Myocardial InfarctionFIRENCT03772743
Functional Assessment in Elderly MI Patients With Multivessel Disease
A study testing Culprit-only revascularization and Complete functionally-guided revascularization in people with Myocardial Infarction, run by Consorzio Futuro in Ricerca at 37 sites in 3 countries.
Trial summary
Elderly patients presenting with myocardial infarction (MI) and multivessel disease are the highest risk population with the worst prognosis. No trial has ever been designed to optimize their outcome. The actual real-life standard of care is, in the best of the cases, culprit only revascularization. Read more about this study
- Who is it for?
- Ages 75 years and older
- Conditions the study is for
- Myocardial Infarction
- What is being tested?
- Culprit-only revascularization and Complete functionally-guided revascularization
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,445 participants
- Where
- 37 sitesin 3 countries
- Study dates
- 15 Jul 2019to 3 Oct 2026
- 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 75 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Patients ≥75 years AND
- MI (ST-segment elevation or not ST.segment elevation MI) with indication to invasive management AND
- 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 AND
- Successful treatment of culprit lesion
Who cannot join
- Planned surgical revascularization
- 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
- Non culprit lesion located in the left main
Trial locations and contacts
37 sites in 3 countries.
37 sites in 3 countries
Italy22 sites
ASP Agrigento
Agrigento
Ospedale Maggiore
Bologna, Bologna
AOU Sant'Anna e San Sebastiano
Caserta
Casa di Cura San Michele Maddaloni
Caserta
AO Cannizzaro
Catania
Maria Cecilia Hospital
Cotignola, Ravenna
AOU Ferrara
Ferrara, Ferrara, 44124
Ospedale della Misericordia
Grosseto
Ospedale Sant.Andrea
La Spezia
AOU Gaetano Martino
Messina
Ospedale dell'Angelo
Mestre
Ospedale Civile di Baggiovara
Modena
Ospedale Santa Croce
Moncalieri
AOU Giaccone
Palermo
Ospedale Santa Maria delle Croci
Ravenna, Ravenna
Arcispedale Santa Maria Nuova
Reggio Emilia, Reggio Emilia
Ospedale Infermi
Rimini, Rimini
AOU Sant'Andrea
Roma
Ospedale SS Annunziata
Savigliano
Ospedale Umberto I
Syracuse
Ospedale di Rivoli
Torino
AOU Integrata di Verona
Verona
Spain10 sites
Complejo Hospitalario de La Coruna
A Coruña
Hospital General Universitario de Ciudad Real
Ciudad Real
Hospital Universitario Lucus Augusti
Lugo
Hospital Clinico San Carlos
Madrid
Hospital General Universitario Gregorio Maranon
Madrid
Hospital Universitario La Paz
Madrid
Complejo Hospitalario Universitario de Santiago
Santiago de Compostela
Hospital Universitario La FE
Valencia
Hospital Clinico Universitario
Valladolid
Hospital Alvaro Conqueiro de Vigo
Vigo
Poland5 sites
Centrum Kardiologii Inwazyjnej, Elektroterapii i Angiologii
Krosno
Centrum Kardiologii Inwazyjnej, Elektroterapii i Angiologii
Nowy Sącz
Centrum Kardiologii Inwazyjnej Elektroterapii i Angiologii
Oświęcim
Centrum Kardiologii Inwazyjnej, Elektroterapii i Angiologii
Pińczów
Podkarpackie Centrum Interwencji Sercowo-Naczyniowych
Sanok
About this study
Official title: Functional Versus Culprit-only Revascularization in Elderly Patients With Myocardial Infarction and Multivessel Disease
Elderly patients presenting with myocardial infarction (MI) and multivessel disease are the highest risk population with the worst prognosis. No trial has ever been designed to optimize their outcome. The actual real-life standard of care is, in the best of the cases, culprit only revascularization. However, real-life registries show that outcome of MI elderly patients treated with this strategy is far from being optimal with at least a 15% rate of cardiac death or myocardial infarction at 1 year. To date, studies on this population have been focused on devices (bare metal stent vs biodegradable drug eluting stent) or on dual antiplatelet regimen (long vs short) and no study was focused on evaluating if complete revascularization is able to improve the prognosis in these patients. The contemporary complete revascularization is represented by a functionally-driven revascularization that recently showed to significantly reduce myocardial infarction rate and outperformed an angio-complete revascularization. Thus, our hypothesis is that a functionally-driven complete revascularization in elderly patients with MI and multivessel disease may improve prognosis compared to the actual standard of care in these patients, namely culprit only revascularization. Being a "strategy" trial, we identified the patient-oriented composite endpoint (POCE) as primary outcome of interest (all cause death, any MI, any stroke, any revascularization).
