Clinical trial NCT00324766: Levosimendan in Acute Heart Failure Following Acute Myocardial Infarction.
Official title: Safety and Efficacy of Levosimendan in Patients With Acute Myocardial Infarction Complicated by Symptomatic Left Ventricular Failure.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Myocardial Infarction
Heart Failure
Cardiogenic Shock
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
First posted: 2006-05-11
Enrollment: 61
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Efficacy: Changes in regional contractility measured as wall-motion score index, proBNP and clinical symptoms.
timeFrame: At 5 days
Secondary outcomes:
measure: Mace: Time to death, non-fatal myocardial infarction or revascularization during the first 6 weeks and 6 months.
timeFrame: 6 months
measure: Time to rehospitalisation for decompensated heart failure.
timeFrame: 6 months
measure: Days hospitalised/days in intensive/coronary care.
timeFrame: At discharge
measure: Changes in inflammation markers.
timeFrame: 1, 5 days, 6 weeks.
measure: Improvement in creatinine clearance.
timeFrame: 5 days
measure: Improvement of hemodynamic parameters.
timeFrame: 5 days
measure: Central venous oxygen saturation.
timeFrame: 1 day
measure: Total mortality.
timeFrame: 6 months
measure: Arrhythmias, hypotension, ischaemic episodes.
timeFrame: 5 days
measure: Change in proBNP
timeFrame: Baseline to day 5
measure: Change in clinical symptom score
timeFrame: Baseline to day 5
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Department of Cardiology, Ulleval University Hospital
Study officials:
affiliation: Department of Cardiology, Ulleval University Hospital
name: Trygve Husebye, MD,
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Cardiology, Ulleval University Hospital
name: Geir Ø Andersen, MD, PhD
role: STUDY_CHAIR
References:
citation: Langseth MS, Andersen GO, Husebye T, Arnesen H, Zucknick M, Solheim S, Eritsland J, Seljeflot I, Opstad TB, Helseth R. Neutrophil extracellular trap components and myocardial recovery in post-ischemic acute heart failure. PLoS One. 2020 Oct 29;15(10):e0241333. doi: 10.1371/journal.pone.0241333. eCollection 2020.
citation: Husebye T, Eritsland J, Arnesen H, Bjornerheim R, Mangschau A, Seljeflot I, Andersen GO. Association of interleukin 8 and myocardial recovery in patients with ST-elevation myocardial infarction complicated by acute heart failure. PLoS One. 2014 Nov 12;9(11):e112359. doi: 10.1371/journal.pone.0112359. eCollection 2014.
citation: Husebye T, Eritsland J, Muller C, Sandvik L, Arnesen H, Seljeflot I, Mangschau A, Bjornerheim R, Andersen GO. Levosimendan in acute heart failure following primary percutaneous coronary intervention-treated acute ST-elevation myocardial infarction. Results from the LEAF trial: a randomized, placebo-controlled study. Eur J Heart Fail. 2013 May;15(5):565-72. doi: 10.1093/eurjhf/hfs215. Epub 2013 Jan 2.