Strategies to Prevent Transcatheter Heart Valve Dysfunction in Low Risk Transcatheter Aortic Valve Replacement

Study Overview
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Brief Summary
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100 subjects in the each of the treatment arms of the study (total 200 treatment arm subjects) and up to 100 subjects in the registry arm of the study.

Detailed Description
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This study aims to examine the optimal anticoagulation/antiplatelet regimen in low risk patients undergoing TAVR. The prospective randomized controlled arm of this study will assess the utility of short-term oral anticoagulation with warfarin compared to antiplatelet therapy alone after TAVR in low risk patients to reduce the incidence of structural valve deterioration manifest as clinical events, increased aortic valve gradients or transvalvular regurgitation, or subclinical leaflet thrombosis. Low risk subjects with symptomatic severe aortic stenosis will be enrolled to undergo TAVR. Following TAVR, subjects will be randomized to receive warfarin plus low dose Aspirin or low dose Aspirin monotherapy for 30-45 days. Subjects with other indications for anticoagulation (e.g. AF, DVT or PE) will not be randomized and instead will be followed in a separate registry arm. Baseline demographic, clinical, non-invasive imaging (echocardiography and CT), TAVR procedural details, clinical follow up data will be prospectively collected for all subjects. Echocardiography and contrast-enhanced 4D cardiac CT will be performed in all subjects between 30-45 days after TAVR to evaluate for evidence of structural valve deterioration. This multicenter prospective randomized study will enroll 200 consecutive low risk subjects with symptomatic severe aortic stenosis into the treatment arms of the study. Up to 100 additional subjects with a pre-existing indication for anticoagulation (e.g. atrial fibrillation, deep venous thrombosis or pulmonary embolism) or who are not eligible for randomization after TAVR due to development of a new indication for anticoagulation will be enrolled into the registry arm of the study. Inclusion of this registry arm will ensure that the secondary objective pooled analysis of patient level data from this study and the Low Risk TAVR (LRT) study, truly represents an all-comers cohort of low risk patients undergoing TAVR, and does not exclude a significant subgroup.

Official Title
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Strategies to Prevent Transcatheter Heart Valve Dysfunction in Low Risk Transcatheter Aortic Valve Replacement

Conditions
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Aortic Stenosis

Intervention / Treatment
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* Device: TAVR
* Other: Warfarin plus Aspirin
* Other: Aspirin Only


