Functional Coronary Angiography Guided Revascularization in STEMI (AIR-STEMI)

March 26, 2024 updated by: Simone Biscaglia, University Hospital of Ferrara

Functional Coronary Angiography to Indicate and Guide Revascularization in STEMI Patients With Multivessel Disease

The goal of this multicenter randomized clinical trial is to test the superiority in terms of efficacy of the Angiography-derived fractional flow reserve (AIR) over that based on conventional angiography (ANGIO) strategy in the management of non-culprit lesions in STEMI patients with multivessel disease.

The main questions it aims to answer are:

  • is an Angiography-derived fractional flow reserve strategy superior to a conventional angiography strategy in reducing the occurrence of the composite efficacy endpoint of all-cause death, myocardial infarction, cerebrovascular accident, or ischemia-driven revascularization.
  • is an Angiography-derived fractional flow reserve strategy superior to a conventional angiography strategy in reducing the occurrence of the composite safety endpoint of of contrast-associated acute kidney injury and Bleeding Academic Research Consortium (BARC) type 3-5.

Participants will be randomized after the successful treatment of the culprit lesion to one of the two strategies and prospectively followed-up.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Reperfusion of the culprit lesion through primary PCI is the standard of care in ST-segment elevation myocardial infarction (STEMI) patients, regardless of their age. The actual gold standard for the management of non-culprit lesions in STEMI patients with multivessel disease (MVD) is angiography-guided complete revascularization. The Complete vs Culprit-only Revascularization to Treat Multi-vessel Disease after Primary PCI for STEMI (COMPLETE) trial randomized 4 041 patients with STEMI and MVD. The main finding was the highly significant reduction of new MI occurrence in the complete group (7.9% vs 5.4%, hazard ratio (HR) 0.68, 95% CI 0.53-0.87, p=0.002). Revascularization was obtained largely by angiographic evaluation (>99%).

After COMPLETE, the subsequent step was to ascertain which complete revascularization strategy should be pursued. In particular, physiology-guided revascularization was compared to an angio-guided strategy. The advantages of physiology against angiography are related to: a) lower number of vessels treated, b) lower number of stents implanted; c) avoidance of a second procedure in negative fractional flow reserve (FFR) patients during primary PCI; d) possibility to optimize the procedure from the physiological standpoint after percutaneous coronary intervention (PCI).

In the Flow Evaluation to Guide Revascularization in Multivessel ST-Elevation Myocardial Infarction (FLOWER-MI), patients with STEMI and multivessel disease who had undergone successful PCI of the infarct-related artery were randomly assigned to receive complete revascularization guided by either FFR or angiography. The primary outcome was a composite of death from any cause, nonfatal myocardial infarction, or unplanned hospitalization leading to urgent revascularization at 1 year. FFR-guided revascularization was associated with lower number of stents implanted per patient (1.01±0.99 versus 1.50±0.86). During follow-up, a primary outcome event occurred in 32 of 586 patients (5.5%) in the FFR-guided group and in 24 of 577 patients (4.2%) in the angiography-guided group (hazard ratio, 1.32; 95% confidence interval, 0.78 to 2.23; P = 0.31). Death occurred in 9 patients (1.5%) in the FFR-guided group and in 10 (1.7%) in the angiography-guided group; nonfatal myocardial infarction in 18 (3.1%) and 10 (1.7%), respectively; and unplanned hospitalization leading to urgent revascularization in 15 (2.6%) and 11 (1.9%), respectively.

The results of the FLOWER-MI trial may suggest that physiology can provide a similar outcome if compared to a conventional angio-guided approach. However, some limitation should be acknowledged: i) rate of events was three-times lower than expected suggesting both a selection bias and the need of a higher number of patients to demonstrate any difference among the two groups; ii) all patients in the FFR-group received a staged procedure to perform physiology assessment diluting one of the major advantages in FFR negative patients, namely the avoidance of a second procedure if physiology is negative; iii) in 16% of patients in the physio-guided group FFR was not performed before PCI, whereas in 82% of patients it was not performed after PCI; iv) even if FFR was associated with lower PCIs, periprocedural MI was three times higher if compared to the angio-group, suggesting its possible underreporting in the angio-group.

After the COMPLETE trial2, the actual standard of care in the management of STEMI patients with MVD is complete revascularization based on angiography. However, this approach may lead to over- or under-estimation of lesions in a relevant portion of patients with negative impact on prognosis. Invasive physiology has been consistently shown to be superior if compared to angio-guided strategy, but it is underutilized in clinical practice mainly due to feasibility issues.

A functional coronary angiography could overcome the applicability issues related to invasive physiology. In addition, it is particularly appealing in the evaluation of non-culprit lesions since:

  1. It is possible to acquire projection during primary PCI and perform the analysis off-line
  2. In case of negative assessment, the patient can avoid a second procedure to invasively measure physiology
  3. It is possible to optimize most of the procedures by the physiological standpoint through the utilization of the virtual-PCI planner tool pre-PCI without the need to repeat physiology after PCI.
  4. It has been recently shown that if compared to an angio-guided approach, Angiography-derived FFR was able to reduce the incidence of spontaneous MI by 36% Therefore, a strategy based on functional coronary angiography to indicate and guide PCI could be superior if compared to an angio-guided strategy both from the efficacy (CV death, cerebrovascular accident, MI and ischemia-driven revascularization) and from the safety (BARC 3-5, contrast-associated acute kidney injury) standpoint.

Study Type

Interventional

Enrollment (Estimated)

1800

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Veronica Lodolini, Bsc
  • Phone Number: +39532236450
  • Email: ldlvnc@unife.it

Study Locations

  • Italy
      • Bergamo, Italy
        • Recruiting
        • ASST Papa Giovanni XXIII
        • Contact:
          • Francesco Moretti
      • Bolzano, Italy, 39100
        • Recruiting
        • Ospedale di Bolzano
        • Contact:
          • Luca Donazzan
      • Caserta, Italy
        • Recruiting
        • AORN Sant'Anna e San Sebastiano
        • Contact:
          • Paolo Calabrò
      • Catanzaro, Italy
        • Recruiting
        • Azienda Ospedaliero Universitaria Mater Domini
        • Contact:
          • Annalisa Mongiardo
      • Cosenza, Italy, 87100
        • Recruiting
        • Ospedale Annunziata
        • Contact:
          • Alberto Polimeni
      • Latina, Italy
        • Recruiting
        • Ospedale Santa Maria Goretti
        • Contact:
          • Francesco Versaci
      • Novara, Italy
        • Recruiting
        • Ospedale Maggiore della Carità Novara
        • Contact:
          • Domenico D'Amario
      • Pisa, Italy
        • Recruiting
        • Azienda Ospedaliero Universitaria Pisana
        • Contact:
          • Alessandro Sticchi
      • Ravenna, Italy
        • Recruiting
        • AUSL Romagna Santa Maria delle Croci Ravenna
        • Contact:
          • Manfredi Arioti
      • Roma, Italy
        • Recruiting
        • Policlinico Casilino
        • Contact:
          • Pio Cialdella
    • BO
      • Bologna, BO, Italy, 40133
        • Recruiting
        • AUSL Bologna Ospedale Maggiore
        • Contact:
          • Giulia Bugani, MD
    • FE
      • Ferrara, FE, Italy, 44124
        • Recruiting
        • Azienda Ospedaliero Universitaria di Ferrara
        • Contact:
        • Contact:
    • MO
      • Baggiovara, MO, Italy
        • Recruiting
        • Ospedale Civile di Baggiovara
        • Contact:
          • Marco Ruozzi
    • PC
      • Piacenza, PC, Italy
        • Recruiting
        • AUSL Piacenza
        • Contact:
          • Guido Rusticali
    • PR
      • Parma, PR, Italy
        • Recruiting
        • Azienda Ospedaliero Universitaria di Parma
        • Contact:
          • Giampaolo Niccoli
    • RE
      • Reggio Emilia, RE, Italy, 42123
        • Recruiting
        • Arcispedale Santa Maria Nuova di Reggio Emilia
        • Contact:
          • Francesca Mantovani, MD
    • RN
      • Rimini, RN, Italy
        • Recruiting
        • AUSL Romagna Ospedale degli Infermi Rimini
        • Contact:
          • Mila Menozzi
    • RO
      • Rovigo, RO, Italy
        • Recruiting
        • Ospedale Santa Maria della Misericordia Rovigo
        • Contact:
          • Massimo Giordan
    • VE
      • Mestre, VE, Italy, 30100
        • Recruiting
        • Ospedale dell'Angelo Mestre
        • Contact:
          • Marco Barbierato
    • VR
      • Legnago, VR, Italy
        • Recruiting
        • Ospedale Mater Salutis Legnago
        • Contact:
          • Gabriele Venturi
      • Verona, VR, Italy
        • Recruiting
        • Azienda Ospedaliero Universitaria Integrata di Verona
        • Contact:
          • Roberto Scarsini
  • Pakistan
      • Karachi, Pakistan
        • Recruiting
        • NICVD Karachi
        • Contact:
          • Abdul Hakeem

