title: Effect of intravenous TRO40303 as an adjunct to primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: MITOCARE study results.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Cardiology B, Oslo University Hospital Ullevål, and Faculty of Medicine, University of Oslo, Oslo, Norway dan.atar@online.no.
authors.forename: Dan
authors.initials: D
authors.lastname: Atar
authors.affiliation: Department of Clinical Physiology, Lund University, Skåne University Hospital, Lund, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Arheden
authors.affiliation: Université Paris Est Val de Marne, Créteil, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Berdeaux
authors.affiliation: Assistance Publique Hôpitaux de Marseille, Hôpital La Timone, Marseille, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Bonnet
authors.affiliation: Department of Clinical Physiology, Lund University, Skåne University Hospital, Lund, Sweden.
authors.forename: Marcus
authors.initials: M
authors.lastname: Carlsson
authors.affiliation: Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Clemmensen
authors.affiliation: Trophos SA, Luminy Biotech Enterprises, Marseille, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Cuvier
authors.affiliation: Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Danchin
authors.affiliation: Assistance Publique Hôpitaux de Paris, Hôpital Henri Mondor, Créteil, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Dubois-Randé
authors.affiliation: Department of Clinical Physiology, Lund University, Skåne University Hospital, Lund, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Engblom
authors.affiliation: Department of Cardiology, Lund University, Lund, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Erlinge
authors.affiliation: Firalis SAS, Huningue, France.
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Firat
authors.affiliation: Department of Cardiology B, Oslo University Hospital Ullevål, and Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Sigrun
authors.initials: S
authors.lastname: Halvorsen
authors.affiliation: Department of Cardiology B, Odense University Hospital, Odense, Denmark.
authors.forename: Henrik Steen
authors.initials: HS
authors.lastname: Hansen
authors.affiliation: Trophos SA, Luminy Biotech Enterprises, Marseille, France.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Hauke
authors.affiliation: Department of Clinical Physiology, Lund University, Skåne University Hospital, Lund, Sweden.
authors.forename: Einar
authors.initials: E
authors.lastname: Heiberg
authors.affiliation: Department of Cardiology, Lund University, Lund, Sweden.
authors.forename: Sasha
authors.initials: S
authors.lastname: Koul
authors.affiliation: Department of Cardiology, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Alf-Inge
authors.initials: AI
authors.lastname: Larsen
authors.affiliation: Assistance Publique Hôpitaux de Paris, Hôpital Henri Mondor, Créteil, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Le Corvoisier
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Jan Erik
authors.initials: JE
authors.lastname: Nordrehaug
authors.affiliation: Department of Cardiology, Hospital Nord, Marseille, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Paganelli
authors.affiliation: Trophos SA, Luminy Biotech Enterprises, Marseille, France.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Pruss
authors.affiliation: Clinical Research Unit, Lariboisière Hospital, Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Rousseau
authors.affiliation: Trophos SA, Luminy Biotech Enterprises, Marseille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Schaller
authors.affiliation: Mobile Health, Paris, France.
authors.forename: Giles
authors.initials: G
authors.lastname: Sonou
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Vegard
authors.initials: V
authors.lastname: Tuseth
authors.affiliation: Trophos SA, Luminy Biotech Enterprises, Marseille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Veys
authors.affiliation: Clinical Research Unit, Lariboisière Hospital, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Vicaut
authors.affiliation: Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Svend Eggert
authors.initials: SE
authors.lastname: Jensen
mesh_terms: D000800:Angioplasty, Balloon / Q000379:methods*; D019540:Area Under Curve; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy; D054059:Coronary Occlusion / Q000473:pathology / Q000628:therapy; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors; D000083162:Mitochondrial Permeability Transition Pore; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D010091:Oximes / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D012632:Secosteroids / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D002316:Cardiotonic Agents; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010091:Oximes; D012632:Secosteroids; C549911:3,5-seco-4-norcholestan-5-one oxime-3-ol
keywords: CMR; Cardiac reperfusion injury; Infarct size; Mitochondria; Primary PCI; STEMI