Optimal Timing of Transcatheter Aortic Valve Implantation and Percutaneous Coronary Intervention - The TAVI PCI Trial (TAVI-PCI)

The primary objective of this study is to compare, in patients with severe aortic stenosis and concomitant coronary artery disease accepted for transcatheter aortic valve implantation (TAVI) and percutaneous coronary intervention (PCI) by the multidisciplinary Heart Team, the safety and efficacy of angiography-guided complete revascularization performed after (within 1-45 days) with angiography-guided complete revascularization performed before (within 1-45 days) TAVI using the Edwards SAPIEN Transcatheter Heart Valve®.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease; Aortic Stenosis; PCI; TAVI
• Intervention / Treatment: Procedure: PCI before TAVI; Procedure: PCI after TAVI

Detailed Description

The prevalence of coronary artery disease in patients with severe aortic stenosis is high. About 30-60% of patients undergoing TAVI exhibit coexisting coronary artery disease. Optimal timing of coronary revascularization in patients with severe aortic stenosis and concomitant coronary artery disease undergoing TAVI is uncertain.

The goal of this investigator-initiated, randomized, multicenter, two-arm, open-label, non-inferiority trial is to compare two treatment strategies that are currently performed in clinical practice: PCI before TAVI versus PCI after TAVI in patients with severe aortic stenosis and concomitant coronary artery disease.

In this trial, patients with severe aortic stenosis and concomitant coronary artery disease accepted for TAVI and PCI by the Heart Team will be randomized in a 1:1 ratio to the following strategies: angiography-guided complete coronary revascularization before (within 1-45 days) or after (within 1-45 days) TAVI using the Edwards SAPIEN Transcatheter Heart Valve®.

For both treatment groups, coronary artery lesions with ≥70% diameter stenosis on coronary angiogram (by visual estimation) in a coronary artery ≥2.5 mm in diameter are considered significant.

TAVI and PCI will be performed according to current guidelines.

• Study Type: Interventional
• Enrollment (Estimated): 986
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Barbara E. Stähli, MD, eMBA; Phone Number: +41 44 255 11 11; Email: Barbara.Staehli@usz.ch
• Study Contact Backup: Name: Markus Kasel, MD; Email: markus.kasel@usz.ch

Study Locations

• Switzerland
  • Zürich, Switzerland, 8091
    • Recruiting
    • University Hospital Zürich, Cardiology Department
    • Contact: Barbara E. Stähli, MD, eMBA; Email: barbara.staehli@usz.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients ≥18 years with severe aortic stenosis and concomitant coronary artery disease accepted for transfemoral TAVI with an Edwards SAPIEN Transcatheter Heart Valve™ and PCI by a multidisciplinary Heart Team.

2. Severe aortic stenosis defined as aortic valve area (AVA) ≤1.0 cm2 and/or mean pressure gradient ≥40 mmHg (echocardiography) and at least one of the following criteria:

   1. Dyspnea
   2. Angina symptoms
   3. Syncope
   4. Decline in left ventricular ejection fraction <50%, symptoms or fall in blood pressure on exercise testing, or presence of high-risk criteria (peak transaortic velocity >5.5 m/s, severe valve calcification, peak transaortic velocity progression ≥0.3 m/s per year, or severe pulmonary hypertension with systolic pulmonary artery pressure >60 mmHg) according to current guidelines.
3. At least one coronary artery lesion with ≥70% diameter stenosis on coronary angiogram (by visual estimation) in a coronary artery ≥2.5 mm in diameter and Thrombolysis in Myocardial Infarction (TIMI) flow grade III, deemed amenable to PCI within 45 days before or after TAVI. Hemodynamic lesion assessment by fractional flow reserve (FFR), instantaneous wave-free ratio (iwFR), or comparable indices as well as intravascular imaging-guided PCI are left at the discretion of the operator.
4. Written informed consent.

