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

Eur Heart J. 2015 Jan 7;36(2):112-9. doi: 10.1093/eurheartj/ehu331. Epub 2014 Sep 1.

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.

Keywords: CMR; Cardiac reperfusion injury; Infarct size; Mitochondria; Primary PCI; STEMI.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Cardiotonic Agents
  • Mitochondrial Membrane Transport Proteins
  • Oximes
  • Secosteroids
  • mitochondrial permeability transition pore
  • 3,5-seco-4-norcholestan-5-one oxime-3-ol