Minimal Invasive Procedure for Myocardial Infarction

Study Overview
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Brief Summary
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In the setting of primary Percutaneous Coronary Intervention (PCI), the investigators hypothesize that a 24-48 hour delay strategy of stenting after successful thrombus aspiration and establishment of Thrombolysis In Myocardial Infarction (TIMI)-3 flow with optimal antithrombotic therapy may decrease the risk of MicroVascular Obstruction (MVO) as assessed by Cardiac Magnetic Resonance Imaging (CMRI).

Detailed Description
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Primary PCI is the reperfusion therapy of choice in patients with acute ST-elevation myocardial infarction (STEMI) [Van de Werf et al. 2008; Kushner et al. 2009]. The first objective in primary PCI is to restore TIMI-3 flow. However, despite restoration of TIMI-3 flow, myocardial reperfusion remains suboptimal in a significant proportion of patients, predominantly as a consequence of the so called myocardial non-reperfusion phenomenon, low/no-reflow phenomenon or MVO. This, in turn, is associated with significant morbidity and mortality [Brodie et al. 2005; Bruder et al. 2008; Hombach et al. 2005; Nijveldt et al. 2008; Thiele et al. 2008; Wu et al. 1998]. Although TIMI flow is well assessed by angiography, contrast-enhanced CMRI remains the gold standard in the assessment of MVO. Indeed, the presence and extent of hypoenhanced areas have been shown to be associated with a poor outcome [Bruder et al. 2008; Hombach et al. 2005; Nijveldt et al. 2008; Wu et al. 1998]. There is now a large body of evidence to suggest that even in patients with TIMI-3 flow on angiography, as many as 60% of these patients will subsequently exhibit MVO with CMRI [Brodie et al. 2005; Bruder et al. 2008; Hombach et al. 2005; Nijveldt et al. 2008; Thiele et al. 2008; Wu et al. 1998]. Our knowledge of the mechanisms of MVO occurrence as well as measures to reduce MVO has been considerably enhanced by recent publications. For instance, Sianos et al. [2007] demonstrated that the thrombus burden at the time of angiography is an independent predictor of MVO extension and 2-year mortality. Furthermore, Isaaz et al. [2006] recommended a two-step strategy as a means of minimising the risk of MVO, with the first step consisting of TIMI-3 flow restoration, followed 2-6 days later by further angiography to determine the therapeutic strategy of choice (PCI, cardiac surgery, or medical treatment: 67%, 25%, and 8% respectively). Meneveau et al. [2009] also adopted a two-step strategy in a small cohort of STEMI patients with TIMI-3 flow and ST-segment regression at the time of the procedure. They demonstrated that a 24-hour delay in stent implantation led to a higher rate of procedural success than immediate stenting. Isaaz et al. [2006] and Meneveau et al. [2009] also reported a decreased thrombus burden and no culprit-artery re-occlusion between the first and the second procedure. Both the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS) [Svilaas et al. 2008] and the thrombectomy with EXPort catheter in Infarct-Related Artery during primary percutaneous coronary intervention (EXPIRA) [Sardella et al. 2009] studies demonstrated the benefits of thrombus aspiration as the first step in primary PCI prior to either ballooning or direct stenting. However, as the effects of stenting upon MVO in the setting of acute STEMI remain poorly understood, we propose a randomized study to evaluate the benefits of a 24-48-hour delay in stent implantation compared to immediate stenting in patients presenting with acute STEMI who will undergo primary PCI.

Official Title
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Patients Presenting With Acute STEMI Treated With Primary PCI : Comparison of the Impact of the MIMI Approach With a Conventional Strategy of Immediate Stenting

Conditions
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ST Elevation Myocardial Infarction

