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)

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.

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