Cyclosporine and Prognosis in Acute Myocardial Infarction (MI) Patients (CIRCUS)

• total mortality [ Time Frame: at 1 month and 1 year ] [ Designated as safety issue: Yes ]
• cardiovascular death [ Time Frame: at 1 month and 1 year ] [ Designated as safety issue: No ]
• heart failure [ Time Frame: 12 months after acute MI ] [ Designated as safety issue: No ]
  in-hospital worsening of heart failure after reperfusion, or re-hospitalization for: 1) worsening of a heart failure existing at admission, 2) appearance of "new" heart failure
• myocardial infarction [ Time Frame: 12 months after acute MI ] [ Designated as safety issue: No ]
• unstable angina [ Time Frame: 12 months after acute MI ] [ Designated as safety issue: No ]
• stroke [ Time Frame: 12 months after acute MI ] [ Designated as safety issue: No ]
• LV remodeling [ Time Frame: 12 months after acute MI ] [ Designated as safety issue: No ]
• Tolerance to medicinal investigational products [ Time Frame: 12 months after acute MI ] [ Designated as safety issue: Yes ]
  Adverse events

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 (or 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 after treatment.

• Drug: Cyclosporin (verum)
  one single intravenous bolus injection of 2.5 mg/Kg
• Drug: Placebo
  One single intravenous bolus injection of Placebo
• Procedure: Echocardiography
  2 days and 1 year after AMI

• Experimental: Cyclosporin
  Interventions:

  • Drug: Cyclosporin (verum)
  • Procedure: Echocardiography
• Placebo Comparator: Control
  Interventions:

  • Drug: Placebo
  • Procedure: Echocardiography

Inclusion Criteria:

• All patients aged over 18, having a health coverage, without any legal protection measure
• 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).
• The culprit coronary artery has to be the LAD and has to be occluded (TIMI flow grade 0-1) at the time of admission coronary angiography.
• Patients undergoing either primary PCI or rescue PCI 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;
• Patients with known hypersensitivity to cyclosporine or to egg, peanut or Soya-bean proteins,
• known renal insufficiency (either known creatinin clearance < 30 ml/min/1.73m² or current medical care for severe renal insufficiency),
• known liver insufficiency,
• 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 or with an active treatment that might modify blood concentration of Cyclosporine (diltiazem, vérapamil…);
• Female patients currently pregnant or women of childbearing age who were not using contraception;
• Patients with any disorder associated with immunological dysfunction more recently than 6 months prior to presentation: cancer, lymphoma, known positive serology for HIV, or hepatitis.