Evaluation of a Local Preconditioning Effect in Patients Undergoing Cardiac Surgery

Study Overview
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Brief Summary
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The aim of the study is to analyze the potential of pressure controlled intermittent coronary sinus occlusion (PICSO) to prevent/reverse the ischemic burden as well as reperfusion injury. To achieve insight into the clinical significance of this local preconditioning effect, global hemodynamics, cardiac performance and clinical outcome in the first 30 days will be related to the ability of this intervention to protect the myocardium in elective surgical procedures, ameliorating cellular decay and preserving the microcirculation therefore improving graft flow, reducing enzyme leakage and finally improving myocardial performance.

Detailed Description
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Patients undergoing elective coronary artery bypass graft (CABG) will be enrolled in this study. A computerized randomization process is used to obtain similar distributions within each group. Stratification will be done by the severity of coronary artery disease, age and sex. Routine blood sampling will be performed the day before surgery as well as a transthoracic echocardiography (TTE) study to determine ventricular volumes and valvular function. A modified Minnesota quality of Life questionnaire will be assessed and these data will be compared with 30 days outcome data screened in an outpatient environment. A 12 lead electrocardiogram will be obtained. To assess eligibility and to assure grouping (stratification & randomization) patients will be scored using the additive EuroSCORE. Pre-, intra-, and postoperative (up to 72 hrs) measurements of myocardial enzyme leakage will be performed using standard diagnostic procedures (cardiac troponin T, CK-MB, and total creatine kinase), as well as serial electrocardiograms and echocardiograms. Perioperative infarction will be assessed as the development of new persistent regional wall motion abnormalities in echocardiography together with electrocardiographic alterations and CK-MB increases and new Q-wave PMI. Sequential cytokine analyses (IL-1, IL-6, IL-8, IL-10, IL-17, VEGF and TNF- alpha ) preoperatively, at the beginning of the operation, the beginning of ECC and 6,24 h and 30 days postop. Serial quantification of global and regional wall motion will be recorded using TEE measurements during surgery.

Official Title
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EASY-TRIAL: Evaluation of a Local Preconditioning Effect in Patients Undergoing Cardiac Surgery

Conditions
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Heart Disease, Coronary Artery Bypass Graft Triple Vessel

Intervention / Treatment
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* Device: PICSO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients of either sex and between 18 and 85 years of age scheduled for surgery without severe confounding disease will be asked to participate in the study. Written informed consent will be obtained in eligible patients. Exclusion Criteria: Patients with unstable angina pectoris and/or myocardial infarction within the last 30 days, as well as persons with planned concomitant valvular interventions will be excluded. Patients with malignoma, severe hepatic, renal and pulmonary disease will also be excluded

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PICSO<br>PICSO (pressure controlled intermittent coronary sinus occlusion), a special coronary sinus catheter will be introduced after induction of anaesthesia until going on bypass. | Device: PICSO<br>* PICSO (pressure controlled intermittent coronary sinus occlusion) will be used in the pre ECC period. The procedure of PICSO will be performed in analogy to retrograde cardioplegia.<br>* Other names: PICSO, Miracor medical Systems, Austria;|
| No Intervention: Control<br>normal procedure of preparing Bypass grafts. Equivalent time before going on Bypass is determined as control period | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in enzyme leakage measured by AUC. | Enzyme leakage (Troponin T, CK-MB) will be measured preoperatively, at the beginning of the operation, the beginning of ECC at the time of reperfusion the arrival on the ICU and 6,12,24,48 and 72 hours postop and the area under the curve will be calculated (AUC until 72 hours). Study Hypotheses: PICSO reduces troponin T leakage about 30 % measured by AUC until 72h in comparison to controls. PICSO improves 30d and long-term outcome | 72 hours postop | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined endpoint of major adverse cardiovascular events (MACE) and mortality after 30 days. |  | 30 days | 
| N-terminales pro brain natriuretic peptide (NT-pro BNP) values at 1 day pre-surgery as well as 30d and 6 months post-operative |  | 30 days | 
| Pre-operative (1d) as well as post-operative (6, 12, 24, 48, 72 h, 30d) C-reactive protein (CRP) measurements |  | 30 days |