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • ST-segment elevation myocardial infarction with indication to invasive management
  • Multi-vessel disease defined as at least 1 non-culprit coronary artery lesion at least 2.5 mm in diameter deemed at visual estimation with a diameter stenosis % ranging from 50 to 99% amenable to successful treatment with PCI
  • Successful treatment of culprit lesion

Exclusion Criteria:

  • Planned surgical revascularization
  • Left main as non-culprit lesion
  • Non-cardiovascular co-morbidity reducing life expectancy to < 1 year
  • Any factor precluding 1-year follow-up
  • Prior Coronary Artery Bypass Graft (CABG) Surgery
  • Impossibility to identify a clear culprit lesion
  • Presence of a chronic total occlusion (CTO)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Angiography-guided PCI
Patients will receive PCI of all lesions with at least 50% diameter stenosis at visual estimation. PCI plan and assessment of PCI results will be based on angiography.
Other: Angiography-guided PCI
Non-culprit lesion treatment will be based on visual estimation by angiography. The evaluation of PCI result will be also based only on angiography.
Experimental: Angiography-derived FFR PCI indication and planning
Patients will receive PCI of all lesions with at least 50% diameter stenosis and positive angiography-derived FFR value (≤0.80). PCI planning will be based on the pullback curve obtained by angiography-derived FFR to obtain an optimal post-PCI physiology.
Other: Angiography-derived FFR PCI indication and planning
Non-culprit lesion treatment will be based on angiography-derived FFR result. In case of positive assessment, PCI will be planned according to the virtual PCI plan based on the physiology pullback curve.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary Efficacy Outcome: Patient Oriented Composite Outcome
Time Frame: through study completion, an average of 18 months
Cumulative occurrence of mortality, cerebrovascular accident, reinfarction, or ischemia-driven revascularization
through study completion, an average of 18 months
Primary Safety Outcome: Major Bleeding and Contrast - Associated Acute Kidney Injury
Time Frame: through study completion, an average of 18 months
Cumulative occurrence of contrast-associated acute kidney injury and bleeding BARC 3-5
through study completion, an average of 18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Main Secondary Outcome: Cardiovascular Mortality and Myocardial Infarction
Time Frame: through study completion, an average of 18 months
Cumulative occurrence of cardiovascular mortality and myocardial infarction
through study completion, an average of 18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital of Ferrara

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 8, 2023

Primary Completion (Estimated)

May 8, 2026

Study Completion (Estimated)

May 8, 2028

Study Registration Dates

First Submitted

March 22, 2023

First Submitted That Met QC Criteria

April 5, 2023

First Posted (Actual)

April 18, 2023

Study Record Updates

Last Update Posted (Actual)

March 27, 2024

Last Update Submitted That Met QC Criteria

March 26, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 82/2023/Sper/AOUFe

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The present study is powered for the patient oriented composite endpoint, but not for CV death and MI. In order to obtain compelling evidence on this latter endpoint, the data of the present study will be merged with those of randomized clinical trials sharing the same inclusion and exclusion criteria, randomization and study interventions.

IPD Sharing Time Frame

Data will be available for individual patient level analysis in order to merge our data with other trials sharing inclusion and exclusion criteria. Data will be available after the completion of the primary endpoint.

IPD Sharing Access Criteria

Direct request to study Principal Investigator.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Myocardial Infarction

Clinical Trials on Angiography-guided PCI

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Pakistan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe