The primary objective of this study is to compare in a non-inferiority design the safety and efficacy of iwFR (or comparable resting diastolic indices)-guided complete revascularization after (within 1-45 days) with iwFR (or comparable resting…
ID
Source
Brief title
Condition
- Other condition
- Cardiac valve disorders
Synonym
Health condition
cardiac disorders --> coronary artery disorders
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Major adverse cardiovascular events (MACE) at 1 year, defined as a composite
of:
• All-cause death
• Non-fatal myocardial infarction (MI)
• Ischemia-driven revascularization
• Rehospitalization (valve- or procedure-related including heart failure)
• Life-threatening/disabling or major bleeding (according to VARC-2 (5))
Secondary outcome
Secondary endpoints will be assessed at hospital discharge (first and second
hospitalization), 3 months, 1 year, 2 years, and 5 years, and comprise:
• Primary composite endpoint at hospital discharge (first and second
hospitalization), at 3 months, 2 years, and 5 years
• Single components of the primary endpoint
• All-cause death and MI
• All-cause death, MI, and ischemia driven revascularization
• All-cause death, MI, ischemia driven revascularization, and rehospitalization
• Cardiovascular death
• Cardiovascular death and MI
• Stroke
• Peri-procedural MI (PCI)
• Peri-procedural MI (TAVI)
• Major vascular complications (according to VARC-2 (5))
• Bleeding events (Bleeding Academic Research Consortium [BARC] definition)
• Symptom status and change from baseline in symptom status (Canadian
Cardiovascular Society [CCS] and New York Heart Association [NYHA]
classification)
The following secondary endpoint will be assessed at hospital admission for the
second procedure, 3 months, 1 year, 2 years, and 5
years:
• Quality of Life (QoL) as assessed by the Kansas City Cardiomyopathy
questionnaire (KCCQ) and the Toronto Aortic Stenosis Quality of Life
questionnaire (TASQ)
• Change from baseline in QoL as assessed by the KCCQ and the TASQ
Background summary
Optimal timing of coronary revascularization in patients with severe aortic
stenosis and concomitant coronary artery disease undergoing transcatheter
aortic valve implantation (TAVI) is unknown.
Recent studies have provided a large body of evidence supporting complete
coronary revascularization in hemodynamically stable patients presenting with
acute coronary syndromes and multivessel disease in comparison to culprit
lesion only percutaneous coronary intervention (PCI) and optimal medical
therapy for non-culprit lesions. (1-4) Accordingly, it can be assumed that
coronary revascularization for coronary artery lesions in patients undergoing
TAVI is superior to optimal medical therapy alone. In clinical routine, PCI
performed before TAVI represents the standard approach which is supported by
observational evidence. Optimal timing of PCI in patients undergoing TAVI has
not been investigated, yet. Percutaneous coronary intervention after TAVI may
entail the advantage of a lower risk of vascular and bleeding complications and
avoid aortic stenosis-related alterations of coronary physiology.
Study objective
The primary objective of this study is to compare in a non-inferiority design
the safety and efficacy of iwFR (or comparable resting diastolic
indices)-guided complete revascularization after (within 1-45 days) with iwFR
(or comparable resting diastolic indices)-guided complete revascularization
before (within 1-45 days) TAVI using the Edwards SAPIEN Transcatheter Heart
Valve* in patients with severe aortic stenosis and concomitant coronary artery
disease accepted for TAVI and PCI by the multidisciplinary Heart Team.
We hypothesize that iwFR (or comparable resting diastolic indices)-guided
complete revascularization after TAVI is non-inferior to iwFR (or comparable
resting diastolic indices)-guided complete revascularization before TAVI, when
using the Edwards SAPIEN Transcatheter Heart Valve*. Non-inferiority of iwFR
(or comparable resting diastolic indices)-guided complete revascularization
performed after TAVI would provide flexibility in procedural planning, allow
for early symptom relief of patients with severe aortic stenosis, and define
the transcatheter heart valve design suited best for patients with severe
aortic stenosis and concomitant coronary artery disease. Further, coronary
revascularization after TAVI may contain a lower risk of vascular and bleeding
complications, given the need for dual antiplatelet therapy after PCI, and
potentially avoid aortic stenosis-related alterations in coronary physiology.
Study design
TAVI PCI is an investigator-initiated, randomized, multi-center, two-arm,
open-label, non-inferiority trial. Patients with severe aortic stenosis and
concomitant coronary artery disease will be randomized in a 1:1 ratio to
instantaneous wave-free ratio (iwFR)-guided complete coronary revascularization
1) before (within 1-45 days) TAVI (Group 1), or
2) after (within 1-45 days) TAVI (Group 2)
Intervention
TAVI & PCI are the same for patients participating in the trial as for all
other patients not participating, as only the sequence of procedures is
investigated in the study.
TRANSCATHETER AORTIC VALVE IMPLANTATION (TAVI)
Interventional cardiologists selected to participate as Investigators in this
study are qualified and board certified. All clinicians have broad experience
with the procedures. Transcatheter aortic valve implantation is performed
according to current guidelines and recommendations using the he commercially
available balloon-expandable Edwards SAPIEN Transcatheter Heart Valve* (see
8.1.1).(6) The choice of prosthesis size is left at the discretion of the
operator. The Edwards SAPIEN Transcatheter Heart Valve*, the associated
delivery system, and all components will be used according to the respective
Instructions for Use (IFU). During the procedure, at least 5000 IU or 70 - 100
IU/kg unfractionated heparin to maintain an ACT >250 seconds is required. After
TAVI, antiplatelet therapy with aspirin is given. Patients with any indication
for oral anticoagulation are treated with oral anticoagulation alone.
