Angiographic Control vs. Ischemia-driven Management of Patients Treated With PCI on Left Main With Drug-eluting Stents

Coronary Artery Disease Clinical Trial

— PULSE  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04144881
• Other study ID #: PULSE
• Status: Recruiting
• Phase: N/A
• Start date: October 15, 2019
• Est. completion date: October 15, 2022

Study information

• Verified date: October 2019
• Source: Azienda Ospedaliera Città della Salute e della Scienza di Torino
• Contact: Fabrizio D'Ascenzo, MD
• Phone: +390116335942
• Email: fabrizio.dascenzo[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 550
• Est. completion date: October 15, 2022
• Est. primary completion date: December 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Angina, Stable
• Coronary Artery Disease
• Coronary Disease
• Ischemia
• Left Main Coronary Artery Disease
• Myocardial Ischemia
• Stable Chronic Angina

Intervention

Diagnostic Test:
• coronary computed tomography
patients randomized in this arm will perform computed coronary tomography 6 months after the index percutaneous revascularization on unprotected left main artery

Locations

Country	Name	City	State
Italy	Azienda Ospedaliero-Universitaria di Ferrara	Ferrara
Italy	Ospedale San Luigi Gonzaga, Orbassano	Orbassano
Italy	AOU Città della Salute e della Scienza di Torino	Torino

Sponsors (6)

Lead Sponsor	Collaborator
Azienda Ospedaliera Città della Salute e della Scienza di Torino	Arcispedale Santa Maria Nuova-IRCCS, AUSL Romagna Rimini, Ospedale San Luigi Gonzaga, Orbassano, Ospedale Santa Croce-Carle Cuneo, Università degli Studi di Ferrara

Country where clinical trial is conducted

Italy, 

References & Publications (20)

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Sheiban I, Moretti C, D'Ascenzo F, Chieffo A, Taha S, Connor SO, Chandran S, de la Torre Hernández JM, Chen S, Varbella F, Omedè P, Iannaccone M, Meliga E, Kawamoto H, Montefusco A, Mervyn C, Garot P, Sin L, Gasparetto V, Abdirashid M, Cerrato E, Biondi Zoccai G, Gaita F, Escaned J, Hiddick Smith D, Lefèvre T, Colombo A. Long-Term (=10 Years) Safety of Percutaneous Treatment of Unprotected Left Main Stenosis With Drug-Eluting Stents. Am J Cardiol. 2016 Jul 1;118(1):32-9. doi: 10.1016/j.amjcard.2016.04.007. Epub 2016 Apr 26. — View Citation

Stone GW, Parise H, Witzenbichler B, Kirtane A, Guagliumi G, Peruga JZ, Brodie BR, Dudek D, Möckel M, Lansky AJ, Mehran R. Selection criteria for drug-eluting versus bare-metal stents and the impact of routine angiographic follow-up: 2-year insights from the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial. J Am Coll Cardiol. 2010 Nov 2;56(19):1597-604. doi: 10.1016/j.jacc.2010.08.608. Epub 2010 Oct 1. — View Citation

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* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	AKI	Acute kidney injury (AKI) following CCT will constitute safety end-point	2 days after CCT in the experimental arm
Other	Renal function impairment	reduction of glomerular filtration rate of >24% or end-stage chronic kidney disease	18 months after the index revascularization
Other	Overall bleedings	Any bleeding regardless of severity, defined according to Bleeding Academic Research Consortium (BARC) criteria	18 months after the index revascularization
Other	Major bleedings	BARC bleedings type III-IV-V	18 months after the index revascularization
Other	procedural complications	Procedural complications following each percutaneous coronary intervention (PCI): periprocedural MI defined, arterial access site complications, acute kidney injury	Index hospitalization
Primary	Major adverse cardiovascular events (MACE)	composite and mutual exclusive end point including death, cardiovascular death, myocardial infarction (MI) (excluding periprocedural MI), unstable angina (UA), stent thrombosis	18 months after the index revascularization
Secondary	Target lesion revascularization (TLR)	target lesion revascularization including any TLR, any unplanned TLR and TLR driven by PAC	18 months after the index revascularization
Secondary	All cause death	death from any cause occurring during follow up	within 18 months from the index revascularization
Secondary	stent thrombosis	Any stent thrombosis (definite, probable or possible)	within 18 months from the index revascularization
Secondary	CV death	death from cardiovascular causes	within 18 months from the index revascularization
Secondary	Myocardial infarction	Myocardial infarction defined as non ST elevation acute coronary syndrome (NST-ACS) or ST elevation myocardial infarction (STEMI)	within 18 months from the index revascularization