AIMS: Delcasertib is a selective inhibitor of delta-protein kinase C (delta-PKC), which reduced infarct size during ischaemia/reperfusion in animal models and diminished myocardial necrosis and improved reperfusion in a pilot study during primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI). METHODS AND RESULTS: A multicentre, double-blind trial was performed in patients presenting within 6 h and undergoing primary PCI for anterior (the primary analysis cohort, n = 1010 patients) or inferior (an exploratory cohort, capped at 166 patients) STEMI. Patients with anterior STEMI were randomized to placebo or one of three doses of delcasertib (50, 150, or 450 mg/h) by intravenous infusion initiated before PCI and continued for ∼2.5 h. There were no differences between treatment groups in the primary efficacy endpoint of infarct size measured by creatine kinase MB fraction area under the curve (AUC) (median 5156, 5043, 4419, and 5253 ng h/mL in the placebo, delcasertib 50, 150, and 450 mg/mL groups, respectively) in the anterior STEMI cohort. No treatment-related differences were seen in secondary endpoints of infarct size, electrocardiographic ST-segment recovery AUC or time to stable ST recovery, or left ventricular ejection fraction at 3 months. No differences in rates of adjudicated clinical endpoints (death, heart failure, or serious ventricular arrhythmias) were observed. CONCLUSIONS: Selective inhibition of delta-PKC with intravenous infusion of delcasertib during PCI for acute STEMI in a population of patients treated according to contemporary standard of care did not reduce biomarkers of myocardial injury.

Canadian Heart Research Centre and St Michael's HospitalUniversity of Toronto Toronto Ontario Canada

Cleveland Clinic Coordinating Center for Clinical Research Cleveland OH USA

Coronary Care Unit Hospital Clinico San Carlos Madrid Spain

Department of Cardiology and Cardiosurgery University of Warmia and Mazury Olsztyn Poland

Department of Cardiology Angiology Intensive Care Medicine University of Schleswig Holstein Lübeck Germany

Department of Cardiology Århus University Hospital Aalborg Denmark

Department of Cardiology B Oslo University Hospital Norway and Institute of Clinical Sciences University of Oslo Oslo Norway

Department of Cardiology Hamilton General Hospital Hamilton Ontario Canada

Department of Cardiology Hospital Santa Cruz Carnaxide Portugal

Department of Cardiology Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Cardiology Lund University Lund Sweden

Department of Cardiology Radboud University Nijmegen Medical Center The Netherlands

Division of Cardiology Helsinki University Central Hospital Helsinki Finland

Duke Clinical Research Institute Durham NC USA

Flinders University and Medical Centre Adelaide Australia

Green Lane Cardiovascular Service Auckland City Hospital Auckland New Zealand

Heart Institute Sheba Medical Center Tel Hashomer Israel

Interventional Department Universitair Ziekenhuis Brussel Belgium

KAI Phamaceuticals and Department of Medicine University of California San Francisco San Francisco CA USA

Medical Faculty University of Szeged and Albert Szent Gyorgyi Medical and Pharmaceutical Center Szeged Hungary

Methodist DeBakey Heart and Vascular Center Houston TX USA

Unita Operativa di Emodinamica e Cardiologia Invasiva Istitutio Clinico Humanitas Milano Italy

Eur Heart J. 2014 Oct 1;35(37):2504-6. doi: 10.1093/eurheartj/ehu200. PubMed

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ClinicalTrials.gov
NCT00785954