Several pre-specified substudies have been planned. A detailed list of the substudies is available in the website of the trial (http://www.thefiretrial.com)
Read the detailed description
BACKGROUND OF THE STUDY
Acute myocardial infarction (AMI) is the most frequent clinical presentation in older adults (≥75 years). Registry data shows that up to 65% of patients ≥75 years with AMI has multivessel disease, namely at least one lesion beyond the culprit one with diameter stenosis >50% and located in a coronary artery different from the culprit vessel. Presence of multivessel disease is a marker of worse prognosis. The rate of adverse events, such as death and MI is 3-fold higher in multivessel disease patients if compared to single vessel disease patients. During a 3-5 years follow-up, the number of adverse events related to non-culprit lesions is double than the one related to culprit lesions (data from SWEDEHEART registry and PROSPECT trial). These adverse events are even more frequent in older adults reaching a 15-30% incidence at 1 year. Several studies were focused on older adults with AMI in order to optimize their treatment. The main focus of those studies were: optimal dual antiplatelet therapy (DAPT) duration and type of stent. As for DAPT, data is in favour of a short regimen (1-6 months) as it represents the best balance between ischemic protection and reduction of bleeding events. In both LEADERS FREE and ZEUS trials, age was the main criteria for enrollment and it was considered as a marker of high risk of bleeding event. In the ongoing XIENCE 28 study, age ≥75 years is considered a sufficient criteria to prescribe 28 days of DAPT after stent implantation.
As for stent type, the recent SENIOR trial showed that biodegradable polymer second generation drug eluting stents (DES) are the gold standard in older adults receiving percutaneous coronary interventions (PCI). These stents clearly outperformed bare metal stents with a low event rate in presence of a short DAPT regimen. Thus, at the present time, we have sufficient data to consider biodegradable polymer DES and short DAPT as cornerstones of the treatment in older adults with MI. On the contrary, we have no scientific evidence regarding the best treatment strategy to apply in multivessel disease patients. It is not clear whether to prefer a culprit only strategy or if revascularization of non-culprit lesions is associated to a reduction of adverse events.
Culprit lesion treatment with PCI and stent implantation in MI setting is universally agreed as gold standard since it reduces morbidity and mortality. In the last 10 years, several studies were focused on the treatment of non-culprit lesions. PRAMI, CULPRIT, DANAMI 3 PRIMULTI, COMPARE ACUTE trial tried to assess if a systematic treatment of non-culprit lesions was associated with an improved prognosis if compared to a culprit only strategy. All these studies showed that complete revascularization clearly reduce the risk of repeated revascularizations. However, no study showed a significant impact on death or MI. When pooled in a meta-analysis, we can observe a trend in favour of MI reduction but data cannot be considered as conclusive. In 2019, COMPLETE trial results will be disclosed. In COMPLETE trial, more than 4000 patients were enrolled with consequent power to detect a difference in terms of death and MI. The limits of all the above mentioned studies are that the mean age was around 60 years and that only ST-segment elevated MI (STEMI) patients were included. No study included a relevant portion of patients ≥75 years nor included no-STEMI (NSTEMI) patients. However, a culprit lesion is identifiable in more than 90% of NSTEMI patients and the issue on their management is similar to the one of the STEMI patients. In addiction, in older adults, clinical presentation is as NSTEMI in more than 70% of the cases. Consequently, it is mandatory to generate solid data on the correct treatment strategy in these patients.
In younger adults (<65 years), in concordance with the solid scientific evidences, it is widespread a complete revascularization strategy. In older adults (≥75 years), also guidelines, in absence of clear data, suggest a case-by-case decision and suggest to consider age as one of the determinants of the final decision (Class IIa level of evidence C, ESC NSTEMI guidelines). Both European and American registry data shows clearly that the most frequently applied strategy is the culprit only one, both in STEMI and NSTEMI patients. Also in the LEADERS FREE trial, patients ≥75 years had multivessel disease in 65% of the cases, but in more than 80% of them, treatment was limited to the culprit lesion. In conclusion, the actual gold standard of treatment in older adults with MI and multivessel disease is the culprit-only strategy. The traditional concept of complete revascularization was based on angiography. Operator visually identified the lesions >50% and decided to treat or not each one of them. Contemporary data on fractional flow reserve and instantaneous free-wave ratio demonstrated that an angio-guided strategy is similar to a coin toss in terms of detection of lesions causing ischemia. This leads to unnecessary PCIs or avoided necessary PCIs in more than 50% of the cases. Studies on angio-complete revascularization probably failed to show an MI reduction because of this reason. In addition, long-term follow-up data of lesions functionally deferred shows that the rate of death and MI at 5 years is below 3%. As a consequence, functional revascularization should be considered as contemporary strategy to achieve a real complete revascularization.
