Comparison Between FFR Guided Revascularization Versus Conventional Strategy in Acute STEMI Patients With MVD.

Study Overview
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Brief Summary
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The Compare-Acute trial is a prospective randomised trial in patients with multivessel disease, who are admitted into hospital with a ST-elevation Myocardial Infarction. The purpose of the study is to compare a FFR guided multivessel PCI taking place during the primary PCI with a primary PCI of the culprit vessel only. Patients will be enrolled after successful revascularisation of the culprit vessel. Patients that have at least one lesion with a diameter of stenosis of more than 50% on visual estimation, feasible (operators judgement) for treatment with PCI in a non-infarct related artery, will be randomised either to the FFR guided complete revascularisation arm or staged revascularisation by proven ischemia or persistence of symptoms of angina. Approximately 885 patients will be entered in the study. Study hypothesis: FFR-guided complete percutaneous revascularisation of all flow-limiting stenoses in the non-IRA performed within the same procedure as the primary PCI or within the same hospitalisation will improve clinical outcomes compared to the staged revascularisation, guided by prove of ischemia or clinical judgment, as recommended from the guidelines.

Detailed Description
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Background of the study: At the moment the general opinion is divided over the way the non culprit lesions in patients presenting with STEMI should be treated. While the previous guidelines stead that these lesions should be treated in a second time ( ie not during the primary intervention) the actual guidelines do not touch this argument. The reason is that the studies where the previous guidelines were based are old. Meanwhile small sized randomised trials from EU region have proven favourable outcomes with NON infarct related artery during the primary procedure while registers (non randomised trials) from USA still recommend the staged treatment. For this reason we have decided to perform a randomised study to address this issue incorporating the state of the art diagnosis and treatment, as well as the new medical therapy and PCI techniques. Objective of the study: FFR-guided complete percutaneous revascularisation of all flow-limiting stenoses in the non-IRA performed within the same procedure as the primary PCI or within the same hospitalisation will improve clinical outcomes compared to the staged revascularisation, guided by prove of ischemia or clinical judgment, as recommended from the guidelines Study design: Prospective, 1: 2 randomisation. FFR guided revascularisation during primary PCI (1) versus following actual guidelines (2) Study population: All STEMI patients between 18-85 years who will be treated with primary PCI in < 12 h (more than 12 hr if persisting pain allowed) after the onset of symptoms and have at least one stenosis of >50% in a non-IRA judged feasible for treatment with PCI. Intervention (if applicable): FFR-guided complete percutaneous revascularisation of all flow-limiting stenoses in the non-IRA performed within the same procedure as the primary PCI or within the same hospitalisation will improve clinical outcomes compared to the staged revascularisation, guided by prove of ischemia or clinical judgment, as recommended from the guidelines Primary study parameters/outcome of the study: Composite endpoint of all cause mortality non-fatal Myocardial Infarction, any Revascularisation and Stroke (MACCE) at 12 months

Official Title
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Fractional Flow Reserve Guided Primary Multivessel Percutaneous Coronary Intervention to Improve Guideline Indexed Actual Standard of Care for Treatment of ST-elevation Myocardial Infarction in Patients With Multivessel Coronary Disease

Conditions
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Myocardial Infarction, Multivessel Coronary Artery Disease

