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

Myocardial Infarction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03022877
• Other study ID #: Levo-STEMI
• Status: Withdrawn
• Phase: N/A
• Start date: June 2017
• Est. completion date: December 2018

Study information

• Verified date: October 2022
• Source: RWTH Aachen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction
• Outcome
• ST Elevation Myocardial Infarction

Intervention

Drug:
• Levosimendan
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
RWTH Aachen University

References & Publications (7)

Brooks GC, Lee BK, Rao R, Lin F, Morin DP, Zweibel SL, Buxton AE, Pletcher MJ, Vittinghoff E, Olgin JE; PREDICTS Investigators. Predicting Persistent Left Ventricular Dysfunction Following Myocardial Infarction: The PREDICTS Study. J Am Coll Cardiol. 2016 Mar 15;67(10):1186-1196. doi: 10.1016/j.jacc.2015.12.042. — View Citation

du Toit EF, Smith W, Muller C, Strijdom H, Stouthammer B, Woodiwiss AJ, Norton GR, Lochner A. Myocardial susceptibility to ischemic-reperfusion injury in a prediabetic model of dietary-induced obesity. Am J Physiol Heart Circ Physiol. 2008 May;294(5):H233 — View Citation

Hein M, Roehl AB, Baumert JH, Scherer K, Steendijk P, Rossaint R. Anti-ischemic effects of inotropic agents in experimental right ventricular infarction. Acta Anaesthesiol Scand. 2009 Aug;53(7):941-8. doi: 10.1111/j.1399-6576.2009.01994.x. Epub 2009 May 6 — View Citation

Kin H, Zhao ZQ, Sun HY, Wang NP, Corvera JS, Halkos ME, Kerendi F, Guyton RA, Vinten-Johansen J. Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion. Cardiovasc Res. 2004 Apr 1;62(1): — View Citation

Kloner RA, Jennings RB. Consequences of brief ischemia: stunning, preconditioning, and their clinical implications: part 2. Circulation. 2001 Dec 18;104(25):3158-67. Review. — View Citation

Qarawani D, Cohen A, Nahir M, Hasin Y. Facilitation of left ventricular function recovery post percutaneous coronary intervention by levosimendan. Int J Cardiol. 2013 Sep 20;168(1):237-42. doi: 10.1016/j.ijcard.2012.09.088. Epub 2012 Oct 11. — View Citation

Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med. 2007 Sep 13;357(11):1121-35. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	functional changes (imaging)	echocardiography and MRI examinations about LV function	12 months after coronary intervention due to the infarction
Secondary	structural changes	MRI examinations about fibrosis	12 months after coronary intervention due to the infarction
Secondary	functional changes (spirometry)	changes of capacity by spirometry.	12 months after coronary intervention due to the infarction