Acute and Chronic Protective Effects of Peri-interventional Administration of Levosimendan in ST Elevation Myocardial Infarctions

Study Overview
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Brief Summary
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In the proposed project the investigators want to assess whether the approach of the post-conditioning by Levosimendan in patients with acute STEMI is safe and reproducible, can be used with a positive influence on the outcomes with respect to myocardial damage, cardiac left ventricular remodeling, myocardial function, the occurrence of cardiac events and quality of life.

Detailed Description
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An acute ST-elevation myocardial infarction (STEMI) is a severe disease that triggers an adverse remodeling, and served in progressive heart failure with a case fatality rate of 50% in 5 years. The opening of the occluded vessel is the first and most important therapy, the reperfusion improved both the function as well as the long-term survival. At the same time, experimental and clinical studies show, however, that this reperfusion self-reinforced damage of the myocardium. An additional Intervention in this trigger phase could not only reduce the acute damage, but long-term protective effects. Both effects could be an approach for the Calcium-Sensitizer Levosimendan in the animal model. So far, no clear effect on the remodeling and survive was demonstrated after myocardial infarction in the clinic. This could be mainly due to the delayed application in relation to the reperfusion and on the selection of suitable methods for the presentation of the effects on myocardial structure and function. In the proposed project the investigators want to assess whether the approach of the post-conditioning by Levosimendan in patients with acute STEMI is safe and reproducible, can be used with a positive influence on the outcomes with respect to myocardial damage, cardiac left ventricular remodeling, myocardial function, the occurrence of cardiac events and quality of life.

Official Title
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Acute and Chronic Protective Effects of Peri-interventional Administration of Levosimendan in ST Elevation Myocardial Infarctions

Conditions
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Myocardial Infarction, Outcome

Intervention / Treatment
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* Drug: Levosimendan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: STEMI of the anterior wall < 6 hrs capacity to Consent Exclusion Criteria: previous myocardial infarction or bypass surgery relevant vitium STEMI of the posterior wall any contraindications to MRI unstable hemodynamics (hypotension, catecholamine therapy, severe arrhythmia), -respiratory failure onset of symptoms more than 6 hours.

Ages Eligible for Study
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Minimum Age: 18 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo is given as a Bolus (instead of Bolus application of Levosimendan) over 10 min i.v., starting 10 min before recanalization. | Drug: Levosimendan<br>* In a prospective randomized setting, patients are included with an acute STEMI of the anterior wall. A bolus administration Levosimendan with/without following continuous infusion over 24 hours compared to a control group (placebo) will be examined. The initiation of therapy is carried out for 10 min. prior to reperfusion. The coronary Intervention is performed immediately after inclusion at the latest within 6 hours after the onset of symptoms. The administration of Levosimendan is based on a fixed schema: Bolus: 12 µg/kg over 10 min I. V., starting 10 min before recanalization and an addition of 0.1-0.2 µg/kg/min i. v. for 24 hours in the continuous infusion group.<br>|
| Active Comparator: Bolus Levosimendan<br>Levosimendan is given as Bolus (12 µg/kg over 10 min i.v.), starting 10 min before recanalization. | Drug: Levosimendan<br>* In a prospective randomized setting, patients are included with an acute STEMI of the anterior wall. A bolus administration Levosimendan with/without following continuous infusion over 24 hours compared to a control group (placebo) will be examined. The initiation of therapy is carried out for 10 min. prior to reperfusion. The coronary Intervention is performed immediately after inclusion at the latest within 6 hours after the onset of symptoms. The administration of Levosimendan is based on a fixed schema: Bolus: 12 µg/kg over 10 min I. V., starting 10 min before recanalization and an addition of 0.1-0.2 µg/kg/min i. v. for 24 hours in the continuous infusion group.<br>|
| Active Comparator: Bolus and infusion Levosimendan<br>Levosimendan is given as Bolus (12 µg/kg over 10 min i.v.), starting 10 min before recanalization and additionally as continuous infusion (0.1-0.2 µg/kg/min i. v. for 24 hours). | Drug: Levosimendan<br>* In a prospective randomized setting, patients are included with an acute STEMI of the anterior wall. A bolus administration Levosimendan with/without following continuous infusion over 24 hours compared to a control group (placebo) will be examined. The initiation of therapy is carried out for 10 min. prior to reperfusion. The coronary Intervention is performed immediately after inclusion at the latest within 6 hours after the onset of symptoms. The administration of Levosimendan is based on a fixed schema: Bolus: 12 µg/kg over 10 min I. V., starting 10 min before recanalization and an addition of 0.1-0.2 µg/kg/min i. v. for 24 hours in the continuous infusion group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of the increase in left ventricular end-diastolic volume index (LVEDVi) | echocardiography and MRI examinations (LVEDVi) and comparison between baseline and 12 months data | 12 months after coronary intervention due to the infarction | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Size of the acute myocardial damage due to the infarction | MRI examination (infarction area) and comparison between baseline and 12 months data | 12 months after coronary intervention due to the infarction | 
| Event-free survival | collection of data from the patient after 12 months about adverse events as myocardial infarction, stroke, revascularization and death | 12 months after coronary intervention due to the infarction | 
| functional changes (imaging) | echocardiography and MRI examinations about LV function | 12 months after coronary intervention due to the infarction | 
| structural changes | MRI examinations about fibrosis | 12 months after coronary intervention due to the infarction | 
| functional changes (spirometry) | changes of capacity by spirometry. | 12 months after coronary intervention due to the infarction |