- Conditions
- Myocardial Infarction
- Being tested
- Culprit-only revascularization, Complete functionally-guided revascularization
- Keywords
- older adults, multivessel coronary disease, intracoronary physiology, functional assessment
- Medical subject headings
- Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Culprit-only revascularizationOther
Implantation of drug eluting stents with biodegradable polymer with struts ≤65 μ in the culprit lesion of the MI. Each patient should receive revascularization with Supraflex stent or its newer versions
Complete functionally-guided revascularizationOther
Implantation of drug eluting stents with biodegradable polymer with struts ≤65 μ in the culprit lesion of the MI and in all non culprit lesions with positive functional assessment. Each patient should receive revascularization with Supraflex stent or its newer versions
| Study group | Role | What they receive |
|---|---|---|
| Culprit-only revascularization | Other | All patients randomized to culprit only revascularization must not undergo percutaneous coronary intervention (PCI) any lesion except from the culprit lesion already treated at the moment of the randomization. Staged procedures are considered protocol violation. Receives: Other: Culprit-only revascularization |
| Complete functionally-guided revascularization | Other | Patients who are randomized to this strategy will receive revascularization of the culprit lesion and guided by functional assessment on all non-culprit lesions. Functional evaluation is mandatory for all stenosis with diameter stenosis % between 50 and 90% at visual estimation. Revascularization must be guided by functional assessment on all vessels. The system utilized to obtain functional evaluation is left to Operator's discretion. PCI is allowed only if functional evaluation is positive according to the threshold of the chosen functional system. It is suggested to achieve functional complete revascularization within the index procedure, while it is mandatory to obtain it within the index hospitalization. Receives: Other: Complete functionally-guided revascularization |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patient oriented cardiac events
cumulative occurrence of all-cause death, any MI, any stroke, any revascularization
Measured: 1-year
Secondary outcomes (23)
Patient oriented cardiac events
cumulative occurrence of all-cause death, any MI, any stroke, any revascularization
Measured: 3-year
Patient oriented cardiac events
cumulative occurrence of all-cause death, any MI, any stroke, any revascularization
Measured: 5-year
Device oriented composite endpoint
cumulative occurrence of Cardiovascular Death, MI or non-culprit target vessel revascularization
Measured: 1-year
Device oriented composite endpoint
cumulative occurrence of Cardiovascular Death, MI or non-culprit target vessel revascularization
Measured: 3-year
Device oriented composite endpoint
cumulative occurrence of Cardiovascular Death, MI or non-culprit target vessel revascularization
Measured: 5-year
Cardiovascular Death or MI
cumulative occurrence of Cardiovascular Death or MI
Measured: 1-year
Cardiovascular Death or MI
cumulative occurrence of Cardiovascular Death or MI
Measured: 3-year
Cardiovascular Death or MI
cumulative occurrence of Cardiovascular Death or MI
Measured: 5-year
All-cause death or MI
cumulative occurrence of All-cause Death or MI
Measured: 1-year
All-cause death or MI
cumulative occurrence of All-cause Death or MI
Measured: 3-year
All-cause death or MI
cumulative occurrence of All-cause Death or MI
Measured: 5-year
All-cause death
cumulative occurrence of All-cause Death
Measured: 1-year
All-cause death
cumulative occurrence of All-cause Death
Measured: 3-year
All-cause death
cumulative occurrence of All-cause Death
Measured: 5-year
MI
cumulative occurrence of MI
Measured: 1-year
MI
cumulative occurrence of MI
Measured: 3-year
MI
cumulative occurrence of MI
Measured: 5-year
Any revascularization
cumulative occurrence of revascularization
Measured: 1-year
Any revascularization
cumulative occurrence of revascularization
Measured: 3-year
Any revascularization
cumulative occurrence of revascularization
Measured: 5-year
Ischemic Adverse Events in patients interrupting DAPT
cumulative occurrence of CV death, MI, stroke and revascularization in patients interrupting DAPT
Measured: 1-year
Ischemic Adverse Events in patients disrupting DAPT
cumulative occurrence of CV death, MI, stroke and revascularization in patients disrupting DAPT
Measured: 1-year
Contrast-Induced Acute Kidney Injury
cumulative occurrence of Contrast-Induced Acute Kidney Injury
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2018
- Study start15 Jul 2019
- Primary completion30 Oct 2022
- Study completion3 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Myocardial InfarctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Model description
- All comers, prospective, randomized, multicenter, open-label trial with blinded adjudicated evaluation of outcomes (PROBE).
- Masking
- None (open label)
- Enrolment
- 1,445 participants (actual)
Sponsor and investigators
- Lead sponsor
- Consorzio Futuro in Ricerca
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03772743
- Sponsor's protocol ID
- 56/2019/Sper/AOUFe
- Acronym
- FIRE
- Status last verified
- Mar 2026
- First submitted
- 9 Dec 2018
- Last updated
- 2 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be available after motivated request to the Executive Committee of the study. All requests will be evaluated for acceptance. Positive evaluation by the Executive Committee is mandatory before data release
Publications
Biscaglia S, Guiducci V, Santarelli A, Amat Santos I, Fernandez-Aviles F, Lanzilotti V, Varbella F, Fileti L, Moreno R, Giannini F, Colaiori I, Menozzi M, Redondo A, Ruozzi M, Gutierrez Ibanes E, Diez Gil JL, Maietti E, Biondi Zoccai G, Escaned J, Tebaldi M, Barbato E, Dudek D, Colombo A, Campo G. Physiology-guided revascularization versus optimal medical therapy of nonculprit lesions in elderly patients with myocardial infarction: Rationale and design of the FIRE trial. Am Heart J. 2020 Nov;229:100-109. doi: 10.1016/j.ahj.2020.08.007. Epub 2020 Aug 18.
PubMed 32822656Cocco M, Sarti A, Verardi FM, Caglioni S, Farina J, Penzo C, Tumscitz C, Serenelli M, Tezze R, Cantone A, Erriquez A, Campo G, Biscaglia S. Evaluating the Impact of Enhanced Stent Visualization on PCI Outcomes in Older Patients With Multivessel Disease. Catheter Cardiovasc Interv. 2026 Aug 21. doi: 10.1002/ccd.70819. Online ahead of print.