Intervention / Treatment
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* Procedure: FFR-guided revascularisation strategy
* Procedure: randomised to guidelines group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients between 18-85 years presenting with STEMI who will be treated with primary PCI in < 12 h after the onset of symptoms* and have at least one stenosis of >50% in a non-IRA on QCA or visual estimation of baseline angiography and judged feasible for treatment with PCI by the operator. Patients with symptoms for more than 12 hr but ongoing angina complaints can be randomised Exclusion Criteria: Left main stem disease (stenosis > 50%) STEMI due to in-stent thrombosis Chronic total occlusion of a non-IRA Severe stenosis with TIMI flow ≤ II of the non-IRA artery. Non-IRA stenosis not amenable for PCI treatment (operators decision) Complicated IRA treatment, with one or more of the following; Extravasation, Permanent no re-flow after IRA treatment (TIMI flow 0-1), Inability to implant a stent Known severe cardiac valve dysfunction that will require surgery in the follow-up period. Killip class III or IV already at presentation or at the completion of culprit lesion treatment. Life expectancy of < 2 years. Intolerance to Aspirin, Clopidogrel, Prasugrel, Ticagrelor, Heparin, Bivaluridin, or Everolimus and known true anaphylaxis to prior contrast media of bleeding diathesis or known coagulopathy. Gastrointestinal or genitourinary bleeding within the prior 3 months, Planned elective surgical procedure necessitating interruption of thienopyridines during the first 6 months post enrolment. Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period. Pregnancy or planning to become pregnant any time after enrolment into this study. Inability to obtain informed consent. Expected lost to follow-up.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: FFR-guided revascularisation strategy<br>In the FFR-group all flow limiting (FFR≤0.80) lesions will receive treatment by PCI and stenting. The non-IRA PCI should be performed during the same intervention. Exceptions can be made for complex lesions where the operator estimates that the revascularisation procedure will require significant contrast overload which may lead to deterioration of cardiac and renal function of the patient. Such procedures can be performed in a second procedure which should take place within the same hospitalisation. All lesions with a FFR measurement of >0.80 will not be treated. | Procedure: FFR-guided revascularisation strategy<br>* FFR-guided revascularisation strategy<br>|
| Placebo Comparator: randomised to guidelines group<br>In the randomised to guidelines group the procedure will stop after the FFR measurements and the patient will be referred to his treating cardiologist who will decide whether a staged PCI of the non-IRA artery should take place. The treating cardiologist will be blinded for the FFR measurements (but not angiographic imaging) and must make a decision based on conventional non-invasive ischemia detecting tests or clinical signs and symptoms i.e. very typical angina symptoms in patients with angiographic significant stenosis). | Procedure: randomised to guidelines group<br>* Staged revascularisation by proven ischemia or persistence of symptoms of angina<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With the Composite Endpoint of MACCE | Number of participants with the composite endpoint of all cause mortality non-fatal Myocardial Infarction, any Revascularisation and Cerebrovascular Events (MACCE) at 12 months between groups | 12 months | 
| Number of Participants With Death From Any Cause | Number of participants with all cause mortality at 12 months between groups | 12 months | 
| Number of Participants With Cardiac Death | Number of participants with Cardiac mortality at 12 months between groups | 12 months | 
| Number of Participants With Spontaneous MI | Number of participants with Spontaneous Myocardial Infarction at 12 months between groups | 12 months | 
| Number of Participants With Periprocedural MI | Number of participants with Periprocedural Myocardial Infarction at 12 months between groups | 12 months | 
| Number of Participants With Revascularization - PCI | Number of participants with revascularization PCI at 12 months between groups | 12 months | 
| Number of Participants With Revascularization - CABG | Number of participants with revascularization CABG at 12 months between groups | 12 months | 
| Number of Participants With Cerebrovascular Event | Number of participants with Cerebrovascular event at 12 months between groups | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Composite Endpoint of NACE (Any First Event) | Number of participants with Composite endpoint of Cardiac death, Myocardial Infarction, any Revascularisation, Stroke and Major bleeding at 12 months (NACE i.e. Net Adverse Clinical Events) | 12 months | 
| Number of Participants With Death From Any Cause or MI | Number of participants with Part of composite NACE-Death from any cause or Myocardial Infarction at 12 months | 12 months | 
| Number of Participants With Major Bleeding | Number of participants with Major bleeding at 12 months - Part of composite NACE | 12 months | 
| Number of Participants With Any Bleeding at 12 Months | Number of participants with any bleeding at 12 months - part of composite endpoint NACE | 12 months | 
| Number of Participants With Any Bleeding at 48 Hours | Number of participants with any bleeding at 48 hours - part of composite endpoint NACE | 48 hours | 
| Number of Participants With Hospitalization | Number of participants with hospitalization for heart failure, unstable angina or chest pain | 12 months | 
| Number of Participants With Revascularization | Number of participants with any revascularization-Part of composite endpoint NACE | 12 months | 
| Number of Participants With Stent Thrombosis | Number of participants with Stent Thrombosis - Part of composite endpoint NACE | 12 months | 
| Number of Participants With Primary Endpoint Outcome MACCE (Any First Event) at 3 Year | Number of participants with Composite primary endpoint MACCE (any first event) at 3 year | 3 year | 
| Number of Participants With All Cause Death at 3 Year | Number of participants with Composite endpoint MACCE (any first event) at 3 year - all cause death | 3 year | 
| Number of Participants With Cardiac Death at 3 Year | Number of participants with Composite endpoint MACCE (any first event) at 3 year - Cardiac death | 3 year | 
| Number of Participants With Spontaneous MI at 3 Year | Number of participants with Composite endpoint MACCE (any first event) at 3 year - Spontaneous MI | 3 year | 
| Number of Participants With Peri-procedural MI at 3 Year | Number of participants with Composite endpoint MACCE (any first event) at 3 year - Peri-procedural MI | 3 year | 
| Number of Participants With Urgent Revascularization at 3 Year | Number of participants with Composite endpoint MACCE (any first event) at 3 year - urgent revascularisation | 3 year | 
| Number of Participants With Elective Revascularization at 3 Year | Number of participants with Composite endpoint MACCE (any first event) at 3 year -elective revascularisation | 3 year | 
| Number of Participants With Cerebrovascular Event | Number of participants with Composite endpoint MACCE (any first event) at 3 year -Cerebrovascular event | 3 year | 
| Number of Participants With Composite Endpoint of NACE (Any First Event) at 3 Year | Number of participants with Composite endpoint of Cardiac death, Myocardial Infarction, any Revascularisation, Stroke and Major bleeding at 3 year (NACE i.e. Net Adverse Clinical Events) | 3 years | 
| Number of Participants With Death From Any Cause or MI | Number of participants with Part of composite NACE-Death from any cause or Myocardial Infarction at 3 year | 3 year | 
| Number of Participants With Major Bleeding at 3 Year | Number of participants with Part of composite endpoint NACE- Major bleeding at 3 year | 3 year | 
| Number of Participants With Hospitalization | Number of participants with Hospitalization for heart failure, unstable angina, MI | 3 year | 
| Number of Participants With Hospitalization at 3 Year | Number of participants with Hospitalization for heart failure, unstable angina, MI and/or chest pain | 3 year | 
| Number of Participants With Stent Thrombosis at 3 Year | Number of participants with Stent Thrombosis at 3 year - Part of composite endpoint NACE | 3 year | 
| Number of Participants With Any Bleeding at 3 Year | Number of participants with any bleeding at 3 year - Part of composite endpoint NACE | 3 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PCI FFR STEMI MVD, FFR guided PCI in acute STEMI patients with MVD