Treatment of Functionally Non-significant Vulnerable Plaques in Patients With Multivessel ST-elevation Myocardial Infarction The VULNERABLE Trial

Study Overview
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Brief Summary
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The study aims to compare a preventive percutaneous coronary intervention (PCI) plus optimal medical treatment (OMT) strategy vs. OMT for treatment of non-functionally significant non-culprit lesions presenting with optical coherence tomography (OCT) findings indicative of vulnerable plaque, in patients with ST-elevation myocardial infarction (STEMI) and multivessel disease.

Detailed Description
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STEMI patients with multivessel disease planned for invasive evaluation of intermediate lesions (40-69% stenosis) are initially investigated with fractional flow reserve (FFR). Patients with FFR ≤ 0.80 are considered as screening failure and treated with PCI. Patients with FFR > 0.80 are then investigated with optical coherence tomography (OCT). Patients without OCT findings of vulnerable plaque are treated with OMT and included in the OMT registry arm. Patients presenting with OCT characteristics of vulnerable plaque are included in the randomized trial comparing PCI with stent implantation plus OMT versus OMT.

Official Title
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Treatment of Functionally Non-significant Vulnerable Plaques in Patients With Multivessel ST-elevation Myocardial Infarction The VULNERABLE Randomized Trial

Conditions
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Coronary Artery Disease, Coronary Disease, Ischemic Heart Disease

Intervention / Treatment
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* Other: FFR>0.80+ OCT with findings indicative of vulnerable plaque
* Other: FFR>0.80+ OCT with findings indicative of vulnerable plaque


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients > 18 years. Successful revascularization of the culprit lesion in patients undergoing coronary angiography due to ST-segment elevation (> 1mm in > 2 contiguous leads, new left bundle branch block, or true posterior MI with ST depression of >1mm in >2 contiguous anterior leads) in the first 72 hours of the symptom's onset. Multivessel coronary disease with non-culprit lesions located in different vessels than the culprit lesion and ranging from 40 to 69% of DS (visual estimated diameter stenosis ) by visual estimate planned for FFR-guided revascularization in staged procedure (>24 hours and <60 days after PCI of the culprit lesion). Non-culprit lesions should be suitable for functional assessment with pressure wire and OCT catheter and should be suitable to be treated with a single 2.0 to 4.5 mm EES (everolimus-eluting stent ). Subject agrees to not participate in any other clinical trial study for a period of 4 years following the inclusion in the study. Informed consent signed. Exclusion Criteria: Inability to provide informed consent. Female of childbearing potential (age <50 years and last menstruation within the last 12 months), who did not undergo tubal ligation, ovariectomy or hysterectomy. Known intolerance to aspirin, heparin, everolimus, contrast material. Unresolved mechanical complication or cardiogenic shock at the staged procedure. Non-culprit study lesions located in the left main coronary artery or in coronary vessels with prior coronary revascularization (PCI or by-pass) or with distal vessel occlusion. Patients with long, bifurcated, severely angulated or severely calcified non-culprit study lesions non suitable to be treated with a single EES implantation. Asthma or known history of bronchial hyper-reactivity. Chronic renal dysfunction with creatinine clearance < 45 ml/min. Severe comorbidities that in the opinion of the local investigators determine the patient's life expectancy < 4 years. Subject is currently participating in another clinical trial that has not yet completed its primary endpoint.

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Optimal Medical Treatment (OMT) + PCI<br> | Other: FFR>0.80+ OCT with findings indicative of vulnerable plaque<br>* Patients received OPTIMAL MEDICAL TREATMENT (OMT)+PCI<br>|
| Active Comparator: Optimal Medical Treatment (OMT)<br> | Other: FFR>0.80+ OCT with findings indicative of vulnerable plaque<br>* OPTIMAL MEDICAL TREATMENT (OMT)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target Vessel Failure (TVF) | TVF as a composite of : Cardiovascular Death Target-vessel related MI Clinically and physiologically-oriented Target vessel revascularization | 4 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac death | To compare Cardiac death between both groups in the randomized arm death. | 4 Years | 
| All-cause Death | To compare all death between both groups in the randomized arm death. | 4 Years | 
| All Myocardial Infarctions | To compare Myocardial Infarctions between both groups in the randomized arm death. death | 4 Years | 
| Target-Vessel Myocardial Infarction | To compare target-vessel myocardial infarction between both groups in the randomized arm. | 4 Years | 
| Revascularizations | To compare all revascularizations between both groups in the randomized arm. | 4 Years | 
| Ischemic-driven target vessel revascularization | To compare ischemic-driven target vessel revascularization between both groups in the randomized arm. | 4 Years | 
| Patient-oriented endpoint of major adverse cardiac events | To compare the patient-oriented endpoint of major adverse cardiac events, a composite of all-cause death, myocardial infarction, and revascularization between both groups in the randomized arm. | 4 Years | 
| Target Vessel Failure (TVF) | To compare the TVF rate between patients included in the OMT group of the randomized arm (presenting with vulnerable plaque) vs. patients included in the OMT registry (without vulnerable plaque). | 4 Years | 
| Fractional Flow Reserve (FFR) | To compare the FFR values between patients with vulnerable plaques (randomized arm) and patients without vulnerable plaques (OMT registry). | 4 years | 
| Minimal lumen area by Optical Coherence Tomography (OCT) | To establish the optimal OCT-derived minimal lumen area cutoff to predict an ischemic FFR in the non-culprit artery in the acute setting. | 4 years | 
| Accuracy of vulnerable plaque assessment by Optical Coherence Tomography (OCT) | To compare the agreement between local operators and the core-laboratory to assess vulnerable plaques by OCT. | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vulnerable Plaque, Optical Coherence Tomography, Fractional Flow Reserve and ST-elevation Myocardial Infarction