PubMed 42627239Sarti A, Verardi FM, Cavazza C, Erriquez A, Casella G, Guiducci V, Moreno R, Escaned J, Marchini F, Cocco M, Caglioni S, Farina J, Vadala G, Capecchi A, Gallo F, Cerrato E, Menozzi A, Gil JLD, Santos IA, Ruozzi M, Barbierato M, Picchi A, Pavasini R, Scarsini R, Tebaldi M, Campo G, Biscaglia S. Diabetes does not attenuate the benefit of physiology-guided complete revascularization in older patients with myocardial infarction. Cardiovasc Diabetol. 2026 Apr 14;25(1):161. doi: 10.1186/s12933-026-03165-5.
PubMed 41981421Passo BD, Tonet E, Lanzilotti V, Menozzi M, Scarsini R, Picchi A, Ando G, Sarti A, Farina J, Cantone A, Cocco M, Marchini F, Erriquez A, Pavasini R, Verardi FM, Tebaldi M, Campo G, Biscaglia S. Consistent benefit of physiology-guided complete revascularization across the spectrum of frailty in older patients with myocardial infarction: a prespecified analysis of the FIRE trial. Age Ageing. 2026 Apr 4;55(4):afag078. doi: 10.1093/ageing/afag078.
PubMed 41965249Sarti A, Erriquez A, Dal Passo B, Casella G, Guiducci V, Moreno R, Escaned J, Marchini F, Cocco M, Verardi FM, Clo S, Caglioni S, Farina J, Barbato E, Vadala G, Cavazza C, Capecchi A, Gallo F, Campo G, Biscaglia S. Complete Revascularization in Older Patients With Myocardial Infarction With or Without Complex Nonculprit Lesions. Circ Cardiovasc Interv. 2025 Nov;18(11):e015902. doi: 10.1161/CIRCINTERVENTIONS.125.015902. Epub 2025 Oct 3.
PubMed 41039960Biscaglia S, Erriquez A, Guiducci V, Escaned J, Moreno R, Lanzilotti V, Santarelli A, Cerrato E, Sacchetta G, Menozzi A, Amat-Santos I, Diez Gil JL, Ruozzi M, Barbierato M, Fileti L, Picchi A, Pavasini R, Cimaglia P, Colaiori I, Casella G, Menozzi M, Cavazza C, Caretta G, Scarsini R, D'Amico G, Vadala G, Pilato G, Moscarella E, Tebaldi M, Campo G. Physiology-Guided Complete Revascularization in Older Patients With Myocardial Infarction: Three-Year Outcomes of a Randomized Clinical Trial. JAMA Cardiol. 2025 Nov 1;10(11):1130-1137. doi: 10.1001/jamacardio.2025.3099.
PubMed 40879426Cocco M, Campo G, Guiducci V, Casella G, Cavazza C, Cerrato E, Sacchetta G, Moreno R, Menozzi A, Amat Santos I, Diez Gil JL, Scarsini R, Picchi A, Vadala G, Pilato G, Colaiori I, Barbierato M, Arioti M, Pavasini R, Lanzilotti V, Menozzi M, Varbella F, Erriquez A, Biscaglia S. Complete vs Culprit-Only Revascularization in Older Patients With Myocardial Infarction With or Without ST-Segment Elevation. J Am Coll Cardiol. 2024 Nov 12;84(20):2014-2022. doi: 10.1016/j.jacc.2024.07.028. Epub 2024 Aug 31.
PubMed 39217557Campo G, Guiducci V, Escaned J, Moreno R, Casella G, Cavazza C, Cerrato E, Contarini M, Arena M, Iniguez Romo A, Gutierrez Ibanes E, Scarsini R, Vadala G, Ando G, Pilato G, Musto d'Amore S, Capecchi A, Trillo Nouche R, Moscarella E, Gambino A, Pavani M, Zanetti A, Pesenti N, Dudek D, Barbato E, Tebaldi M, Biscaglia S. Health-Status Outcomes in Older Patients With Myocardial Infarction: Physiology-Guided Complete Revascularization Versus Culprit-Only Strategy. Circ Cardiovasc Qual Outcomes. 2024 Jul;17(7):e010490. doi: 10.1161/CIRCOUTCOMES.123.010490. Epub 2024 Jun 18.
PubMed 38887951Cocco M, Campo G. Taking Stent Technology to a New Stage of Safety and Efficacy: Biodegradable Polymer Ultrathin Drug-Eluting Stents. Cardiology. 2024;149(5):420-422. doi: 10.1159/000539341. Epub 2024 Jun 17. No abstract available.
PubMed 38885624Erriquez A, Campo G, Guiducci V, Casella G, Menozzi M, Cerrato E, Sacchetta G, Moreno R, Arena M, Amat Santos I, Diez Gil JL, Scarsini R, Ruozzi M, Arioti M, Picchi A, Barbierato M, Moscarella E, Musto D'Amore S, Lanzilotti V, Cavazza C, Rezzaghi M, Cocco M, Marrone A, Verardi FM, Escaned J, Barbato E, Colaiori I, Pesenti N, Carrara G, Biscaglia S. QFR for the Revascularization of Nonculprit Vessels in MI Patients: Insights From the FIRE Trial. JACC Cardiovasc Interv. 2024 Jun 24;17(12):1425-1436. doi: 10.1016/j.jcin.2024.04.022. Epub 2024 May 14.
PubMed 38752972Erriquez A, Campo G, Guiducci V, Escaned J, Moreno R, Casella G, Menozzi M, Cerrato E, Sacchetta G, Menozzi A, Santos IA, Ibanes EG, Scarsini R, Vadala G, Ando G, Diez-Gil JL, d'Amore SM, Capecchi A, Colaiori I, Gallo F, Pavasini R, Marrone A, Pompei G, Lanzilotti V, Dudek D, Barbato E, Tebaldi M, Biscaglia S. Complete vs Culprit-Only Revascularization in Older Patients With Myocardial Infarction and High Bleeding Risk: A Randomized Clinical Trial. JAMA Cardiol. 2024 Jun 1;9(6):565-573. doi: 10.1001/jamacardio.2024.0804.
PubMed 38717753Pavasini R, Campo G, Serenelli M, Tonet E, Guiducci V, Escaned J, Moreno R, Casella G, Cavazza C, Varbella F, Sacchetta G, Arena M, Santos IA, Ibanes EG, Scarsini R, D'Amico G, Ruiz-Poveda FL, Diez Gil JL, Pignatelli G, Iannopollo G, Colaiori I, Santos RC, Marrone A, Fileti L, Rigattieri S, Barbato E, Ocaranza-Sanchez R, Biscaglia S. Impact of pre-admission physical activity on benefits of physiology-guided complete revascularization in older patients with myocardial infarction: insights from the FIRE trial. Eur J Prev Cardiol. 2024 Sep 6;31(12):1451-1459. doi: 10.1093/eurjpc/zwae069.
PubMed 38452238Biscaglia S, Guiducci V, Escaned J, Moreno R, Lanzilotti V, Santarelli A, Cerrato E, Sacchetta G, Jurado-Roman A, Menozzi A, Amat Santos I, Diez Gil JL, Ruozzi M, Barbierato M, Fileti L, Picchi A, Lodolini V, Biondi-Zoccai G, Maietti E, Pavasini R, Cimaglia P, Tumscitz C, Erriquez A, Penzo C, Colaiori I, Pignatelli G, Casella G, Iannopollo G, Menozzi M, Varbella F, Caretta G, Dudek D, Barbato E, Tebaldi M, Campo G; FIRE Trial Investigators. Complete or Culprit-Only PCI in Older Patients with Myocardial Infarction. N Engl J Med. 2023 Sep 7;389(10):889-898. doi: 10.1056/NEJMoa2300468. Epub 2023 Aug 26.
PubMed 37634150
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Functional Versus Culprit-only Revascularization in Elderly Patients With Myocardial Infarction and Multivessel Disease
- ClinicalTrials.gov ID
- NCT03772743
- Acronym / sponsor ID
- FIRE / 56/2019/Sper/AOUFe
- Conditions
- Myocardial Infarction
- Keywords
- older adults, multivessel coronary disease, intracoronary physiology, functional assessment
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 1,445 participants (actual)
- Lead sponsor
- Consorzio Futuro in RicercaUniversity, hospital or other
- Study start
- 15 Jul 2019 (actual)
- Primary completion
- 30 Oct 2022 (actual)
- Study completion
- 3 Oct 2026 (estimated)
- First posted
- 11 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Elderly patients presenting with myocardial infarction (MI) and multivessel disease are the highest risk population with the worst prognosis. No trial has ever been designed to optimize their outcome. The actual real-life standard of care is, in the best of the cases, culprit only revascularization. However, real-life registries show that outcome of MI elderly patients treated with this strategy is far from being optimal with at least a 15% rate of cardiac death or myocardial infarction at 1 year. To date, studies on this population have been focused on devices (bare metal stent vs biodegradable drug eluting stent) or on dual antiplatelet regimen (long vs short) and no study was focused on evaluating if complete revascularization is able to improve the prognosis in these patients. The contemporary complete revascularization is represented by a functionally-driven revascularization that recently showed to significantly reduce myocardial infarction rate and outperformed an angio-complete revascularization. Thus, our hypothesis is that a functionally-driven complete revascularization in elderly patients with MI and multivessel disease may improve prognosis compared to the actual standard of care in these patients, namely culprit only revascularization. Being a "strategy" trial, we identified the patient-oriented composite endpoint (POCE) as primary outcome of interest (all cause death, any MI, any stroke, any revascularization).
Several pre-specified substudies have been planned. A detailed list of the substudies is available in the website of the trial (http://www.thefiretrial.com)
Detailed description
BACKGROUND OF THE STUDY
Acute myocardial infarction (AMI) is the most frequent clinical presentation in older adults (≥75 years). Registry data shows that up to 65% of patients ≥75 years with AMI has multivessel disease, namely at least one lesion beyond the culprit one with diameter stenosis >50% and located in a coronary artery different from the culprit vessel. Presence of multivessel disease is a marker of worse prognosis. The rate of adverse events, such as death and MI is 3-fold higher in multivessel disease patients if compared to single vessel disease patients. During a 3-5 years follow-up, the number of adverse events related to non-culprit lesions is double than the one related to culprit lesions (data from SWEDEHEART registry and PROSPECT trial). These adverse events are even more frequent in older adults reaching a 15-30% incidence at 1 year. Several studies were focused on older adults with AMI in order to optimize their treatment. The main focus of those studies were: optimal dual antiplatelet therapy (DAPT) duration and type of stent. As for DAPT, data is in favour of a short regimen (1-6 months) as it represents the best balance between ischemic protection and reduction of bleeding events. In both LEADERS FREE and ZEUS trials, age was the main criteria for enrollment and it was considered as a marker of high risk of bleeding event. In the ongoing XIENCE 28 study, age ≥75 years is considered a sufficient criteria to prescribe 28 days of DAPT after stent implantation.
