Developed as a potential new treatment to mitigate ischemic reperfusion injury and its subsequent negative effects on the body, TRO40303 has been found to be insufficient in reducing such injuries in patients undergoing revascularization for ST-elevation myocardial infarction (STEMI), according to results from the MITOCARE trial released Sept. 1 at ESC Congress 2014 and simultaneously published in the European Heart Journal.
Led by Dan Atar, MD, FACC, Department of Cardiology, Oslo University Hospital Ullevål, University of Oslo, Norway, the trial sought to test the human efficacy of the drug, as it had been shown to reduce infarct size in animal models and human cells. Between October 2011 and September 2013, Atar and his colleagues conducted a prospective, multicenter, randomized, double-blind, placebo-controlled, phase IIa, proof-of-concept in 10 clinical trial centers in four European countries, targeting a population of 163 that included patients greater than 18 years of age with a first-time STEMI.
Patients presenting with STEMI within six hours of feeling pain randomly received TRO40303 or a placebo via intravenous bolus injection prior to balloon inflation during primary percutaneous coronary intervention (PCI) in a double-blind manner. The primary endpoint was whether the infarct size expressed as area under the curve for creatine kinase (CK) and for troponin I (TnI) over three days.
Clocking a median pain-to-balloon time marked at 180 minutes for both groups, and a median door-to balloon time of 60 minutes for all sites, results showed that infarct size, as measured by CK and TnI area under the curve at three days, was not significantly different between treatment groups, with no significant differences in cardiac magnetic resonance (CMR)-assessed myocardial salvage index (1-infarct size/myocardium at risk) (mean 52 percent vs. 58 percent with placebo, p=0.1000), mean CMR-assessed infarct size (21.9 g vs. 20.0 g, or 17 percent vs. 15 percent of left ventricular-mass), left ventricular ejection fraction (LVEF)(46 percent vs. 48 percent), or in the mean 30-day echocardiographic LVEF (51.5 percent vs. 52.2 percent) between RO40303 and the placebo. For unexplained reasons, a greater number of adjudicated safety events occurred in the group treated with TRO40303.
Ultimately, Atar and his team conclude that further research is needed to provide additional insight into the nature of reperfusion therapy.
Keywords: Myocardial Infarction, Reperfusion Injury, Creatine Kinase, Troponin I, Stroke Volume, Pain, Magnetic Resonance Spectroscopy, Angioplasty, Balloon, Coronary
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