Cyclosporine and Prognosis in Acute Myocardial Infarction (MI) Patients

Study Overview
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Brief Summary
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Infarct size is a major determinant of prognosis after Acute Myocardial Infarction (AMI). The investigators recently reported that cyclosporine A, when administered immediately prior to percutaneous coronary intervention (PCI), can significantly reduce infarct size in STEMI (ST Elevation acute Myocardial Infarction) patients. The objective of the present study is to determine whether cyclosporine can improve STEMI patient clinical outcome. Nine-hundred and seventy two patients with ST elevation MI will be entered into a multicentre, randomized, placebo-controlled, double-blinded study. They will receive one single injection of cyclosporine A (CicloMulsion, verum) or an equivalent volume of placebo prior to reperfusion therapy by PCI. The incidence of the combined endpoint (mortality, hospitalization for heart failure, left ventricular (LV) remodeling) will be assessed at one year and three years after treatment.

Official Title
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Does Cyclosporine ImpRove Clinical oUtcome in ST Elevation Myocardial Infarction Patients

Conditions
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ST Elevation Acute Myocardial Infarction

Intervention / Treatment
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* Drug: Injection of Cyclosporin
* Drug: Placebo
* Procedure: Echocardiography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligibility criteria (for screening before hospital admission): All (male and female) patients, aged over 18, without any legal protection measure, Having a health coverage, Presenting within 12 hours of the onset of chest pain, Who have ST segment elevation ≥0.2 mV in two contiguous leads, For whom the clinical decision was made to treat with percutaneous coronary intervention (PCI). And (further inclusion criteria to be confirmed by the admission coronary-angiography): The culprit coronary artery has to be the LAD The LAD artery has to be occluded (TIMI flow grade 0-1) at the time of admission coronary angiography. Preliminary oral informed consent followed by signed informed consent as soon as possible. Patients undergoing either primary PCI or rescue PCI are eligible for the study. Patients with previous AMI, PCI or coronary artery bypass surgery (CABG) are eligible for the study. Exclusion Criteria: Patients with loss of consciousness or confused Patients with cardiogenic shock Patients with the left circumflex or the right coronary artery (RCA) as the culprit artery, or with evidence of coronary collaterals to the risk region Patients with an opened (TIMI > 1) LAD coronary artery at admission on initial (admission) coronary angiography Patients with 5.2. known hypersensitivity to cyclosporine 5.3. known hypersensitivity to egg, peanut or Soya-bean proteins 5.4. known renal insufficiency (either known creatinin clearance < 30 ml/min/1.73m² or current medical care for severe renal insufficiency) 5.5. known liver insufficiency 5.6. uncontrolled (treated or untreated) hypertension (> 180/110 mmHg) Patients treated with any compound containing Hypericum perforatum (St.-John's-worth) or Stiripentol or Aliskiren or Bosentan or Rosuvastatine Female patients currently pregnant or women of childbearing age who were not using contraception (oral diagnosis). Patients with any disorder associated with immunological dysfunction more recently than 6 months prior to presentation 8.2. cancer, lymphoma 8.3. known positive serology for HIV, or hepatitis

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cyclosporin<br>Injection of Cyclosporin A : one single intravenous bolus injection of 2.5 mg/Kg Echocardiography | Drug: Injection of Cyclosporin<br>* one single intravenous bolus injection of 2.5 mg/Kg<br>* Other names: Cyclosporin A (CicloMulsion, verum);Procedure: Echocardiography<br>* 1 year after AMI<br>|
| Placebo Comparator: Control<br>one single intravenous bolus injection of Placebo Echocardiography | Drug: Placebo<br>* One single intravenous bolus injection of Placebo<br>Procedure: Echocardiography<br>* 1 year after AMI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined incidence of [total mortality; hospitalization for heart failure; LV remodeling (increase of LV end-diastolic volume > 15%)] |  | at 1 year post-AMI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ejection fraction | Functional outcome | at 1 year | 
| Left-Ventricular End-Diastolic Volume (LVEDV) | Functional outcome | at 1 year | 
| Left-Ventricular End-Systolic Volume (LVESV) | Functional outcome | at 1 year | 
| Total mortality |  | at 1 year | 
| Cardiovascular death |  | at 1 year | 
| Heart failure | In-hospital worsening of heart failure after reperfusion, or rehospitalization for: a)worsening of a heart failure existing at admission, b)appearance of new heart failure | at 1 year | 
| Myocardial infarction |  | at 1 year | 
| Unstable angina |  | at 1 year | 
| Stroke |  | at 1 year | 
| Infarct size | Measured by cardiac MRI, only for patients included in participating centers where cardiac MRI is part of the usual post-infarct care | at 1 year | 
| Infarct size: peak Troponin (T or I) | Explorative outcome. Cardiac prognostic factors. | At admission and at 4 hours (+/- 30 minutes) after study treatment administration | 
| Microvascular obstruction (no reflow) | Explorative outcome. Cardiac prognostic factors. | During hospitalization at admission | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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STEMI, cyclosporine, reperfusion injury