Effects of Remote Ischemic PreConditioning in Off-pump Versus On-pump Coronary Artery Bypass Grafting(RIPCON)

Study Overview
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Brief Summary
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Purpose Remote ischemic preconditioning (RIPC) with transient upper limb ischemia reduces myocardial injury in patients undergoing On-pump coronary artery bypass (CABG) surgery with cross-clamp fibrillation or blood cardioplegia for myocardial protection. The molecular mechanisms leading to these effects are yet not fully understood. The purpose of the present study is to validate previous studies and gather further evidence for RIPC during CABG with blood cardioplegia, furthermore to determine, whether or not RIPC is still operative during Off-pump coronary artery bypass surgery (OPCAB), finally to elucidate intra-cellular mechanisms involved in myocardial protection by RIPC and their possible systemic mediators.

Detailed Description
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Remote ischemic preconditioning (RIPC) protocol before CABG (study arm A) or OPCAB (study arm B) consists of 3 cycles of 5 minutes left upper arm ischemia by inflation of a blood pressure cuff to 200 mmHg and 5 minutes of reperfusion after induction of anesthesia before coronary artery bypass surgery. For myocardial molecular analyses, left ventricular biopsies are taken before induction of cardioplegic cardiac arrest (A) or first coronary incision (B), and 5 to 10 minutes after aortic unclamping during reperfusion of the myocardium (A) or 5 to 10 minutes after the completion of the last anastomosis (B). Blood samples are taken prior to RIPC and during the first three postoperative days.

Official Title
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Effects of Remote Ischemic PreConditioning in Off-pump Versus On-pump Coronary

Conditions
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Myocardial Injury

Intervention / Treatment
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* Procedure: Remote ischemic preconditioning (RIPC)
* Procedure: Coronary artery bypass grafting (CABG) without remote ischemic preconditioning protocol
* Procedure: Off-pump Coronary artery bypass surgery without remote ischemic preconditioning


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed triple vessel coronary artery disease Indication for surgical coronary revascularisation Written informed consent Age ≥ 18 years Exclusion Criteria: Age > 80 years Instable angina/acute coronary syndrome Emergency surgery Recent myocardial infarction within 7 days prior to surgery Recent major infection/sepsis within 7 days prior to surgery Significant hepatic, renal oder pulmonary disease Other concomitant surgical procedures

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: RIPC-CABG<br>Remote ischemic preconditioning (RIPC) protocol before coronary artery bypass surgery with blood cardioplegia for cardiac arrest (CABG) consists of 3 cycles of 5 minutes left upper arm ischemia by inflation of a blood pressure cuff to 200 mmHg and 5 minutes of reperfusion after induction of anesthesia before coronary artery bypass surgery. For myocardial molecular analyses, left ventricular biopsies are taken before induction of cardioplegic cardiac arrest and 5 to 10 Minutes after aortic unclamping during reperfusion of the myocardium. Blood samples are taken up to 72 hours postoperatively. | Procedure: Remote ischemic preconditioning (RIPC)<br>* 3 cycles of 5 min left upper arm ischemia by inflation of a blood pressure cuff to 200 mmHg and 5 min reperfusion. The applied anesthesia protocol avoids the use of propofol. Drugs: isoflurane+sufentanil anesthesia Anaesthesia is maintained by inhaled isoflurane in concentrations 0.7-0.8 % end-tidal with additional sufentanil injected during surgery, as required. In the CABG-arms, during extracorporal circulation patients receive isoflurane via a vaporizer incorporated in the extracorporeal gas supply in the same concentrations.<br>* Other names: Sufentanil, Sufenta, (R-30730);|
| Placebo Comparator: Control-CABG<br>Control group: Coronary artery bypass grafting without RIPC protocol | Procedure: Coronary artery bypass grafting (CABG) without remote ischemic preconditioning protocol<br>* The applied anesthesia protocol avoids the use of propofol. Drugs: isoflurane+sufentanil anesthesia Anaesthesia is maintained by inhaled isoflurane in concentrations 0.7-0.8 % end-tidal with additional sufentanil injected during surgery, as required. During extracorporal circulation patients receive isoflurane via a vaporizer incorporated in the extracorporeal gas supply in the same concentrations.<br>|
| Active Comparator: RIPC-OPCAB<br>Remote ischemic preconditioning (RIPC) protocol before Off-pump coronary artery bypass surgery (OPCAB) consists of 3 cycles of 5 minutes left upper arm ischemia by inflation of a blood pressure cuff to 200 mmHg and 5 minutes of reperfusion after induction of anesthesia before coronary artery bypass surgery. For myocardial molecular analyses, left ventricular biopsies are taken before first coronary artery incision and 5 to 10 Minutes after completion of the coronary anastomoses. Blood samples are taken up to 72 hours postoperatively. | Procedure: Remote ischemic preconditioning (RIPC)<br>* 3 cycles of 5 min left upper arm ischemia by inflation of a blood pressure cuff to 200 mmHg and 5 min reperfusion. The applied anesthesia protocol avoids the use of propofol. Drugs: isoflurane+sufentanil anesthesia Anaesthesia is maintained by inhaled isoflurane in concentrations 0.7-0.8 % end-tidal with additional sufentanil injected during surgery, as required. In the CABG-arms, during extracorporal circulation patients receive isoflurane via a vaporizer incorporated in the extracorporeal gas supply in the same concentrations.<br>* Other names: Sufentanil, Sufenta, (R-30730);|
| Placebo Comparator: Control-OPCAB<br>Control group: Off-pump Coronary artery bypass surgery without RIPC protocol | Procedure: Off-pump Coronary artery bypass surgery without remote ischemic preconditioning<br>* The applied anesthesia protocol avoids the use of propofol. Drugs: isoflurane+sufentanil anesthesia Anaesthesia is maintained by inhaled isoflurane in concentrations 0.7-0.8 % end-tidal with additional sufentanil injected during surgery, as required.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perioperative extent of myocardial injury as measured by cardiac troponin T serum release over 72 hours after coronary bypass surgery and its area under the curve (AUC). |  | 72 hours postoperatively after CABG surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality |  | 30 days and 1 year after coronary bypass surgery | 
| Major adverse cardiac and cerebrovascular events (MACCE) |  | 30 days and 1 year after coronary bypass surgery | 
| Myocardial infarction |  | 30 days and 1 year after coronary bypass surgery | 
| Renal function |  | 30 days and 1 year after coronary bypass surgery | 
| circulating microparticles after coronary bypass surgery |  | perioperatively, 3 months and 1 year after coronary bypass surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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remote ischemic preconditioning, coronary artery bypass grafting, myocardial injury