As for stent type, the recent SENIOR trial showed that biodegradable polymer second generation drug eluting stents (DES) are the gold standard in older adults receiving percutaneous coronary interventions (PCI). These stents clearly outperformed bare metal stents with a low event rate in presence of a short DAPT regimen. Thus, at the present time, we have sufficient data to consider biodegradable polymer DES and short DAPT as cornerstones of the treatment in older adults with MI. On the contrary, we have no scientific evidence regarding the best treatment strategy to apply in multivessel disease patients. It is not clear whether to prefer a culprit only strategy or if revascularization of non-culprit lesions is associated to a reduction of adverse events.
Culprit lesion treatment with PCI and stent implantation in MI setting is universally agreed as gold standard since it reduces morbidity and mortality. In the last 10 years, several studies were focused on the treatment of non-culprit lesions. PRAMI, CULPRIT, DANAMI 3 PRIMULTI, COMPARE ACUTE trial tried to assess if a systematic treatment of non-culprit lesions was associated with an improved prognosis if compared to a culprit only strategy. All these studies showed that complete revascularization clearly reduce the risk of repeated revascularizations. However, no study showed a significant impact on death or MI. When pooled in a meta-analysis, we can observe a trend in favour of MI reduction but data cannot be considered as conclusive. In 2019, COMPLETE trial results will be disclosed. In COMPLETE trial, more than 4000 patients were enrolled with consequent power to detect a difference in terms of death and MI. The limits of all the above mentioned studies are that the mean age was around 60 years and that only ST-segment elevated MI (STEMI) patients were included. No study included a relevant portion of patients ≥75 years nor included no-STEMI (NSTEMI) patients. However, a culprit lesion is identifiable in more than 90% of NSTEMI patients and the issue on their management is similar to the one of the STEMI patients. In addiction, in older adults, clinical presentation is as NSTEMI in more than 70% of the cases. Consequently, it is mandatory to generate solid data on the correct treatment strategy in these patients.
In younger adults (<65 years), in concordance with the solid scientific evidences, it is widespread a complete revascularization strategy. In older adults (≥75 years), also guidelines, in absence of clear data, suggest a case-by-case decision and suggest to consider age as one of the determinants of the final decision (Class IIa level of evidence C, ESC NSTEMI guidelines). Both European and American registry data shows clearly that the most frequently applied strategy is the culprit only one, both in STEMI and NSTEMI patients. Also in the LEADERS FREE trial, patients ≥75 years had multivessel disease in 65% of the cases, but in more than 80% of them, treatment was limited to the culprit lesion. In conclusion, the actual gold standard of treatment in older adults with MI and multivessel disease is the culprit-only strategy. The traditional concept of complete revascularization was based on angiography. Operator visually identified the lesions >50% and decided to treat or not each one of them. Contemporary data on fractional flow reserve and instantaneous free-wave ratio demonstrated that an angio-guided strategy is similar to a coin toss in terms of detection of lesions causing ischemia. This leads to unnecessary PCIs or avoided necessary PCIs in more than 50% of the cases. Studies on angio-complete revascularization probably failed to show an MI reduction because of this reason. In addition, long-term follow-up data of lesions functionally deferred shows that the rate of death and MI at 5 years is below 3%. As a consequence, functional revascularization should be considered as contemporary strategy to achieve a real complete revascularization.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- All comers, prospective, randomized, multicenter, open-label trial with blinded adjudicated evaluation of outcomes (PROBE).
