Protection During Cardiac Surgery.

Study Overview
=================
Brief Summary
-----------------
This trial investigates whether a multimodal cardioprotection per-surgery therapeutic strategy could reduce myocardial injury in patients undergoing cardiac surgery compared to traditional management. The primary endpoint is the AUC (area under the curve) of the hypersensitive troponin I. Blood samples will be collected during the 72 hours following the aortic cross-unclamping. This trial is a French, multicenter, randomized, single-blinded and controlled trial. 210 patients will be enrolled with a clinical follow-up during 30 days.

Official Title
-----------------
Protection During Cardiac Surgery.

Conditions
-----------------
Thoracic Surgery, Cardiopulmonary Bypass

Intervention / Treatment
-----------------
* Other: multimodal cardioprotection strategy
* Other: standard anesthetic procedure


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age > 18 years old Aortic valve surgery (aortic valve replacement associated or not with coronary artery bypass graft, Bentall surgery or Tirone David surgery) Signed informed consent Exclusion Criteria: Emergency surgery Redo surgery Patient treated with Nicorandil, repaglinid or sulfonylurea 48 hours prior to surgery Low cardiac output requiring catecholamine infusion or circulatory assistance prior to surgery Severe renal failure: dialysis or glomerular filtration rate < 30 mL/min Severe liver failure (spontaneous INR >2) Severe respiratory insufficiency (VEMS <40% of predicted value) Contra-indication to sevoflurane and propofol Myocardial infarction < 7 days Severe upper limb arterial disease Heparin-induced thrombopenia Active infection under antibiotic treatment Any other surgery combined with the aortic valve surgery: myotomia of Morrow (hypertrophic myocardiopathy), treatment of heart rhythm disorder, inter-atrial communication closure, mitral valve replacement, tricuspid valve replacement, pulmonary valve replacement. Pregnant women Currently participating in another trial which may interfere with ProCCard results Not benefiting from a social insurance or similar system Patient under legal protection

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multimodal cardioprotection therapeutic strategy<br> | Other: multimodal cardioprotection strategy<br>* Multimodal cardioprotection therapeutic strategy will include (1) remote ischemic preconditioning, (2) volatile anesthetic sevoflurane-induced preconditioning, (3) blood glucose control every 30 minutes during cardiac surgery, (4) temporary respiratory acidosis prior to the aortic cross-unclamping and (5) gradual restoration of blood flow after aortic cross-unclamping (gentle reperfusion).<br>|
| Active Comparator: Traditional anesthetic and therapeutic<br>standard anesthetic procedure No intervention (Control). | Other: standard anesthetic procedure<br>* standard anesthetic procedure will include: anesthesia under propofol throughout the cardiac surgery, blood glucose control every 60 minutes, arterial pH maintained at 7.40, theoric blood flow restored at the earliest after aortic cross-unclamping.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) of Hypersensitive Troponin I | Area under the plasma concentration versus time curve (AUC) of Hypersensitive Troponin I determined for each patient with the serial measurement from of troponin I assays. | at 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events incidence during the first 30 days following surgery of the multimodal cardioprotection strategy | Adverse events will include death, myocardial infarction, heart failure,arrhythmia requiring medical therapy, neurological disorder such as stroke,respiratory insufficiency, any infectious event, major bleeding requiring transfusion of ≥ 5 U packed red blood cells or surgical intervention or surgical complication | 30 days | 
| Troponin I serum peak value | Highest serum value recorded for each patient within 72 hours | 72 hours | 
| Troponin I serum value | Serum value recorded for each patient within 24 hours | 24 hours | 
| Length of mechanical ventilation |  | 30 days | 
| Length of stay in intensive care unit (ICU) |  | 30 days | 
| Length of stay in hospital |  | 30 days | 
| Index Gravity Score (IGS II, the scoring system measuring the severity of disease for patients admitted to ICU) | Index Gravity Score provides an estimate of the risk of death: the higher the score is, the higher the risk to die is. The maximum score is 163. The Index Gravity Score includes 17 variables: 12 physiology variables, age, type of admission (scheduled surgical, unscheduled surgical, or medical), and three underlying disease variables (acquired immunodeficiency syndrome, metastatic cancer, and hematologic malignancy). | 24 hours | 
| Number of participants with catecholaminergic support |  | baseline and 30 days | 
| Dose of catecholaminergic support |  | baseline and 30 days | 
| 3-level version of EQ-5D (EQ-5D-3L) health status score (quality of life score) | The 3-level version of EQ-5D consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS).It comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results into a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. The VAS can be used as a quantitative measure of health outcome that reflects the patient's own judgement. | Baseline and 30 days | 
| number of death |  | 30 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Myocardial injury, Ischemia reperfusion, cardiac surgery, cardioprotection