Novel Drug Safe, Effective for Prevention of Peri-operative Cardiac Ischemia Reperfusion Injury

MIAMI BEACH, FLA.—A phase IIa study that examined the use of three different doses of a novel drug for the prevention of peri-operative cardiac ischemia-reperfusion injury suggests it is safe and efficacious at all doses.

These results support the basis for continuation of further study and the creation of a phase III study design, said Mitchell W. Krucoff, MD, of the Duke Clinical Research Institute, at TCT 2012.

CMX-2043

The prospective, randomized, multicenter, phase IIa Subjects Undergoing PCI and Perioperative Reperfusion Treatment (SUPPORT 1) trial  included 142 patients randomly assigned to receive an infusion of 0.8 mg/kg (n=36), 1.6 mg/kg (n=35) or 2.4 mg/kg (n=36) of CMX-2043 or  placebo (n=35) prior to PCI. All patients had stable coronary artery disease and were undergoing elective procedures with one or more stents. CMX-2043 is a cardio-protective drug candidate that combines Akt pathway-mediated cell survival effects and antioxidant activity in a single small molecule. The primary outcome was safety as measured by biomarkers of cardiac damage.

Compared with placebo, the 2.4mg/kg dose of the study drug was associated with the most statistically significant reduction in CK-MB (P=.05) and troponin T (P=.03) and a reduction in MI greater than three times the elevation of the upper limit of normal (P=.024).

“This is a very early-phase trial, but it is most important to note the serum marker elevations reported here, and what are categorized as statistically significant, may have no relevance to clinical outcomes — this was not the goal nor the intent of this trial,” Krucoff said.

Opportunity for new strategies

“The incidence and implications of periprocedural MI as documented by protein enzyme elevations is a controversy in our field,” he added. “PCI clearly does represent a human laboratory in which we have an opportunity known as ischemic distress to test chemical strategies for cytoprotection.

“In this regard, we can say there is no question that PCI produces apoptosis events, whatever the clinical relevance may be, and the selected proteins we tend to measure in reaching clinical circumstances, do represent myocellular necroses. There is a predicate at the center for testing drugs in this environment as cytoprotective strategies,” he said.