| Arm | Type | Receives |
|---|---|---|
| Culprit-only revascularization | Other | Other: Culprit-only revascularizationAll patients randomized to culprit only revascularization must not undergo percutaneous coronary intervention (PCI) any lesion except from the culprit lesion already treated at the moment of the randomization. Staged procedures are considered protocol violation. |
| Complete functionally-guided revascularization | Other | Other: Complete functionally-guided revascularizationPatients who are randomized to this strategy will receive revascularization of the culprit lesion and guided by functional assessment on all non-culprit lesions. Functional evaluation is mandatory for all stenosis with diameter stenosis % between 50 and 90% at visual estimation. Revascularization must be guided by functional assessment on all vessels. The system utilized to obtain functional evaluation is left to Operator's discretion. PCI is allowed only if functional evaluation is positive according to the threshold of the chosen functional system. It is suggested to achieve functional complete revascularization within the index procedure, while it is mandatory to obtain it within the index hospitalization. |
Who may qualify
- Ages
- 75 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (4 listed)
- Patients ≥75 years AND
- MI (ST-segment elevation or not ST.segment elevation MI) with indication to invasive management AND
- 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 AND
- Successful treatment of culprit lesion
Key exclusion criteria (6 listed)
- Planned surgical revascularization
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Culprit-only revascularizationImplantation of drug eluting stents with biodegradable polymer with struts ≤65 μ in the culprit lesion of the MI. Each patient should receive revascularization with Supraflex stent or its newer versions | Other | Culprit-only revascularization |
| Complete functionally-guided revascularizationImplantation of drug eluting stents with biodegradable polymer with struts ≤65 μ in the culprit lesion of the MI and in all non culprit lesions with positive functional assessment. Each patient should receive revascularization with Supraflex stent or its newer versions | Other | Complete functionally-guided revascularization |
Primary outcome
Patient oriented cardiac events
Time frame: 1-year
cumulative occurrence of all-cause death, any MI, any stroke, any revascularization
23 secondary outcomes
Patient oriented cardiac events
Time frame: 3-year
Patient oriented cardiac events
Time frame: 5-year
Device oriented composite endpoint
Time frame: 1-year
Device oriented composite endpoint
Time frame: 3-year
Device oriented composite endpoint
Time frame: 5-year
Cardiovascular Death or MI
Time frame: 1-year
Cardiovascular Death or MI
Time frame: 3-year
Cardiovascular Death or MI
Time frame: 5-year
All-cause death or MI
Time frame: 1-year
All-cause death or MI
Time frame: 3-year
All-cause death or MI
Time frame: 5-year
All-cause death
Time frame: 1-year
All-cause death
Time frame: 3-year
All-cause death
Time frame: 5-year
MI
Time frame: 1-year
MI
Time frame: 3-year
MI
Time frame: 5-year
Any revascularization
Time frame: 1-year
Any revascularization
Time frame: 3-year
Any revascularization
Time frame: 5-year
Ischemic Adverse Events in patients interrupting DAPT
Time frame: 1-year
Ischemic Adverse Events in patients disrupting DAPT
Time frame: 1-year
Contrast-Induced Acute Kidney Injury
Time frame: 1 month
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2026.
- Background: PubMed 32822656Biscaglia S, Guiducci V, Santarelli A, Amat Santos I, Fernandez-Aviles F, Lanzilotti V, Varbella F, Fileti L, Moreno R, Giannini F, Colaiori I, Menozzi M, Redondo A, Ruozzi M, Gutierrez Ibanes E, Diez Gil JL, Maietti E, Biondi Zoccai G, Escaned J, Tebaldi M, Barbato E, Dudek D, Colombo A, Campo G. Physiology-guided revascularization versus optimal medical therapy of nonculprit lesions in elderly patients with myocardial infarction: Rationale and design of the FIRE trial. Am Heart J. 2020 Nov;229:100-109. doi: 10.1016/j.ahj.2020.08.007. Epub 2020 Aug 18.
- Derived from this study: PubMed 42627239Cocco M, Sarti A, Verardi FM, Caglioni S, Farina J, Penzo C, Tumscitz C, Serenelli M, Tezze R, Cantone A, Erriquez A, Campo G, Biscaglia S. Evaluating the Impact of Enhanced Stent Visualization on PCI Outcomes in Older Patients With Multivessel Disease. Catheter Cardiovasc Interv. 2026 Aug 21. doi: 10.1002/ccd.70819. Online ahead of print.
- Derived from this study: PubMed 41981421Sarti A, Verardi FM, Cavazza C, Erriquez A, Casella G, Guiducci V, Moreno R, Escaned J, Marchini F, Cocco M, Caglioni S, Farina J, Vadala G, Capecchi A, Gallo F, Cerrato E, Menozzi A, Gil JLD, Santos IA, Ruozzi M, Barbierato M, Picchi A, Pavasini R, Scarsini R, Tebaldi M, Campo G, Biscaglia S. Diabetes does not attenuate the benefit of physiology-guided complete revascularization in older patients with myocardial infarction. Cardiovasc Diabetol. 2026 Apr 14;25(1):161. doi: 10.1186/s12933-026-03165-5.
- Derived from this study: PubMed 41965249Passo BD, Tonet E, Lanzilotti V, Menozzi M, Scarsini R, Picchi A, Ando G, Sarti A, Farina J, Cantone A, Cocco M, Marchini F, Erriquez A, Pavasini R, Verardi FM, Tebaldi M, Campo G, Biscaglia S. Consistent benefit of physiology-guided complete revascularization across the spectrum of frailty in older patients with myocardial infarction: a prespecified analysis of the FIRE trial. Age Ageing. 2026 Apr 4;55(4):afag078. doi: 10.1093/ageing/afag078.
- Derived from this study: PubMed 41039960Sarti A, Erriquez A, Dal Passo B, Casella G, Guiducci V, Moreno R, Escaned J, Marchini F, Cocco M, Verardi FM, Clo S, Caglioni S, Farina J, Barbato E, Vadala G, Cavazza C, Capecchi A, Gallo F, Campo G, Biscaglia S. Complete Revascularization in Older Patients With Myocardial Infarction With or Without Complex Nonculprit Lesions. Circ Cardiovasc Interv. 2025 Nov;18(11):e015902. doi: 10.1161/CIRCINTERVENTIONS.125.015902. Epub 2025 Oct 3.
- Derived from this study: PubMed 40879426Biscaglia S, Erriquez A, Guiducci V, Escaned J, Moreno R, Lanzilotti V, Santarelli A, Cerrato E, Sacchetta G, Menozzi A, Amat-Santos I, Diez Gil JL, Ruozzi M, Barbierato M, Fileti L, Picchi A, Pavasini R, Cimaglia P, Colaiori I, Casella G, Menozzi M, Cavazza C, Caretta G, Scarsini R, D'Amico G, Vadala G, Pilato G, Moscarella E, Tebaldi M, Campo G. Physiology-Guided Complete Revascularization in Older Patients With Myocardial Infarction: Three-Year Outcomes of a Randomized Clinical Trial. JAMA Cardiol. 2025 Nov 1;10(11):1130-1137. doi: 10.1001/jamacardio.2025.3099.
