AzTrials
AzTrials

Myocardial InfarctionAIR-STEMINCT05818475

Functional Coronary Angiography Guided Revascularization in STEMI

A study testing Angiography-guided PCI and Angiography-derived FFR PCI indication and planning in people with Myocardial Infarction, run by University Hospital of Ferrara at 22 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myocardial Infarction
What is being tested?
Angiography-guided PCI and Angiography-derived FFR PCI indication and planning
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,823 participants
Where
22 sitesin 2 countries
Study dates
8 May 2023to 31 Jan 2028
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)

Trial locations and contacts

22 sites in 2 countries.

22 sites in 2 countries

Italy21 sites

  • Ospedale Civile di Baggiovara

    Baggiovara, MO

  • ASST Papa Giovanni XXIII

    Bergamo

  • AUSL Bologna Ospedale Maggiore

    Bologna, BO, 40133

  • Ospedale di Bolzano

    Bolzano, Italy, 39100

  • AORN Sant'Anna e San Sebastiano

    Caserta

  • Azienda Ospedaliero Universitaria Mater Domini

    Catanzaro, Italy

  • Ospedale Annunziata

    Cosenza, Italy, 87100

  • Azienda Ospedaliero Universitaria di Ferrara

    Ferrara, FE, 44124

  • Ospedale Santa Maria Goretti

    Latina

  • Ospedale Mater Salutis Legnago

    Legnago, VR

  • Ospedale dell'Angelo Mestre

    Mestre, VE, 30100

  • Ospedale Maggiore della Carità Novara

    Novara

  • Azienda Ospedaliero Universitaria di Parma

    Parma, PR

  • AUSL Piacenza

    Piacenza, PC

  • Azienda Ospedaliero Universitaria Pisana

    Pisa

  • AUSL Romagna Santa Maria delle Croci Ravenna

    Ravenna

  • Arcispedale Santa Maria Nuova di Reggio Emilia

    Reggio Emilia, RE, 42123

  • AUSL Romagna Ospedale degli Infermi Rimini

    Rimini, RN

  • Policlinico Casilino

    Roma

  • Ospedale Santa Maria della Misericordia Rovigo

    Rovigo, RO

  • Azienda Ospedaliero Universitaria Integrata di Verona

    Verona, VR

Other trials in Italy

Pakistan1 site

  • NICVD Karachi

    Karachi

Other trials in Pakistan

About this study

Official title: 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:

Read more
  • 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.

Read the 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.
Being tested
Angiography-guided PCI, Angiography-derived FFR PCI indication and planning
Keywords
Percutaneous coronary intervention, Angiography-derived Fractional Flow Reserve, Multivessel disease
Medical subject headings
Myocardial Infarction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Angiography-guided PCIOther

    Non-culprit lesion treatment will be based on visual estimation by angiography. The evaluation of PCI result will be also based only on angiography.

  • Angiography-derived FFR PCI indication and planningOther

    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.

Study groups in NCT05818475
Study groupRoleWhat they receive
Angiography-guided PCIActive comparatorPatients 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.
Receives: Other: Angiography-guided PCI
Angiography-derived FFR PCI indication and planningExperimentalPatients 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.
Receives: Other: Angiography-derived FFR PCI indication and planning

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Primary Efficacy Outcome: Patient Oriented Composite Outcome

    Cumulative occurrence of mortality, cerebrovascular accident, reinfarction, or ischemia-driven revascularization

    Measured: through study completion, an average of 18 months

  2. Primary Safety Outcome: Major Bleeding and Contrast - Associated Acute Kidney Injury

    Cumulative occurrence of contrast-associated acute kidney injury and bleeding BARC 3-5

    Measured: through study completion, an average of 18 months

Secondary outcomes (1)

  1. Main Secondary Outcome: Cardiovascular Mortality and Myocardial Infarction

    Cumulative occurrence of cardiovascular mortality and myocardial infarction

    Measured: through study completion, an average of 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Apr 2023
  2. Study start8 May 2023
  3. Primary completion31 Jan 2026
  4. Study completion31 Jan 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
1,823 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05818475
Sponsor's protocol ID
82/2023/Sper/AOUFe
Acronym
AIR-STEMI
Status last verified
Apr 2026
First submitted
22 Mar 2023
Last updated
1 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimsky P; ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018 Jan 7;39(2):119-177. doi: 10.1093/eurheartj/ehx393. No abstract available.

    PubMed 28886621

  • Mehta SR, Wood DA, Cairns JA. Complete Revascularization with Multivessel PCI for Myocardial Infarction. Reply. N Engl J Med. 2020 Apr 16;382(16):1571-1572. doi: 10.1056/NEJMc2000278. No abstract available.

    PubMed 32294360

  • Pavasini R, Biscaglia S, Barbato E, Tebaldi M, Dudek D, Escaned J, Casella G, Santarelli A, Guiducci V, Gutierrez-Ibanes E, Di Pasquale G, Politi L, Saglietto A, D'Ascenzo F, Campo G. Complete revascularization reduces cardiovascular death in patients with ST-segment elevation myocardial infarction and multivessel disease: systematic review and meta-analysis of randomized clinical trials. Eur Heart J. 2020 Nov 7;41(42):4103-4110. doi: 10.1093/eurheartj/ehz896.

    PubMed 31891653

  • Collison D, Didagelos M, Aetesam-Ur-Rahman M, Copt S, McDade R, McCartney P, Ford TJ, McClure J, Lindsay M, Shaukat A, Rocchiccioli P, Brogan R, Watkins S, McEntegart M, Good R, Robertson K, O'Boyle P, Davie A, Khan A, Hood S, Eteiba H, Berry C, Oldroyd KG. Post-stenting fractional flow reserve vs coronary angiography for optimization of percutaneous coronary intervention (TARGET-FFR). Eur Heart J. 2021 Dec 1;42(45):4656-4668. doi: 10.1093/eurheartj/ehab449.

    PubMed 34279606

  • Biscaglia S, Uretsky B, Barbato E, Collet C, Onuma Y, Jeremias A, Tebaldi M, Hakeem A, Kogame N, Sonck J, Escaned J, Serruys PW, Stone GW, Campo G. Invasive Coronary Physiology After Stent Implantation: Another Step Toward Precision Medicine. JACC Cardiovasc Interv. 2021 Feb 8;14(3):237-246. doi: 10.1016/j.jcin.2020.10.055.

    PubMed 33541534

  • Biscaglia S, Tebaldi M, Brugaletta S, Cerrato E, Erriquez A, Passarini G, Ielasi A, Spitaleri G, Di Girolamo D, Mezzapelle G, Geraci S, Manfrini M, Pavasini R, Barbato E, Campo G. Prognostic Value of QFR Measured Immediately After Successful Stent Implantation: The International Multicenter Prospective HAWKEYE Study. JACC Cardiovasc Interv. 2019 Oct 28;12(20):2079-2088. doi: 10.1016/j.jcin.2019.06.003. Epub 2019 Sep 25.

    PubMed 31563688

  • Rioufol G, Derimay F, Roubille F, Perret T, Motreff P, Angoulvant D, Cottin Y, Meunier L, Cetran L, Cayla G, Harbaoui B, Wiedemann JY, Van Belle E, Pouillot C, Noirclerc N, Morelle JF, Soto FX, Caussin C, Bertrand B, Lefevre T, Dupouy P, Lesault PF, Albert F, Barthelemy O, Koning R, Leborgne L, Barnay P, Chapon P, Armero S, Lafont A, Piot C, Amaz C, Vaz B, Benyahya L, Varillon Y, Ovize M, Mewton N, Finet G; FUTURE Trial Investigators. Fractional Flow Reserve to Guide Treatment of Patients With Multivessel Coronary Artery Disease. J Am Coll Cardiol. 2021 Nov 9;78(19):1875-1885. doi: 10.1016/j.jacc.2021.08.061.

