Levosimendan in Acute Heart Failure Following Acute Myocardial Infarction.

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and efficacy of a 24 hour infusion with levosimendan in patients with acute myocardial infarction and heart failure after acute percutaneous coronary intervention (PCI) treatment.

Detailed Description
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Double blind placebo-controlled study with parallel groups in patients with acute PCI treated myocardial infarction complicated with decompensated heart failure. The study include a prospectively defined subgroup of patients in cardiogenic shock. Treating acute myocardial infarction with PCI restores blood flow, but decreased contractility remains for hours and days due to stunned myocardium. Levosimendan has both inotropic and vasodilatory effects which could support the failing heart after treating the acute myocardial infarction with PCI and may improve myocardial stunning and decrease pro-inflammatory cytokines. Levosimendan could improve myocardial contractility, symptoms and outcome without adverse effects. The aims of the study are to investigate whether a 24 hour infusion with levosimendan could improve regional contractility measured by echocardiography, improve BNP levels, reduce the levels of pro-inflammatory cytokines and improve symptoms in patients with acute decompensated heart failure during the first 24 hours after acute PCI.

Official Title
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Safety and Efficacy of Levosimendan in Patients With Acute Myocardial Infarction Complicated by Symptomatic Left Ventricular Failure.

Conditions
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Myocardial Infarction, Heart Failure, Cardiogenic Shock

Intervention / Treatment
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* Drug: levosimendan
* Drug: placebo,


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute ST-elevation myocardial infarction subject to acute PCI or non-ST elevation myocardial infarction subject to PCI within 72 hours after start of chest pain and: Revascularization by PCI, Signs of decreased wall-motion in at least 3 of 16 segments of the left ventricle Dyspnoea at rest and one of the following: pulmonary edema, pulmonary congestion,need for CPAP or ventilator, need for IC diuretics or oliguria. Subgroup of patients in cardiogenic shock: Systolic BP below 90 after 1 hour of volume therapy. Exclusion Criteria: Age below 20 years Heart rate above 120 bpm Septic shock ARDS Creatinine >450 micromol/l Hepatic impairment Significant mechanical outlet obstruction Allergy against study drug medication Anaemia (Hb <8 g/dl) Pregnancy

Ages Eligible for Study
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Minimum Age: 20 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: 1<br>levosimendan | Drug: levosimendan<br>* 1 h infusion, 0.2 microgs/kg/min, 24 h infusion,0.1 microgs/kg/min<br>* Other names: Simdax;|
| Placebo Comparator: 2<br>Placebo, 1 h infusion, 0.2 microgs/kg/min, 24 h infusion,0.1 microgs/kg/min | Drug: placebo,<br>* 24 h, infusion<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Changes in regional contractility measured as wall-motion score index, proBNP and clinical symptoms. | Changes in regional contractility (WMSI) measured by echo is the primary endpoint in the study and the sample size calculation is based on expected differenced in WMSI from baseline to day 5 between groups. | At 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mace: Time to death, non-fatal myocardial infarction or revascularization during the first 6 weeks and 6 months. |  | 6 months | 
| Time to rehospitalisation for decompensated heart failure. |  | 6 months | 
| Days hospitalised/days in intensive/coronary care. |  | At discharge | 
| Changes in inflammation markers. |  | 1, 5 days, 6 weeks. | 
| Improvement in creatinine clearance. |  | 5 days | 
| Improvement of hemodynamic parameters. |  | 5 days | 
| Central venous oxygen saturation. |  | 1 day | 
| Total mortality. |  | 6 months | 
| Arrhythmias, hypotension, ischaemic episodes. |  | 5 days | 
| Change in proBNP |  | Baseline to day 5 | 
| Change in clinical symptom score |  | Baseline to day 5 |