Effect of Preliminary Administration of Cyclosporine (Sandimmun ®) on Different Markers of Cardiac Ischaemia Induced by Cardiopulmonary Bypass (Ciclo et CEC)

Grenoble Alpes University Hospital Center (CHU)

Status and phase: Terminated; Phase 2

Conditions: Cardiopulmonary Bypass; Coronary Artery Bypass Surgery

Treatments: Drug: Placebo; Drug: Sandimmum

Study type: Interventional

Funder types: Other

Identifiers

NCT01002859

DCIC 08 04

Details and patient eligibility

About

Observe the effect of preliminary cyclosporine administration on different markers of cardiac ischaemia led by the aortic cross-clamp during coronary artery bypass surgery with Cardiopulmonary bypass.

Full description

The coronary artery bypass surgery, in spite of substantial improvements during the last years, is still associated to a post-operative mortality and morbidity: myocardial infarction, heart failure, cardiac arrhythmia, renal failure, Stroke.

These complications are often due to ischaemia - reperfusion injury event. Recent studies showed that in case of cellular stress (in particular during the reperfusion after ischaemia) a not specific pore, called Mitochondrial permeability transition Pore (MPTP), could be opened. That caused the loss of ion homeostasis, then cell death as well as by apoptosis as by necrosis.

Prevent the opening of this MPTP during the myocardial reperfusion after coronary bypass, for example, is an important objective to improve the cardioprotection.

The Cyclosporin A, prevents the MPTP from opening. Several studies have shown an cytoprotection led by cyclosporin A, after ischaemia reperfusion in several models as isolated rats heart, in vivo rats heart and ex vivo myocardial ( atrial ) human tissues.

Recently, a multicentric study performed in humans, during the acute phase of myocardial infarction, showed a reduction of infarct size by approximately 40% in the cyclosporine group compared to control group.

Enrollment: 50 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patient hospitalized for a coronary artery bypass surgery
• Not urgent surgery
• Left ventricular ejection fraction (LVEF)> 40 %
• 18 years and older
• patient who have sign the informed consent form
• Affiliation to the French Social Security.

Exclusion criteria

• Beating heart surgery with or without Cardiopulmonary Bypass
• Patient receiving another surgical gesture combined to the CABG
• Myocardial infarction or vascular cerebral attack less than 30 days
• Previous History of cardiac surgery;
• Renal failure (creatinine > 200 µmol/l)
• Uncontrolled hypertension
• hyperkaliemy;
• hyperuricemy;
• Acute Coronary Syndrome
• Malignant tumor
• Unchecked infection
• Previous intravenous administration of Sandimmun ®;
• allergy to ciclosporin, ethyl alcohol, castor oil or nitrogen
• Pregnant Woman, parturient without contraception, or breast-feeding
• Age < 18 years
• Patient who have not signed the form of consent;
• Patient Under guardianship or being the object of a legal protective measure

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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50 participants in 2 patient groups, including a placebo group

cyclosporin

Active Comparator group

Description:

Intravenous cyclosporin injection.

Treatment:

Drug: Sandimmum

Pacebo

Placebo Comparator group

Description:

Intravenous injection of NaCl solution.

Treatment:

Drug: Placebo