Exclusion Criteria:

1. TAVI by transapical, subclavian, or transaortic access
2. Admission with acute myocardial infarction within 30 days before randomization
3. Elective coronary revascularization within 3 months before randomization
4. Previous coronary artery bypass grafting (CABG)
5. Syntax Score I ≥33
6. Any contraindications for dual antiplatelet therapy with aspirin and a P2Y12 inhibitor (clopidogrel, ticagrelor or prasugrel), except for patients on oral anticoagulation
7. Planned open heart surgery
8. Known pregnancy at the time of inclusion
9. Life expectancy <1 year due to other severe non-cardiac disease
10. Participation in another clinical study with an investigational product
11. Acute COVID-19 infection
12. Patient with previously treated aortic stenosis

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: PCI before TAVI; PCI is performed within 1-45 days before TAVI.	Procedure: PCI before TAVI; TAVI is performed using the Edwards SAPIEN Transcatheter Heart Valve®. PCI is performed in any suitable lesion with ≥70% diameter stenosis on coronary angiography in a coronary artery ≥2.5 mm in diameter.
Experimental: PCI after TAVI; PCI is performed within 1-45 days after TAVI.	Procedure: PCI after TAVI; TAVI is performed using the Edwards SAPIEN Transcatheter Heart Valve®. PCI is performed in any suitable lesion with ≥70% diameter stenosis on coronary angiography in a coronary artery ≥2.5 mm in diameter.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary outcome measure is the number of participants experiencing the primary outcome measure	The primary outcome measure is a composite of: All-cause death; Non-fatal myocardial infarction; Ischemia-driven revascularization; Rehospitalization (valve- or procedure-related including heart failure); Life-threatening/disabling or major bleeding (according to VARC-2)	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary outcome measure		Discharge (hospitalization first and second procedure), 3 months, 2 years and 5 years
Single components of the primary endpoint		Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
All cause death and myocardial infarction		Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
Cardiovascular death and myocardial infarction		Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
All cause death, myocardial infarction and ischemia-driven revascularization		Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
All cause death, myocardial infarction, ischemia-driven revascularization and rehospitalization		Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
Cardiovascular death		Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
Stroke		Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
Peri-procedural myocardial infarction (PCI)		Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
Peri-procedural myocardial infarction (TAVI)		Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
Major vascular complications		Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
Bleeding events	Bleeding events are defined according to the Bleeding Academic Research Consortium (BARC) definition	Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
Symptom status and change from baseline in symptom status (Canadian Cardiovascular Society (CCS) and New York Hear Association (NYHA) classification)		Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
Quality of life (as assessed by the KCCQ and TASQ questionnaires)	Kansas City Cardiomyopathy questionnaire (KCCQ) and the Toronto Aortic Stenosis Quality of Life questionnaire (TASQ)	Admission (for second procedure), 3 months, 1 year, 2 years and 5 years
Change from baseline in Quality of life (as assessed by the KCCQ and TASQ questionnaires)	Kansas City Cardiomyopathy questionnaire (KCCQ) and the Toronto Aortic Stenosis Quality of Life questionnaire (TASQ)	Admission (for second procedure), 3 months, 1 year, 2 years and 5 years

Other Outcome Measures

Outcome Measure	Time Frame
Procedural success (PCI)	Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
Device success (TAVI)	Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
Any revascularization	Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
Target lesion revascularization	Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
Target vessel revascularization	Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
In-stent thrombosis	Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
Acute kidney injury	Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
New-onset atrial fibrillation	Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
New permanent pacemaker implantation	Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
Aortic valve-related dysfunction requiring repeat procedure	Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
Amount of contrast medium (PCI)	Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
Fluoroscopy time (PCI)	Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
Radiation exposure (dose area product, PCI)	Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
Conversion to open heart surgery	Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years
Use of catecholamines during PCI	Discharge (hospitalization first and second procedure), 3 months, 1 year, 2 years and 5 years

Collaborators and Investigators

• Sponsor: University of Zurich
• Investigators: Principal Investigator: Markus Kasel, MD, University Hospital, Zürich; Principal Investigator: Barbara E. Stähli, MD, eMBA, University Hospital, Zürich

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2020
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2031

Study Registration Dates

• First Submitted: February 12, 2020
• First Submitted That Met QC Criteria: March 12, 2020
• First Posted (Actual): March 17, 2020

Study Record Updates

• Last Update Posted (Estimated): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Vascular Diseases; Cardiovascular Diseases; Coronary Artery Disease; Percutaneous Coronary Intervention; Aortic Stenosis; Transcatheter Aortic Valve Replacement; Arteriosclerosis; Heart Diseases; Myocardial Ischemia; Arterial Occlusive Diseases; Valvular Disease
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Aortic Valve Stenosis
• Other Study ID Numbers: TAVI PCI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No