Effect of intravenous TRO40303 as an adjunct to primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: MITOCARE study results.

Abstract

AIM:

The MITOCARE study evaluated the efficacy and safety of TRO40303 for the reduction of reperfusion injury in patients undergoing revascularization for ST-elevation myocardial infarction (STEMI).

METHODS:

Patients presenting with STEMI within 6 h of the onset of pain randomly received TRO40303 (n = 83) or placebo (n = 80) via i.v. bolus injection prior to balloon inflation during primary percutaneous coronary intervention in a double-blind manner. The primary endpoint was infarct size expressed as area under the curve (AUC) for creatine kinase (CK) and for troponin I (TnI) over 3 days. Secondary endpoints included measures of infarct size using cardiac magnetic resonance (CMR) and safety outcomes.

RESULTS:

The median pain-to-balloon time was 180 min for both groups, and the median (mean) door-to-balloon time was 60 (38) min for all sites. Infarct size, as measured by CK and TnI AUCs at 3 days, was not significantly different between treatment groups. There were no significant differences in the CMR-assessed myocardial salvage index (1-infarct size/myocardium at risk) (mean 52 vs. 58% with placebo, P = 0.1000), mean CMR-assessed infarct size (21.9 g vs. 20.0 g, or 17 vs. 15% of LV-mass) or left ventricular ejection fraction (LVEF) (46 vs. 48%), or in the mean 30-day echocardiographic LVEF (51.5 vs. 52.2%) between TRO40303 and placebo. A greater number of adjudicated safety events occurred in the TRO40303 group for unexplained reasons.

CONCLUSION:

This study in STEMI patients treated with contemporary mechanical revascularization principles did not show any effect of TRO40303 in limiting reperfusion injury of the ischaemic myocardium.

• Authors: Dan Atar, Håkan Arheden, Alain Berdeaux, Jean-Louis Bonnet, Marcus Carlsson, Peter Clemmensen, Valérie Cuvier, Nicolas Danchin, Jean-Luc Dubois-Randé, Henrik Engblom, David Erlinge, Hüseyin Firat, Sigrun Halvorsen, Henrik Steen Hansen, Wilfried Hauke, Einar Heiberg, Sasha Koul, Alf-Inge Larsen, Philippe Le Corvoisier, Jan Erik Nordrehaug, Franck Paganelli, Rebecca M Pruss, Hélène Rousseau, Sophie Schaller, Giles Sonou, Vegard Tuseth, Julien Veys, Eric Vicaut, Svend Eggert Jensen
• Journal: European heart journal (Eur Heart J) Vol. 36 Issue 2 Pg. 112-9 (Jan 07 2015) ISSN: 1522-9645 [Electronic] England
• PMID: 25179768 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: [email protected].

Chemical References

• Cardiotonic Agents
• Mitochondrial Membrane Transport Proteins
• Mitochondrial Permeability Transition Pore
• Oximes
• Secosteroids
• 3,5-seco-4-norcholestan-5-one oxime-3-ol

Topics

• Angioplasty, Balloon (methods)
• Area Under Curve
• Cardiotonic Agents (administration & dosage, adverse effects)
• Combined Modality Therapy
• Coronary Occlusion (pathology, therapy)
• Double-Blind Method
• Female
• Humans
• Magnetic Resonance Angiography
• Male
• Middle Aged
• Mitochondrial Membrane Transport Proteins (antagonists & inhibitors)
• Mitochondrial Permeability Transition Pore
• Myocardial Infarction (pathology, therapy)
• Myocardial Reperfusion Injury (pathology, prevention & control)
• Oximes (administration & dosage, adverse effects)
• Prospective Studies
• Secosteroids (administration & dosage, adverse effects)
• Treatment Outcome