    PubMed 34736563

  • Puymirat E, Cayla G, Simon T, Steg PG, Montalescot G, Durand-Zaleski I, le Bras A, Gallet R, Khalife K, Morelle JF, Motreff P, Lemesle G, Dillinger JG, Lhermusier T, Silvain J, Roule V, Labeque JN, Range G, Ducrocq G, Cottin Y, Blanchard D, Charles Nelson A, De Bruyne B, Chatellier G, Danchin N; FLOWER-MI Study Investigators. Multivessel PCI Guided by FFR or Angiography for Myocardial Infarction. N Engl J Med. 2021 Jul 22;385(4):297-308. doi: 10.1056/NEJMoa2104650. Epub 2021 May 16.

    PubMed 33999545

  • Xu B, Tu S, Song L, Jin Z, Yu B, Fu G, Zhou Y, Wang J, Chen Y, Pu J, Chen L, Qu X, Yang J, Liu X, Guo L, Shen C, Zhang Y, Zhang Q, Pan H, Fu X, Liu J, Zhao Y, Escaned J, Wang Y, Fearon WF, Dou K, Kirtane AJ, Wu Y, Serruys PW, Yang W, Wijns W, Guan C, Leon MB, Qiao S, Stone GW; FAVOR III China study group. Angiographic quantitative flow ratio-guided coronary intervention (FAVOR III China): a multicentre, randomised, sham-controlled trial. Lancet. 2021 Dec 11;398(10317):2149-2159. doi: 10.1016/S0140-6736(21)02248-0. Epub 2021 Nov 4.

    PubMed 34742368

  • Biscaglia S, Erriquez A, Colaiori I, Hakeem A, Mantovani F, Menozzi M, Barbierato M, Arioti M, Bugani G, Scarsini R, D'Amario D, Donazzan L, Polimeni A, Giordan M, Benatti G, Venturi G, Ruozzi M, Moretti F, Monello A, Moscarella E, Versaci F, Shah JA, Guiducci V, Cavazza C, Gallo F, Rubboli A, Borgi M, Lakho AA, Capecchi A, Lanzilotti V, Ottani F, Casella G, Leone AM, Tebaldi M, Pavasini R, Piccolo R, Farina J, Martella D, Campo G; AIR-STEMI Trial Investigators. Complete Revascularization Guided by Functional Coronary Angiography in STEMI. N Engl J Med. 2026 Aug 29. doi: 10.1056/NEJMoa2605373. Online ahead of print.

    PubMed 42670979

  • Heller T, Ong P, Sechtem U, Bekeredjian R. Management of multivessel disease in patients with ST-segment elevation myocardial infarction: questioning routine immediate complete revascularization in all patients. Coron Artery Dis. 2026 Dec 1;37(8):625-633. doi: 10.1097/MCA.0000000000001661. Epub 2026 Jul 10.

    PubMed 42423587

  • Erriquez A, Colaiori I, Hakeem A, Guiducci V, Menozzi M, Barbierato M, Arioti M, D'Amario D, Casella G, Scarsini R, Polimeni A, Donazzan L, Benatti G, Venturi G, Ruozzi M, Giordan M, Monello A, Moretti F, Versaci F, Shah JA, Lakho AA, Mantovani F, Cavazza C, Bugani G, Lanzilotti V, Gallo F, Leone AM, Tebaldi M, Pavasini R, Piccolo R, Verardi FM, Farina J, Caglioni S, Cocco M, Campo G, Biscaglia S. Functional coronary angiography to indicate and guide revascularization in STEMI patients with multivessel disease: Rationale and design of the AIR-STEMI trial. Am Heart J. 2025 Jun;284:71-80. doi: 10.1016/j.ahj.2025.02.012. Epub 2025 Feb 19.

    PubMed 39984150

Questions about this trial

What is this clinical trial studying?

A study testing Angiography-guided PCI and Angiography-derived FFR PCI indication and planning in people with Myocardial Infarction, run by University Hospital of Ferrara at 22 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 1 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in Italy, Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Primary Efficacy Outcome: Patient Oriented Composite Outcome (time frame: through study completion, an average of 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05818475, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in