- Derived from this study: PubMed 39217557Cocco M, Campo G, Guiducci V, Casella G, Cavazza C, Cerrato E, Sacchetta G, Moreno R, Menozzi A, Amat Santos I, Diez Gil JL, Scarsini R, Picchi A, Vadala G, Pilato G, Colaiori I, Barbierato M, Arioti M, Pavasini R, Lanzilotti V, Menozzi M, Varbella F, Erriquez A, Biscaglia S. Complete vs Culprit-Only Revascularization in Older Patients With Myocardial Infarction With or Without ST-Segment Elevation. J Am Coll Cardiol. 2024 Nov 12;84(20):2014-2022. doi: 10.1016/j.jacc.2024.07.028. Epub 2024 Aug 31.
- Derived from this study: PubMed 38887951Campo G, Guiducci V, Escaned J, Moreno R, Casella G, Cavazza C, Cerrato E, Contarini M, Arena M, Iniguez Romo A, Gutierrez Ibanes E, Scarsini R, Vadala G, Ando G, Pilato G, Musto d'Amore S, Capecchi A, Trillo Nouche R, Moscarella E, Gambino A, Pavani M, Zanetti A, Pesenti N, Dudek D, Barbato E, Tebaldi M, Biscaglia S. Health-Status Outcomes in Older Patients With Myocardial Infarction: Physiology-Guided Complete Revascularization Versus Culprit-Only Strategy. Circ Cardiovasc Qual Outcomes. 2024 Jul;17(7):e010490. doi: 10.1161/CIRCOUTCOMES.123.010490. Epub 2024 Jun 18.
- Derived from this study: PubMed 38885624Cocco M, Campo G. Taking Stent Technology to a New Stage of Safety and Efficacy: Biodegradable Polymer Ultrathin Drug-Eluting Stents. Cardiology. 2024;149(5):420-422. doi: 10.1159/000539341. Epub 2024 Jun 17. No abstract available.
- Derived from this study: PubMed 38752972Erriquez A, Campo G, Guiducci V, Casella G, Menozzi M, Cerrato E, Sacchetta G, Moreno R, Arena M, Amat Santos I, Diez Gil JL, Scarsini R, Ruozzi M, Arioti M, Picchi A, Barbierato M, Moscarella E, Musto D'Amore S, Lanzilotti V, Cavazza C, Rezzaghi M, Cocco M, Marrone A, Verardi FM, Escaned J, Barbato E, Colaiori I, Pesenti N, Carrara G, Biscaglia S. QFR for the Revascularization of Nonculprit Vessels in MI Patients: Insights From the FIRE Trial. JACC Cardiovasc Interv. 2024 Jun 24;17(12):1425-1436. doi: 10.1016/j.jcin.2024.04.022. Epub 2024 May 14.
- Derived from this study: PubMed 38717753Erriquez A, Campo G, Guiducci V, Escaned J, Moreno R, Casella G, Menozzi M, Cerrato E, Sacchetta G, Menozzi A, Santos IA, Ibanes EG, Scarsini R, Vadala G, Ando G, Diez-Gil JL, d'Amore SM, Capecchi A, Colaiori I, Gallo F, Pavasini R, Marrone A, Pompei G, Lanzilotti V, Dudek D, Barbato E, Tebaldi M, Biscaglia S. Complete vs Culprit-Only Revascularization in Older Patients With Myocardial Infarction and High Bleeding Risk: A Randomized Clinical Trial. JAMA Cardiol. 2024 Jun 1;9(6):565-573. doi: 10.1001/jamacardio.2024.0804.
- Derived from this study: PubMed 38452238Pavasini R, Campo G, Serenelli M, Tonet E, Guiducci V, Escaned J, Moreno R, Casella G, Cavazza C, Varbella F, Sacchetta G, Arena M, Santos IA, Ibanes EG, Scarsini R, D'Amico G, Ruiz-Poveda FL, Diez Gil JL, Pignatelli G, Iannopollo G, Colaiori I, Santos RC, Marrone A, Fileti L, Rigattieri S, Barbato E, Ocaranza-Sanchez R, Biscaglia S. Impact of pre-admission physical activity on benefits of physiology-guided complete revascularization in older patients with myocardial infarction: insights from the FIRE trial. Eur J Prev Cardiol. 2024 Sep 6;31(12):1451-1459. doi: 10.1093/eurjpc/zwae069.
- Individual participant dataSharing planned: Yes. Data will be available after motivated request to the Executive Committee of the study. All requests will be evaluated for acceptance. Positive evaluation by the Executive Committee is mandatory before data release
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
37 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Culprit-only revascularization and Complete functionally-guided revascularization in people with Myocardial Infarction, run by Consorzio Futuro in Ricerca at 37 sites in 3 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 4 inclusion and 6 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 2 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 37 sites in Italy, Spain, Poland. 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?
Patient oriented cardiac events (time frame: 1-year). 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 NCT03772743, which also lists 13 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 2 Apr 2026.