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

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 2016;36(2):112-9

PMID: 25179768

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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.

Address: Department of Cardiology B, Oslo University Hospital Ullevål, and Faculty of Medicine, University of Oslo, Oslo, Norway [email protected].; Department of Clinical Physiology, Lund University, Skåne University Hospital, Lund, Sweden.; Université Paris Est Val de Marne, Créteil, France.; Assistance Publique Hôpitaux de Marseille, Hôpital La Timone, Marseille, France.; Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.; Trophos SA, Luminy Biotech Enterprises, Marseille, France.; Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.; Assistance Publique Hôpitaux de Paris, Hôpital Henri Mondor, Créteil, France.; Department of Cardiology, Lund University, Lund, Sweden.; Firalis SAS, Huningue, France.; Department of Cardiology B, Oslo University Hospital Ullevål, and Faculty of Medicine, University of Oslo, Oslo, Norway.; Department of Cardiology B, Odense University Hospital, Odense, Denmark.; Department of Cardiology, Stavanger University Hospital, Stavanger, Norway.; Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Cardiology, Hospital Nord, Marseille, France.; Clinical Research Unit, Lariboisière Hospital, Paris, France.; Mobile Health, Paris, France.; Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.

DOI: 10.1093/eurheartj/ehu331