Clinical trial NCT04144881: Angiographic Control Vs. Ischemia-driven Management of Patients Treated with PCI on Left Main with Drug-eluting Stents
Official title: Angiographic Control Vs. Ischemia-driven Management of Patients Undergoing Percutaneous Revascularization of the Unprotected Left Main Coronary Artery with Second-generation Drug Eluting Stents: the PULSE Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Coronary Syndrome
Stable Chronic Angina
Coronary Artery Disease
Left Main Coronary Artery Disease
Lead sponsor: A.O.U. Città della Salute e della Scienza
Sponsor class: OTHER
Collaborators: name: Università degli Studi di Ferrara
name: Ospedale San Luigi Gonzaga, Orbassano
name: Ospedale Santa Croce-Carle Cuneo
name: Azienda USL Reggio Emilia - IRCCS
name: AUSL Romagna Rimini
name: University of Ferrara Department of Life Sciences and Biotechnology
First posted: 2019-10-30
Enrollment: 606
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The present study aims to compare a planned angiographic control (PAC) follow-up strategy vs. conservative management for patients treated with drug-eluting stents on unprotected left main artery in a prospective, randomized setting. PAC will be performed by coronary computed tomography (CCT), to avoid the limitations of the invasive coronary angiography which is usually employed to perform PAC. The superiority of a PAC-based approach will be tested on a hard clinical end-point such as the incidence of major adverse cardiovascular events. The investigators will also assess the performance of CCT as a tool to perform PAC.

Detailed description: Given the undefined picture surrounding the appropriateness of planned angiographic control (PAC) following percutaneous coronary intervention (PCI) of the unprotected left main (ULM) with drug-eluting stents (DES), our aim is to evaluate, in a prospective, randomized, setting, the potential benefits of a PAC-based strategy vs. ischemia and symptoms driven conservative management. The disease of the native ULM is associated with an unfavorable prognostic outcome, which can be at least partially reversed by revascularization. Significant stenosis of the stented ULM caused by in-stent restenosis (ISR), however, presents some peculiar pathophysiological, flow-related and shear-stress features, which partly makes it a distinct disease as compared to native vessel atherosclerosis. Treatment of ISR, moreover, is a scarcely standardized and often complex procedure; some uncertainties still persist regarding the best strategy to treat ISR (stent-in-stent, drug-eluting balloons, dilation with conventional balloons). Computed coronary tomography (CCT) can precisely and not-invasively assess the presence of ISR in the stented ULM, without exposing the patients to the risks of invasive catheterization. CCT may provide an accurate reconstruction of the stented vessels, exposing the patients to a limited amount of contrast dye (approximately, 80-100 cc) and of radiation dose (approximately, 92 mGy). CCT has a very high negative predictive value for ISR, thus limiting the negative impact of the indiscriminate execution of invasive angiography on all patients treated by PCI of the ULM. Only patients with relevant ISR of ULM at CCT will undergo coronary angiography to confirm the presence of critical stenosis, and fractional flow reserve (FFR) and/or intravascular ultrasound (IVUS) will be performed in dubious cases.

An increased rate of PCI has to be taken in to account with a PAC-based approach. However, with the accurate, stepwise selection of the patients and the lesions amenable to PCI of our study protocol, based on CCT, coronary angiography and, where necessary, FFR/IVUS, the increased rate of PCI is not expected to bear a negative prognostic impact. Based on these premises, our hypothesis is that early, appropriate, detection of ULM ISR and its subsequent treatment may positively impact patients' survival and reduce the incidence of adverse cardiovascular events.

Specific aim 1:

Evaluation of the effectiveness and safety of a PAC-based approach to follow-up patients treated by PCI of the ULM with DES-II

Specific aim 2:

Assessment of the incidence of ISR in patients undergoing PCI of the ULM with DES-II and evaluation of the diagnostic accuracy of CCT in the evaluation of ISR in the stented ULM

Specific Aim 3:

Assessment of the prognostic implications and safety of the PCI of ISR of the ULM detected by PAC as compared to conservative management with revascularization driven by symptoms and ischemia.

For this purpose in this prospective, randomized controlled trial (RCT), patients will be enrolled following the index percutaneous revascularization of ULM with DES. Patients will be randomized in a 1:1 fashion to PAC-based management with CCT vs.

symptoms and ischemia driven conservative management.

Eligibility criteria: Inclusion Criteria:

Patients with ULM disease treated by PCI with DES-II with the following inclusion criteria:

* Age 18-85.
* Glomerular filtration rate \> 30 ml/min Indication to percutaneous revascularization of ULM according to Syntax score (\< 33) or, in dubious cases, after Heart Team evaluation

Exclusion Criteria:

* Cardiogenic shock
* Refusal or inability to provide informed consent

Primary outcomes:
measure: Major adverse cardiovascular events (MACE)
timeFrame: 18 months after the index revascularization
Secondary outcomes:
measure: Target lesion revascularization (TLR)
timeFrame: 18 months after the index revascularization
measure: All cause death
timeFrame: within 18 months from the index revascularization
measure: stent thrombosis
timeFrame: within 18 months from the index revascularization
measure: CV death
timeFrame: within 18 months from the index revascularization
measure: Myocardial infarction
timeFrame: within 18 months from the index revascularization
Other outcomes:
measure: AKI
timeFrame: 2 days after CCT in the experimental arm
measure: Renal function impairment
timeFrame: 18 months after the index revascularization
measure: Overall bleedings
timeFrame: 18 months after the index revascularization
measure: Major bleedings
timeFrame: 18 months after the index revascularization
measure: procedural complications
timeFrame: Index hospitalization
Locations:
city: Ferrara
country: Italy
facility: Azienda Ospedaliero-Universitaria di Ferrara
city: Orbassano
country: Italy
facility: Ospedale San Luigi Gonzaga, Orbassano
city: Torino
country: Italy
facility: AOU Città della Salute e della Scienza di Torino
Study officials:
affiliation: A.O.U. Città della Salute e della Scienza
name: Fabrizio D'Ascenzo, MD
role: PRINCIPAL_INVESTIGATOR
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