The TransCatheter Valve and Vessels Trial

Study Overview
=================
Brief Summary
-----------------
The trial objective is to investigate whether Fractional Flow Reserve (FFR)-Guided Percutaneous Coronary Intervention (PCI) and TransCatheter Aortic Valve Implantation (TAVI) strategy for treatment of multivessel disease and aortic stenosis will be non-inferior to Coronary Artery By-pass Grafting (CABG) and Surgical Aortic Valve Replacement (SAVR) for a composite primary endpoint of all-cause mortality, stroke, myocardial infarction, coronary or valve re-intervention and life-threatening or disabling bleeding at one year.

Detailed Description
-----------------
Prospective, randomized, controlled, open label, multicenter, international, non-inferiority trial If the Heart Team decides that a coronary revascularization and aortic valve replacement is needed and the patient complies with inclusion and exclusion criteria then the patient will be randomized in a 1:1 fashion between FFR-guided PCI + TAVI and CABG + SAVR. Patients will receive optimal medical treatment at discharge. Follow-up will be performed at 30 days and at one year. During the 30 day follow-up visit (after TAVI) patients will be evaluated for symptoms of angina.

Official Title
-----------------
TransCatheter Aortic Valve Implantation and Fractional Flow Reserve-Guided Percutaneous Coronary Intervention Versus Conventional Surgical Aortic Valve Replacement and Coronary By-Pass Grafts for Treatment of Patients With Coronary MultiVessel Disease and Aortic Valve Stenosis

Conditions
-----------------
TAVI, Aortic Stenosis, Multi Vessel Coronary Artery Disease, CABG, PCI, Fractional Flow Reserve

Intervention / Treatment
-----------------
* Device: FFR-guided PCI and TAVI
* Device: CABG and SAVR


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Symptomatic patients aged ≥70 years with aortic stenosis fulfilling one of these criteria (Aortic Valve Area (AVA) ≤1 cm2; mean gradient ≥40 mmHg; Aortic jet velocity >4 m/sec; or Velocity index ≤ 0.25) feasible for treatment by both trans femoral or subclavian approach TAVI as well as conventional SAVR and where the Heart Team decides that treatment is needed (final decision is left to the Heart Team) Presence of ≥2 de novo coronary lesions of ≥50% diameter stenosis on visual estimation located in any of main epicardial coronary arteries, or side branches of a lumen caliber of more than 2 mm or single Left Anterior Descending (LAD) lesion with more than 20 mm length or involving a bifurcation (complex), feasible for treatment with CABG as well as PCI (Heart Team decision) Patients willing and capable to provide written informed consent Exclusion Criteria: Patients in cardiogenic shock or acute heart failure, requiring inotropic agents during procedure and/or i.v. diuretics <48 hours before procedure Left ventricular ejection fraction <30% Concomitant presence of other than aortic valve disease requiring intervention Previous CABG, SAVR, TAVI or thoracotomy for any other reason Bicuspid or unicuspid aortic valve Recent myocardial infarction (less than 2 weeks) Involvement of left main trifurcation (all three branches being larger than 2 mm) Expected total stent length more 60mm per vessel FFR measurement judged impossible Life expectancy <1 year Known malignancy Contraindication for dual antiplatelet therapy or expected surgical intervention requiring interruption of Dual Antiplatelet Therapy (DAPT) in the first 6 months Reduced renal function (Glomerular Filtration Rate (GFR) <29 ml/min/1.73m2; Kidney Disease Outcomes Quality Initiative (KDOQI) stage 4 and 5) Previous disabling stroke, Transient Ischemic Attack (TIA) in the last 6 months, or known severe stenosis of carotid or vertebral arteries Participation in other investigational clinical trials

Ages Eligible for Study
-----------------
Minimum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FFR-guided PCI and TAVI<br>FFR-guided PCI and subsequently TAVI treatment with the Medtronic CoreValve Evolut R or Medtronic CoreValve Evolut R PRO | Device: FFR-guided PCI and TAVI<br>* Treatment of subjects with multivessel coronary artery disease and aortic stenosis for FFR-guided PCI and TAVI (Medtronic CoreValve Evolut R or Medtronic CoreValve Evolut R PRO)<br>|
| Active Comparator: CABG and SAVR<br>CABG and SAVR | Device: CABG and SAVR<br>* Treatment of subjects with multivessel coronary artery disease and aortic stenosis for CABG and SAVR<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint is a composite of all-cause mortality, myocardial infarction, disabling stroke, unscheduled clinically-driven target vessel revascularization, valve re-intervention, and life threatening or disabling bleeding at one year |  | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Adverse Cardiac Events (MACE: a composite of cardiovascular mortality, all stroke, myocardial infarction, unscheduled coronary or valve re-intervention) at one year |  | one year | 
| All-cause mortality and all stroke at 30 days and at one year |  | 30 days and one year | 
| Life-threatening or disabling bleeding at 30 days and one year |  | 30 days and one year | 
| Life-threatening or disabling bleeding and major bleeding at 30 days and at one year |  | 30 days and one year | 
| Rate of conduction disturbances requiring a permanent pacemaker at 30 days and at one year |  | 30 days and one year | 
| Access-related complications at 30 days |  | 30 days | 
| Acute kidney injury (Acute Kidney Injury Network (AKIN) classification) at 30 days and at one year |  | 30 days and one year | 
| Stent thrombosis according to Academic Research Consortium (ARC) criteria (definite and probable) at 30 days and at one year |  | 30 days and one year | 
| Device success (Valve Academic Research Consortium (VARC) 2 definition) |  | procedure | 
| Early Safety at 30 days (VARC 2 definition) |  | 30 days | 
| Early Efficacy at 30 days (VARC 2 definition) |  | 30 days | 
| Time Related Valve Safety at 30 days (VARC 2 definition) |  | 30 days | 
| Echocardiographic assessment of prosthetic valve performance at discharge and at one year using the following measures: a) transvalvular mean gradient, b) Effective Orifice Area (EOA), c) degree of prosthetic aortic valve regurgitation |  | discharge and at one year | 
| Clinically driven revascularisation at 30 days and at one year |  | 30 days and one year | 
| Change in New York Heart Association (NYHA) class before treatment, at 30 days and at one year |  | 30 days and one year | 
| Change in Canadian Cardiovascular Society (CCS) class before treatment, at 30 days and at one year |  | 30 days and one year | 
| Quality of life (Short Form (SF)-36) before treatment and at one year |  | one year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Aortic Stenosis (AS), Multi Vessel Coronary Artery Disease (MVD), TransCatheter Aortic Valve Implantation (TAVI), Coronary Artery By-pass Grafting (CABG), Percutaneous Coronary Intervention (PCI), Fractional Flow Reserve (FFR), Surgical Aortic Valve Replacement (SAVR)