A randomized, double-blind, placebo-controlled study of the safety and efficacy of intravenous MCC-135 as an adjunct to primary percutaneous coronary intervention in patients with acute myocardial infarction: rationale and design of the evaluation of MCC-135 for left ventricular salvage in acute MI (EVOLVE) study.
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.
Jang
Ik-Kyung
IK
Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. ijang@partners.org
Pettigrew
Veronica
V
Picard
Michael H
MH
Kowey
Peter R
PR
Demmel
Valentin
V
Zile
Michael R
MR
Tatsuno
Jun
J
Wackers
Frans J Th
FJ
Hibberd
Mark
M
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D015906:Angioplasty, Balloon, Coronary; D001557:Benzenesulfonates / Q000008:administration & dosage*; D002118:Calcium / Q000378:metabolism*; D004311:Double-Blind Method; D004452:Echocardiography; D006801:Humans; D008297:Male; D008875:Middle Aged; D032342:Muscle Cells / Q000378:metabolism* / Q000473:pathology; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009336:Necrosis / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D010879:Piperazines / Q000008:administration & dosage*; D011859:Radiography; D015899:Tomography, Emission-Computed, Single-Photon; D016277:Ventricular Function, Left / Q000187:drug effects*
D001557:Benzenesulfonates; C434457:MCC 135; D010879:Piperazines; D002118:Calcium