As a consequence of acute
ischemia and reperfusion in patients with acute
ST elevation myocardial infarction,
calcium overload inside myocytes not only affects myocardial contraction, relaxation, and myocyte recovery following reperfusion, but also may be related to myocyte
necrosis and fatal
arrhythmia.
MCC-135 is the first in a new class of agents that reduce intracellular
calcium overload. Pre-clinical and early clinical studies yielded promising results for patients with
ST elevation myocardial infarction. The Evaluation of
MCC-135 for Left Ventricular Salvage in Acute MI (EVOLVE) study is a Phase 2a, multicenter, randomized, double-blind, placebo-controlled clinical trial of 2 new doses of
MCC-135 (4.5 mg/kg/48 hours and 9.0 mg/kg/48 hours) as adjunct
therapy for preservation of left ventricular function and reduction of
infarct size in patients undergoing primary
percutaneous coronary intervention (PCI) for electrocardiographically moderate-large
ST elevation myocardial infarction. The primary endpoint will be left ventricular ejection fraction on Day 5 post
myocardial infarction as determined by single photon emission computed tomography (SPECT). Secondary endpoints will include SPECT and echocardiographic assessments, serum cardiac
markers, clinical outcomes, and safety measures at specific time points through Day 30 post
myocardial infarction. Follow-up clinical and safety assessments will be continued until Day 180. The rationale, design, and methods of the EVOLVE study are described in this paper, along with 2 sub-studies, involving a comparison of pre- and post-PCI measurements with either SPECT or echocardiography, to examine myocardial salvage and the time course of changes in
myocardial infarction size and left ventricular function. MINIABSTRACT: The Evaluation of
MCC-135 for Left Ventricular Salvage in Acute MI (EVOLVE) study is a Phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial of two doses of
MCC-135, first in a new class of agents that reduce intracellular
calcium overload, as adjunct
therapy for preservation of left ventricular function and reduction of
infarct size in patients with moderate-large
STEMI undergoing primary PCI. The rationale, design, and methods of the EVOLVE study, along with two sub-studies, are described in this paper.