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Functional Assessment in Elderly MI Patients With Multivessel Disease (FIRE)

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ClinicalTrials.gov Identifier: NCT03772743
Recruitment Status : Recruiting
First Posted : December 11, 2018
Last Update Posted : August 20, 2019
Sponsor:
Information provided by (Responsible Party):
Consorzio Futuro in Ricerca

Tracking Information
First Submitted Date  ICMJE December 9, 2018
First Posted Date  ICMJE December 11, 2018
Last Update Posted Date August 20, 2019
Actual Study Start Date  ICMJE July 15, 2019
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 9, 2018)
Patient oriented cardiac events [ Time Frame: 1-year ]
cumulative occurrence of all-cause death, any MI, any stroke, any coronary revascularization
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03772743 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 9, 2018)
  • Patient oriented cardiac events [ Time Frame: 3-year ]
    cumulative occurrence of all-cause death, any MI, any stroke, any coronary revascularization
  • Patient oriented cardiac events [ Time Frame: 5-year ]
    cumulative occurrence of all-cause death, any MI, any stroke, any coronary revascularization
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Functional Assessment in Elderly MI Patients With Multivessel Disease
Official Title  ICMJE Functional Versus Culprit-only Revascularization in Elderly Patients With Myocardial Infarction and Multivessel Disease
Brief 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. 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 Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
All comers, prospective, randomized, multicenter, open-label trial with blinded adjudicated evaluation of outcomes (PROBE).
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Myocardial Infarction
Intervention  ICMJE
  • Other: Culprit-only revascularization
    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
  • Other: Complete functionally-guided revascularization
    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 Arms  ICMJE
  • Culprit-only revascularization
    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.
    Intervention: Other: Culprit-only revascularization
  • Complete functionally-guided revascularization
    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.
    Intervention: Other: Complete functionally-guided revascularization
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 9, 2018)
1385
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2025
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients ≥75 years AND
  2. MI (ST-segment elevation or not ST.segment elevation MI) with indication to invasive management AND
  3. 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
  4. Successful treatment of culprit lesion

Exclusion Criteria:

  1. Planned surgical revascularization
  2. Non-cardiovascular co-morbidity reducing life expectancy to < 1 year
  3. Any factor precluding 1-year follow-up
  4. Prior Coronary Artery Bypass Graft (CABG) Surgery
  5. Impossibility to identify a clear culprit lesion
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 75 Years and older   (Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Veronica Lodolini, Bs 0532236450 ext +39 ldlvnc@unife.it
Contact: Roberta Piadena 0223992999 ext +39 roberta.piadena@advicepharma.com
Listed Location Countries  ICMJE Italy,   Poland,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03772743
Other Study ID Numbers  ICMJE 2018
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: 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
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: After the publication of the manuscripts reporting the primary outcome and the prespecified substudies
URL: http://thefiretrial.com
Responsible Party Consorzio Futuro in Ricerca
Study Sponsor  ICMJE Consorzio Futuro in Ricerca
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Consorzio Futuro in Ricerca
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP