Heterotopic Implantation Of the Edwards-Sapien Transcatheter Aortic Valve in the Inferior VEna Cava for the Treatment of Severe Tricuspid Regurgitation (HOVER)

Study Overview
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Brief Summary
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The goal of this study is to determine the short term safety (<30 days) and efficacy (6 months) of the heterotopic implantation of the Edwards-Sapien XT valve in the inferior vena cava for the treatment of severe tricuspid regurgitation in patients who are inoperable or at a very high surgical risk for tricuspid valve replacement.

Detailed Description
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This is a prospective multi-center, non-blinded (open label), non-randomized safety and feasibility study of the heterotopic implantation of the Edwards-Sapien XT or S3 valve in the inferior vena cava for the treatment of severe tricuspid regurgitation in patients who are inoperable or at a very high surgical risk for tricuspid valve replacement.

Official Title
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Heterotopic Implantation Of the Edwards-Sapien Transcatheter Aortic Valve in the Inferior VEna Cava for the Treatment of Severe Tricuspid Regurgitation HOVER Trial

Conditions
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Tricuspid Regurgitation

Intervention / Treatment
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* Device: Heterotopic Implantation Of the Edwards-Sapien XT Transcatheter Valve in the Inferior VEna Cava


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be at least 21 years old. The patient must have severe, symptomatic (ACC/AHA Stage D symptoms) tricuspid regurgitation (TR) as assessed by 2D echocardiogram with evidence of peripheral and central venous congestion (specifically lower extremity edema and abdominal ascites requiring diuretics.) The patient must be evaluated by a heart team of physicians including an interventional cardiologist, cardiothoracic surgeon, heart failure specialist, and imaging specialist, and presented for review at a local multi-disciplinary conference. By consensus, the heart team must agree (and verify in the case review process) that valve implantation will likely benefit the patient. The heart team must agree that medical factors preclude operation, based on a conclusion that the probability of death or serious, irreversible morbidity exceeds the probability of meaningful improvement. Also, other factors which may increase the patients perceived surgical risk for inclusion in the trial will be clearly delineated if they are present. These include, but are not limited to the following as defined by VARC 2: Frailty, Hostile chest, porcelain aorta, IMA or other critical conduit crossing the midline or adherent to the posterior table of sternum, severe right ventricular (RV) dysfunction. The surgeons' consultation notes shall specify the medical or anatomic factors leading to that conclusion. At least one of the cardiac surgeon assessors must have interviewed and examined the patient. The study patient provides informed consent and agrees to comply with all required post-procedure follow-up visits, including annual visits up to 5 years. Exclusion Criteria: Heart Team assessment of operability (the heart team considers the patient to be a good surgical candidate). Evidence of an acute myocardial infarction ≤ 1 month (30 days) before the intended treatment [defined as: Q wave MI, or non-Q wave MI with total CK elevation of CK-MB ≥ twice normal in the presence of MB elevation and/or troponin level elevation (WHO definition)]. Untreated, severe, left sided valvular heart disease including mitral regurgitation or stenosis, and aortic regurgitation or stenosis. Mean pulmonary artery pressures ≥40mmHG and PVR >4 woods units as assessed by right heart catheterization. Any therapeutic invasive cardiac procedure resulting in a permanent implant that is performed within 30 days of the index procedure. Examples of permanent implant would include any new heart valve. Implantation of a permanent pacemaker is excluded. Patients with planned concomitant surgical or transcatheter ablation for Atrial Fibrillation. Leukopenia (WBC < 3000 cell/mL), acute anemia (Hgb < 9 g/dL), Thrombocytopenia (Plt < 50,000 cell/mL). Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or mechanical heart assistance within 30 days of screening evaluation. Need for emergency surgery for any reason. Left ventricular ejection fraction <40%. Echocardiographic evidence of intracardiac mass, thrombus or vegetation. Active upper GI bleeding within 3 months (90 days) prior to procedure. A known contraindication or hypersensitivity to all anticoagulation regimens, or inability to be anticoagulated for the study procedure. Recent CVA clinically confirmed (by neurologist) or neuroimaging confirmed stroke or transient ischemic attack (TIA) within 6 months (180 days) of the procedure. Estimated life expectancy < 1 year from conditions other than TR. Expectation that patient will not improve despite treatment of tricuspid regurgitation Currently participating in another investigational cardiac device study or any other clinical trial, including drugs or biologics. Note: Trials requiring extended follow-up for products that were investigational, but have since become commercially available, are not considered investigational trials. Active bacterial endocarditis within 6 months (180 days) of procedure. Patients with signs or symptoms of SVC syndrome, or hepatic cirrhosis not felt due to passive congestion from TR. 20: Subject unable to personally provide informed consent 21. FEV1<30% of predicted 22. Model for End State Liver Disease (MELD) score ≥21 (calculated per reference study.

Ages Eligible for Study
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Minimum Age: 22 Years

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Severe Tricuspid Regurgitation<br>This is a non-blinded (open label), non-randomized safety and feasibility study of the heterotopic implantation of the Edwards Sapien 3 valve. | Device: Heterotopic Implantation Of the Edwards-Sapien XT Transcatheter Valve in the Inferior VEna Cava<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Procedural success | Procedural success will include both device success and no device/procedure related SAE's including: all death, all stroke, MI, new AKI grade 3, life threatening bleeding, major vascular complications (arterial or venous-requiring unplanned intervention), pericardial effusion or tamponade requiring drainage, SVC syndrome | 30 days | 
| Individual patient success | Individual patient success is defined by device success and the following: no re-hospitalizations for right sided heart failure or right sided heart failure equivalents including drainage of ascites or pleural effusions, new listing for heart transplant, VAD, or other mechanical support; improvement in one of three variables: KCCQ improvement>15 vs. baseline; 6MWT improvement> 70 meters vs. baseline; or VO2 peak improvement > 6% vs baseline.. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LE edema | Improvement in LE edema measured by the Villalta Scale | 30 days, 6 months, annually to 5 years | 
| Stroke and TIA | Occurrence of stroke or TIA by Valve Academic Research Consortium (VARC-2) criteria | 30 days, 6 months, annually to 5 years | 
| Mortality | Death | 30 days, 6 months, annually to 5 years | 
| Myocardial Infarction | Occurrence of MI by VARC-2 | 30 days, 6 months, annually to 5 years | 
| Acute kidney injury | Occurrence of acute kidney injury by VARC-2 | 30 days, 6 months, annually to 5 years | 
| Major vascular complications | Occurrence of major vascular complications by VARC-2 | 30 days, 6 months, annually to 5 years | 
| EORTC QLQ-C30 | Improvement in Quality of Life questionnaire | 30 days, 6 months, annually to 5 years | 
| ESAS-AM | Improvement in Quality of Life questionnaire | 30 days, 6 months, annually to 5 years |