Intervention / Treatment
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* Procedure: MIMI procedure (two-step strategy)
* Procedure: Immediate Stenting (one-step strategy)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with acute STEMI presenting within 12 hours of symptom onset, requiring a primary percutaneous coronary intervention; and written informed consent. Patients will be randomized during the angiography if the initial TIMI flow is 0 or 1 in a major artery and if TIMI-3 flow can be restored after thrombus aspiration and sustained for 10 minutes. Acute STEMI is defined as typical chest pain with 30 minutes of sustained ST-segment elevation >1 mm in two or more consecutive limb leads or >2 mm in two or more precordial leads in the ECG. Major artery is defined as the proximal or mid segment of the left descending artery, the proximal segment of the circumflex artery (before the first marginal), or the right coronary artery before the posterior descendant artery. Exclusion Criteria: Patients less than 18 years' old Pregnant and breast feeding women Patients with a pacemaker, automated implantable cardioverter-defibrillator (AICD), or left bundle branch block Contraindication to abciximab, prasugrel, or clopidogrel Cardiac arrest as initial presentation Current medical condition with a life expectancy of < 6 months Patients not living in France Patients in cardiogenic shock Culprit artery <2.5 mm Absence of informed consent Patients with initial TIMI 2 or 3 flow or no TIMI-3 flow restored after thrombus aspiration Rescue PCI after fibrinolysis Known creatinine clearance < 30 ml/min.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: MIMI procedure (two-step strategy)<br>Thrombus aspiration is performed to achieve TIMI-3 flow. Once TIMI-3 flow is restored and sustained for > 10 minutes, the initial procedure is stopped regardless of the presence of any residual stenosis. A second coronary angiogram is performed 24-48 hours later and the physician is free to decide on the best treatment, i.e. surgery, medical treatment, or stent implantation (drug-eluting stent if indicated for on-label patients). If stenting is required and the thrombus is still too large (greater than twice the artery width), the physician could postpone stent implantation for days or weeks. | Procedure: MIMI procedure (two-step strategy)<br>* A second coronary angiogram is performed 24-48 hours later and the physician is free to decide on the best treatment, i.e. surgery, medical treatment, or stent implantation (drug-eluting stent if indicated for on-label patients). If stenting is required and the thrombus is still too large (greater than twice the artery width), the physician could postpone stent implantation for days or weeks.<br>* Other names: Two-step strategy;|
| Sham Comparator: Immediate Stenting (one-step strategy)<br>The physician is encouraged to implant a stent after the thrombus aspiration (drug-eluting stent if indicated for on-label patients). | Procedure: Immediate Stenting (one-step strategy)<br>* The physician is encouraged to implant a stent after the thrombus aspiration (drug-eluting stent if indicated for on-label patients).<br>* Other names: Immediate Angioplasty;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint is the extent of MVO as assessed by CMRI, expressed as the ratio of MVO/left ventricular mass, in the MIMI and conventional groups. | The primary end-point will be reviewed by an independent CMRI core laboratory blinded to the group and the procedure. MVO is defined as a hypoenhanced subendocardial area in the infarction core 2 or 10 minutes after contrast injection (dark zone). The total myocardial infarction is defined as the sum of hypoenhanced (dark zone) and hyperenhanced (white zone) signals 10 minutes after contrast injection. The CMRI procedure will be standardised with a specific documentation. | day of performing CMRI (between the fourth and the seventh day after randomization) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the MIMI approach and the conventional strategy on TIMI flow, myocardial blush, and ST-segment evolution before and after the first procedure. | Measurements: TIMI flow grade and TIMI frame count (a more sophisticated method for measuring the flow) at the end of the procedure; blush (a more precise evaluation than TIMI flow on angiography); and ST-segment evolution on the electrocardiogram (ECG) before and 60-90 minutes after the first procedure (core laboratory). | before and 60-90 minutes after the first procedure | 
| To measure TIMI flow and myocardial blush at the beginning and at end of the second procedure in the MIMI group, and to compare with those obtained at the end of the first procedure. | Measurements: TIMI flow grade, TIMI frame count, and blush at the beginning and at the end of the second procedure. | at the beginning and one minute after the end of the second procedure | 
| Thrombus burden assessment, and culprit artery diameter between each procedure in the MIMI group | Measurements: Thrombus volume and artery diameter at the thrombus location during the first and second procedure, and diameter of the implanted stent (done at the core laboratory). | during each procedure (0-48 hours) | 
| Assessment of the ST-segment after the second procedure in the MIMI group | Measurements: Maximal ST-segment elevation before and 60-90 minutes after the second procedure (done at the core laboratory). | at the beginning (puncture) and 60-90 min after the end of the second procedure | 
| Assessment of the impact of the MIMI procedure on hospital clinical events, infarction size (on CMRI) and complications due to the second procedure. | The following hospital critical events and complications that occur after the first procedure will be analyzed: cardiogenic shock, acute pulmonary oedema, recurrent myocardial infarction, culprit artery re-occlusion, stroke, major bleeding [Bovill et al. 1991], evaluation of no flow, coronary dissection, recurrent myocardial infarction, chest pain, decelerating angio flow, recurrent ST elevation, troponin elevation, severe renal insufficiency, access site bleeding, and access artery occlusion. Measurement: CMRI infarction size. | from randomisation to an expected average 4 days stay before hospital discharge | 
| Assessment of the clinical impact of the MIMI procedure at 6 months | Measurements: In both groups, follow-up will be undertaken at 6 months by a phone call to the general practitioner, cardiologist or patient, to report the occurrence of: death, recurrent myocardial infarction, hospitalization(s) for cardiac insufficiency, and unscheduled revascularisation. | 6 months after randomization | 
| Assessment of the microcirculatory resistance in patients in whom a pressure endocoronary wire was used. | Measurement: Index of microcirculatory resistance (IMR) just after stenting (first procedure for the conventional group and second procedure for the MIMI group) | after each procedure (0-48 hours) | 
| Hospitalization duration for both procedures | Measurements: Number of days in ICU | expected average time from randomisation to Intensive Care Unit (ICU) discharge of 4 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute STEMI, Thrombus aspiration, Angioplasty, Primary Percutaneous Coronary Intervention