Direct Inhibition of δ-Protein Kinase C Enzyme to Limit Total Infarct Size in Acute MI - DELTA MI – Presented at ACC 2007
The goal of the trial was to evaluate treatment with the novel δ-protein kinase C inhibitor KAI-9803 compared with placebo among patients with ST-elevation myocardial infarction (MI) undergoing primary percutaneous coronary intervention (PCI).
Patients Enrolled: 154
Mean Follow Up: 6 months
Anterior ST-elevation MI, left anterior descending artery with occluded flow (TIMI flow grade 0 or 1), planned primary PCI
Patients were randomized 2:1 to KAI-9803 (n = 102) in one of four ascending doses (0.05, 0.5, 1.25, and 5.0 mg) or placebo (n = 52). Study drug was administered via two intracoronary injections, one prior to PCI and one post-PCI.
The median creatine kinase-myocardial band (CK-MB) area under the curve was consistent numerically, but nonsignificantly lower with KAI-9803 than with placebo at each of the dose groups (0.05 mg: 4001 vs. 4858 ng/ml; 0.5 mg: 5226 vs. 6934 ng/ml; 1.25 mg: 5740 vs. 7352 ng/ml; 5.0 mg: 6662 vs. 8230 ng/ml). Infarct size on SPECT at 14 days was numerically but nonsignificantly lower in the 0.5 mg groups and 1.25 mg groups than placebo (23% vs. 29.5% and 32.5% vs. 43.0%), but did not differ from placebo in the lowest dose group (25.5% vs. 33.5%) or the highest dose group (45.5% vs. 30.0%). Likewise, post-PCI TIMI myocardial perfusion grade 3 was more common in the KAI-9803 0.5 mg and 1.25 mg groups compared with placebo (72.2% vs. 53.8% and 69.6% vs. 45.4%), but did not differ from placebo in the low-dose group (60.0% vs. 72.7%) or the high-dose group (48.0% vs. 61.5%).
At 6-month follow-up, there was no difference in mortality or site-reported chronic heart failure. The frequency of serious adverse events was similar among the KAI-9803 and placebo groups. All patients received both injections of study medication.
Among patients with ST-elevation MI undergoing primary PCI, treatment with the novel δ-protein kinase C inhibitor KAI-9803 via intracoronary injection was associated with numerical but nonsignificantly lower post-PCI CK-MB release compared with placebo.
Limited therapies have been successful in reducing reperfusion injury. The present trial was a small, first-in-man dose-escalation study and not powered for full efficacy or safety evaluation. There were some signals of efficacy with less CK-MB release post-PCI and smaller infarct size, although none of these reductions was significant. There was no signal of a safety hazard, but a much larger study would be needed to fully assess safety.
Presented by Dr. Matthew T. Roe at the i2 Summit/American College of Cardiology Annual Scientific Session, New Orleans, LA, March 2007.
Clinical Topics: Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Vascular Medicine, Acute Heart Failure, Interventions and Imaging, Interventions and Vascular Medicine, Computed Tomography, Nuclear Imaging
Keywords: Myocardial Infarction, Reperfusion Injury, Follow-Up Studies, Tomography, Emission-Computed, Single-Photon, Creatine Kinase, MB Form, Heart Failure, Protein Kinase C, Percutaneous Coronary Intervention
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