NCT05818475

Brief 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. 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.

Trial Health

78
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,823

participants targeted

Target at P75+ for not_applicable

Timeline
21mo left

Started May 2023

Longer than P75 for not_applicable

Geographic Reach
2 countries

22 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress63%
May 2023Jan 2028

First Submitted

Initial submission to the registry

March 22, 2023

Completed
27 days until next milestone

First Posted

Study publicly available on registry

April 18, 2023

Completed
20 days until next milestone

Study Start

First participant enrolled

May 8, 2023

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 31, 2026

Completed
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 31, 2028

Expected
Last Updated

May 1, 2026

Status Verified

April 1, 2026

Enrollment Period

2.7 years

First QC Date

March 22, 2023

Last Update Submit

April 27, 2026

Conditions

Keywords

Percutaneous coronary interventionAngiography-derived Fractional Flow ReserveMultivessel disease

Outcome Measures

Primary Outcomes (2)

  • Primary Efficacy Outcome: Patient Oriented Composite Outcome

    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

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

    through study completion, an average of 18 months

Secondary Outcomes (1)

  • Main Secondary Outcome: Cardiovascular Mortality and Myocardial Infarction

    through study completion, an average of 18 months

Study Arms (2)

Angiography-guided PCI

ACTIVE COMPARATOR

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

Angiography-derived FFR PCI indication and planning

EXPERIMENTAL

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

Interventions

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-guided PCI

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.

Angiography-derived FFR PCI indication and planning

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (22)

AUSL Bologna Ospedale Maggiore

Bologna, BO, 40133, Italy

Location

Azienda Ospedaliero Universitaria di Ferrara

Ferrara, FE, 44124, Italy

Location

Ospedale di Bolzano

Bolzano, Italy, 39100, Italy

Location

Azienda Ospedaliero Universitaria Mater Domini

Catanzaro, Italy, Italy

Location

Ospedale Annunziata

Cosenza, Italy, 87100, Italy

Location

Ospedale Civile di Baggiovara

Baggiovara, MO, Italy

Location

AUSL Piacenza

Piacenza, PC, Italy

Location

Azienda Ospedaliero Universitaria di Parma

Parma, PR, Italy

Location

Arcispedale Santa Maria Nuova di Reggio Emilia

Reggio Emilia, RE, 42123, Italy

Location

AUSL Romagna Ospedale degli Infermi Rimini

Rimini, RN, Italy

Location

Ospedale Santa Maria della Misericordia Rovigo

Rovigo, RO, Italy

Location

Ospedale dell'Angelo Mestre

Mestre, VE, 30100, Italy

Location

Ospedale Mater Salutis Legnago

Legnago, VR, Italy

Location

Azienda Ospedaliero Universitaria Integrata di Verona

Verona, VR, Italy

Location

ASST Papa Giovanni XXIII

Bergamo, Italy

Location

AORN Sant'Anna e San Sebastiano

Caserta, Italy

Location

Ospedale Santa Maria Goretti

Latina, Italy

Location

Ospedale Maggiore della Carità Novara

Novara, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, Italy

Location

AUSL Romagna Santa Maria delle Croci Ravenna

Ravenna, Italy

Location

Policlinico Casilino

Roma, Italy

Location

NICVD Karachi

Karachi, Pakistan

Location

Related Publications (10)

  • 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.

    PMID: 28886621BACKGROUND
  • 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.

    PMID: 32294360BACKGROUND
  • 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.

    PMID: 31891653BACKGROUND
  • 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.

    PMID: 34279606BACKGROUND
  • 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.

    PMID: 33541534BACKGROUND
  • 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.

    PMID: 31563688BACKGROUND
  • 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.

    PMID: 34736563BACKGROUND
  • 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.

    PMID: 33999545BACKGROUND
  • 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.

    PMID: 34742368BACKGROUND
  • 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.

MeSH Terms

Conditions

Myocardial Infarction

Condition Hierarchy (Ancestors)

Myocardial IschemiaHeart DiseasesCardiovascular DiseasesVascular DiseasesInfarctionIschemiaPathologic ProcessesPathological Conditions, Signs and SymptomsNecrosis

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Masking Details
Independent Clinical Event Committee blinded to patient's arm
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Study Principal Investigator

Study Record Dates

First Submitted

March 22, 2023

First Posted

April 18, 2023

Study Start

May 8, 2023

Primary Completion

January 31, 2026

Study Completion (Estimated)

January 31, 2028

Last Updated

May 1, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL
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.
Access Criteria
Direct request to study Principal Investigator.

Locations