure: The Rate of Prosthetic Leaflets With > 50% Motion Reduction as Assessed by Cardiac 4DCT-scan
timeFrame: 3 months
measure: The Rate of Patients With at Least One Prosthetic Leaflet With Thickening as Assessed by Cardiac 4DCT-scan
timeFrame: 3 months
measure: The Rate of Prosthetic Leaflets With Thickening as Assessed by Cardiac 4DCT-scan
timeFrame: 3 months
measure: Aortic Transvalvular Mean Pressure Gradient (mmHg) as Determined by Transthoracic Echocardiography.
timeFrame: 3 months
measure: Effective Orifice Area (cm^2) as Determined by Transthoracic Echocardiography.
timeFrame: 3 months
measure: Death Assessed in the Main GALILEO Study and Analyzed in the GALILEO-4D Substudy With Regards to Occurence of the Leaflet Abnormalities (HALT) - as Exploratory Analysis.
timeFrame: 3 months
measure: Death Assessed in the Main GALILEO Study and Analyzed in the GALILEO-4D Substudy With Regards to Occurence of the Leaflet Abnormalities (RLM)- as Exploratory Analysis.
timeFrame: 3 months
measure: Thromboembolic Event Assessed in the Main GALILEO Study and Analyzed in the GALILEO-4D Substudy With Regards to Occurence of the Leaflet Abnormalities (HALT)- as Exploratory Analysis.
timeFrame: 3 months
measure: Thromboembolic Event Assessed in the Main GALILEO Study and Analyzed in the GALILEO-4D Substudy With Regards to Occurence of the Leaflet Abnormalities (RLM) - as Exploratory Analysis.
timeFrame: 3 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: New York
country: United States
facility: Mount Sinai M.C
state: New York
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas, Health Science Center
state: Texas
city: Edmonton
country: Canada
facility: University of Alberta Hospital
city: Vancouver
country: Canada
facility: Providence Health Care
city: Aarhus
country: Denmark
facility: Aarhus university hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Odense
country: Denmark
facility: Odense University Hospital
city: Bad Nauheim
country: Germany
facility: Kerckhoff Klinik GmbH
city: Berlin
country: Germany
facility: Charité- Universitätsmedizin Berlin - Campus Mitte
city: Berlin
country: Germany
facility: Deutsches Herzzentrum Berlin
city: Dortmund
country: Germany
facility: St. Johannes Hospital
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Lahr
country: Germany
facility: Medicin Herzzentrum Lahr/Baden
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig - Universitätsklinik
city: München
country: Germany
facility: Deutsches Herzzentrum München
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Breda
country: Netherlands
facility: Amphia Zienkenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus M.C
city: Lund
country: Sweden
facility: Skåne University Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Bern
country: Switzerland
facility: Inselspital
Study officials:
affiliation: Rigshospitalet, Denmark
name: Lars Søndergaard, MD;DMSc
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.