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)

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

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