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe, degenerative AS, defined as: Mean aortic valve gradient ≥40 mm Hg OR Vmax ≥4 m/sec AND Calculated aortic valve area ≤1.0 cm2 OR aortic valve area index ≤0.6 cm2/m2 Symptomatic AS, defined as a history of at least one of the following: Dyspnea that qualifies at New York Heart Association (NYHA) class II or greater Angina pectoris Cardiac syncope The Heart Team agrees that the patient is low-risk, quantified by an estimated risk of death ≤3% by the calculated STS score for operative mortality at 30 days; AND agrees that SAVR would be an appropriate therapy if offered A surgeon who is experienced in Surgical Aortic Valve Replacement (SAVR) has spoken with the patient in person and stipulates that the patient understands his/her alternatives for FDA approved therapy, including open heart surgery to replace their aortic valve The institutional Heart Team determines that transfemoral TAVR is appropriate Aortic valve anatomy and dimensions suitable for TAVR using a commercially available valve Iliofemoral artery anatomy and dimensions suitable for transfemoral TAVR using a commercially available valve and delivery system Procedure status is elective Expected survival is at least 24 months Exclusion Criteria: Subject unable or unwilling to give informed consent Concomitant disease of another heart valve or the aorta that requires either transcatheter or surgical intervention Any condition that is considered a contraindication for placement of a bioprosthetic aortic valve (e.g. patient requires a mechanical aortic valve) Aortic stenosis secondary to a bicuspid aortic valve Prior bioprosthetic surgical aortic valve replacement Mechanical heart valve in another position End-stage renal disease requiring hemodialysis or peritoneal dialysis, or a creatinine clearance <20 cc/min Left ventricular ejection fraction <20% Recent (<6 months) history of stroke Symptomatic carotid or vertebral artery disease, or recent (<6 weeks) surgical or endovascular treatment of carotid stenosis Any contraindication to oral antiplatelet or anticoagulation therapy following the procedure, including recent or ongoing bleeding, or HASBLED score >3 (Table 2 - HASBLED scoring system) Severe coronary artery disease that is unrevascularized Recent (<30 days) acute myocardial infarction Patient cannot undergo transfemoral TAVR for anatomic reasons (as determined by supplemental imaging studies); this would include inadequate size of iliofemoral access vessels or an aortic annulus size that is not accommodated by the commercially available valves Any comorbidity not captured by the STS score that would make SAVR high risk, as determined by a cardiothoracic surgeon who is a member of the heart team; this includes: Porcelain or severely atherosclerotic aorta Frailty Hostile chest Internal mammary artery or other conduit either crosses midline of sternum or is adherent to sternum Severe pulmonary hypertension (PA systolic pressure > 2/3 of systemic pressure) Severe right ventricular dysfunction Ongoing sepsis or infective endocarditis Severe chronic obstructive pulmonary disease, as demonstrated by forced expiratory volume (FEV1) <750 cc Liver failure with Childs class C or D Pre-procedure shock, inotropes, mechanical assist device, or cardiac arrest Pregnancy or intent to become pregnant prior to completion of all protocol follow-up procedures Known allergy to warfarin or aspirin
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Warfarin plus Aspirin<br>100 subjects will be randomized electronically through the Electronic Data Capture System in a 1:1 fashion to warfarin plus low dose aspirin for 30-45 days | Device: TAVR<br>* Transcatheter Aortic Valve Replacement<br>Other: Warfarin plus Aspirin<br>* Subjects randomized to this arm will receive Warfarin plus aspirin for 30- 45 days post TAVR<br>|
| Other: Aspirin Monotherapy<br>100 subjects will be randomized electronically through the Electronic Data Capture System in a 1:1 fashion to low dose aspirin monotherapy for 30-45 days | Device: TAVR<br>* Transcatheter Aortic Valve Replacement<br>Other: Aspirin Only<br>* Subjects randomized to this arm will receive aspirin only post TAVR<br>|
| Other: Registry Arm<br>Upto an additional 100 subjects with preexisting indication for anti coagulation (e.g. atrial fibrillation, deep venous thrombosis, pulmonary embolism) or who are not eligible for randomization after TAVR due to development of a new indication for anti coagulation will be enrolled in the registry arm of the study. | Device: TAVR<br>* Transcatheter Aortic Valve Replacement<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All Cause Mortality |  | 30 days | 
| All Stroke | disabling and non-disabling, ischemic, hemorrhagic | 30 days | 
| Life-threatening and Major Bleeding |  | 30 days | 
| Major Vascular Complications |  | 30 Days | 
| Hospitalizations for valve-related symptoms or worsening congestive heart failure |  | 30 days | 
| Hypoattenuated leaflet thickening (HALT) |  | 30 days | 
| At least moderately restricted leaflet motion (RELM) |  | 30 days | 
| Hemodynamic dysfunction | (mean aortic valve gradient ≥20 mm Hg, AND/OR EOA ≤1.0 cm2 AND/OR DVI<0. 35, AND/OR moderate or severe prosthetic valve regurgitation) | 30 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VARC-2 device success: | Absence of procedural mortality AND Correct positioning of a single prosthetic heart valve into the proper anatomical location AND Intended performance of the prosthetic heart valve (no prosthesis-patient mismatch and mean aortic valve gradient<20 mm Hg or peak velocity<3 m/s, AND no moderate or severe prosthetic valve regurgitation) | 1 year | 
| All-cause mortality |  | 1 year | 
| All stroke | (disabling and non-disabling, ischemic and hemorrhagic) | 1 year | 
| Life-threatening and major bleeding |  | 1 year | 
| Major vascular complications |  | 1 year | 
| Hospitalizations for valve-related symptoms or worsening congestive heart failure |  | 1 year | 
| Acute kidney injury |  | 1 year | 
| Pacemaker implantation |  | 1 year | 
| Endocarditis |  | 1 year |