Trial of Cyclosporine for Myocardial Protection During Open Heart Surgery

Study Overview
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Brief Summary
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Administration of cyclosporine has been found to have a myocardial protective effect, improving post-operative cardiac function in patients undergoing percutaneous coronary interventions by diminishing infarct size. The purpose of the proposed study is to conduct a randomized, controlled clinical trial in patients undergoing isolated valvular heart surgery, or coronary artery bypass surgery. Specifically the investigators will evaluate the cardio-protective effects of cyclosporine on post ischemic-arrest myocardium. The two factors will be treatment group and cyclosporine versus placebo.

Detailed Description
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The specific aim of this study is to perform a randomized controlled study to compare the effects of cyclosporine v. placebo on changes in myocardial functioning associated with open heart surgery for isolated valvular or coronary artery bypass procedures. The research question is: Compared to placebo, does administration of cyclosporine just before surgery improve myocardial functioning in terms of: Transthoracic ECHO (TTE) assessment of ejection fraction Cardiac index (CI), mixed venous oxygen saturation (SVO2), systemic vascular resistance (SVR) Length of stay 30-d mortality Angina Scale SF-36 measure of quality of life Measures associated with myocardial function: Cardiac Index Blood glucose level Serum Troponin I level Free Fatty Acid levels Serum CPK-MB levels Serum phosphoratase levels

Official Title
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A Randomized Trial of Cyclosporine for Myocardial Protection During Open Heart Surgery

Conditions
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Cardiac Surgical Procedures

Intervention / Treatment
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* Drug: cyclosporine
* Drug: saline solution


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Men and women, 18 years of age or older Patients with multi-vessel coronary artery disease Patients undergoing isolated valvular heart surgery (aortic/ mitral) Patients undergoing CABG Exclusion Criteria: Patients with cardiac arrest Patients with ventricular fibrillation Patients with cardiogenic shock Patients requiring circulatory arrest Patients with known hypersensitivity to cyclosporine Patients with known renal failure or a GFR <50 ml/min/1.732 Patients with liver failure Patients with uncontrolled hypertension Women who are pregnant or who are of childbearing age and not on contraception Patients with a serum bilirubin level greater than 3 mg/100 mL

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cyclosporine<br>Cyclosporine Group: Patients will receive a dose of cyclosporine just after they are heparinized. They will receive 2.5 mg of cyclosporine (Sandimmune, Novartis) per kilogram of body weight. It will be injected into a central venous line at the time the central venous line is inserted by the anesthesia team. | Drug: cyclosporine<br>* Cyclosporine Patients will receive a dose of cyclosporine just after they are heparinized. They will receive 2.5 mg of cyclosporine (Sandimmune, Novartis) per kilogram of body weight. It will be injected into a central venous line at the time the central venous line is inserted by the anesthesia team.<br>|
| Placebo Comparator: Placebo<br>Placebo: Patients will undergo the cardiac surgery procedures using standard technique. They will have ischemic arrest of the heart with cold blood cardioplegia using standardized methods of myocardial protection or off-pump CABG. The patients in the placebo group will receive a volumetrically equivalent dose of normal saline to the cyclosporine dose. | Drug: saline solution<br>* Placebo Group: Patients will undergo the cardiac surgery procedures using standard technique. They will have ischemic arrest of the heart with cold blood cardioplegia using standardized methods of myocardial protection or off-pump CABG. The patients in the placebo group will receive a volumetrically equivalent dose of normal saline to the cyclosporine dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of Stay (LOS) |  | postoperative to 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Ventricular Ejection Fraction (TTE) |  | postoperative | 
| Cardiac Index |  | postoperative | 
| SVO2 |  | Postoperative | 
| Systemic Vascular Resistance (SVR) |  | postoperative | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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open heart surgery, cyclosporine, myocardial protection