Brief Title
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
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.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Rate of Patients With at Least One Prosthetic Leaflet With >50% Motion Reduction as Assessed by Cardiac 4DCT-scan
Secondary Outcome
The Rate of Prosthetic Leaflets With > 50% Motion Reduction as Assessed by Cardiac 4DCT-scan
Condition
Aortic Valve Stenosis
Intervention
Acetylsalicylic acid
Study Arms / Comparison Groups
ASA + Clopidogrel
Description: ASA (Acetylsalicylic acid) 75-100mg + Clopidogrel 75mg for 90 days, followed by ASA 75-100mg monotherapy
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
231
Start Date
May 2016
Completion Date
March 6, 2019
Primary Completion Date
December 2018
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Lars Søndergaard, MD;DMSc, ,
Location Countries
Canada
Location Countries
Canada
Administrative Informations
NCT ID
NCT02833948
Organization ID
ECRI 006 - H-15016807
Responsible Party
Sponsor
Study Sponsor
ECRI bv
Collaborators
Rigshospitalet, Denmark
Study Sponsor
Lars Søndergaard, MD;DMSc, Principal Investigator, Rigshospitalet, Denmark
Verification Date
January 2020