Edwards SAPIEN Transcatheter Heart Valve*
The Edwards SAPIEN Transcatheter Heart Valve* respective Instructions for Use
(IFU) have to be followed and filed in the investigator site file.
The manufacturer is Edwards Lifesciences LLC, One Edwards Way, lrvine, CA
92614, United States Of America.
PERCUTANEOUS CORONARY INTERVENTION (PCI)
Interventional cardiologists selected to participate as Investigators in this
study are qualified and board certified and have broad experience with the
procedures. Coronary revascularization is performed according to current
guidelines and recommendations using CE certified devices.(30) Coronary
revascularization should be attempted in all coronary artery lesions with
40-90% diameter stenosis and iwFR (or a comparable resting diastolic index)
<=0.89 or with >90% diameter stenosis on coronary angiogram (by visual
estimation) in a coronary artery >=2.5 mm in diameter. While measurement of iwFR
(or resting full-cycle ratio [RFR], diastolic hyperemia-free ratio [DFR], or a
comparable resting diastolic index) is mandatory for the assessment of coronary
artery lesions with 40-90% diameter stenosis, investigators are asked to also
perform other resting and hyperemic indices such as resting distal to aortic
coronary pressure ratio (Pd/Pa), fractional flow reserve (FFR), quantitative
flow ratio (QFR), coronary flow reserve (CFR), or index of microcirculatory
resistance (IMR). Quantiative flow ratio analysis will be performed offline at
the Andreas Grüntzig Coronary Angiography and Physiology Core Lab for all
patients. Complete revascularisation is desirable, but the extent of
revascularisation is left to the discretion of the operator performing PCI. All
lesions identified as amenable to PCI at randomisation should undergo coronary
revascularization. The access site (radial or femoral), the use of
intravascular imaging modalities (optical coherence tomography, intravascular
ultrasound), and the use of PCI equipment (drug-eluting stent, drug-coated
balloon, rotablation, etc.) are left at the discretion of the operator. In
general, PCI of chronic total occlusions (CTO) that are well collateralized
should only be attempted if, in the opinion of an experienced CTO operator,
there is a high likelihood of PCI success.
All patients must be pre-treated with aspirin. During the procedure, at least
5*000 IU or 70 - 100 IU/kg unfractionated heparin to maintain an activated
clotting time (ACT) >250 seconds is required. Following PCI with stent
implantation, dual antiplatelet therapy (DAPT) with aspirin and the P2Y12
inhibitor clopidogrel should be given according to current guidelines and for
at least 3 months, preferably 6 months.(31) In patients not already
pre-treated with aspirin or clopidogrel, an initial dose of aspirin of 250-500
mg i. v. and a loading dose of clopidogrel of 300-600 mg orally should be given
peri-procedurally.
Patients with any indication for oral anticoagulation are treated with triple
therapy for 1 to 4 weeks, followed by dual therapy (oral anticoagulation and
clopidogrel) for at least 3 months and up to 12 months, based on their
individual bleeding and ischemic risks and according to current guideline
recommendations.(31, 32)
Study burden and risks
The risks and benefits of the procedures, PCI and TAVI, are the same for
patients participating in the trial as for all other patients not
participating, as only the sequence of procedures is investigated in the study.
PCI prior to TAVI (Group 1)
Percutaneous coronary intervention before TAVI may be related with a reduced
ischemic burden during valve implantation and rapid pacing, but may have an
increased bleeding risk when dual antiplatelet therapy is administered after
PCI. In two meta-analyses (see 4.1 BACKGROUND AND RATIONALE), revascularization
before TAVI conferred no clinical advantage with respect to clinical
outcomes,(28, 29) but was related with an increased risk of major vascular
complications and mortality.(28) In line with these findings, PCI shortly
before TAVI was associated with an increased risk of minor bleeding and
vascular injury as compared with remote staged PCI in a retrospective cohort
study.(26) These studies, however, are limited by their rather small sample
size and their observational, retrospective design.
PCI after TAVI (Group 2)
Percutaneous coronary intervention after TAVI may entail the advantage of a
lower risk of vascular and bleeding complications and avoid aortic
stenosis-related alterations of coronary physiology, but may be related with an
increased ischemic risk during valve implantation and rapid pacing
Raemistrasse 100
Zürich 8091
CH
Raemistrasse 100
Zürich 8091
CH
Listed location countries
Age
Inclusion criteria
• Patients >=18 years with severe aortic stenosis and concomitant coronary
artery disease accepted for transfemoral TAVI with an Edwards SAPIEN
Transcatheter Heart Valve* by transfemoral access and PCI by the
multidisciplinary Heart Team
• 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:
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(6)
• At least one coronary artery lesion with 40-90% diameter stenosis and iwFR
<=0.89 or with >90% 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
• Written informed consent
Exclusion criteria
• TAVI by transapical, subclavian, or transaortic access
• Admission with acute myocardial infarction within 30 days before randomization
• Elective coronary revascularization within 3 months before randomization
• Previous coronary artery bypass grafting (CABG)
• Syntax Score I >=33
• Any contraindications for dual antiplatelet therapy with aspirin and a P2Y12
inhibitor (clopidogrel, ticagrelor or prasugrel), except for patients on oral
anticoagulation
• Planned open heart surgery
• Known pregnancy at the time of inclusion
• Life expectancy <1 year due to other severe non-cardiac disease
• Participation in another clinical study with an investigational product
• Acute COVID-19 infection
• Patient with previously treated aortic stenosis
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT04310046 |
| CCMO | NL76284.078.21 |