A Michael Lincoff1, Matthew Roe2, Philip Aylward3, John Galla4, Andrzej Rynkiewicz5, Victor Guetta6, Michael Zelizko7, Neal Kleiman8, Harvey White9, Ellen McErlean4, David Erlinge10, Mika Laine11, Jorge Manuel Dos Santos Ferreira12, Shaun Goodman13, Shamir Mehta14, Dan Atar15, Harry Suryapranata16, Svend Eggert Jensen17, Tamas Forster18, Antonio Fernandez-Ortiz19, Danny Schoors20, Peter Radke21, Guido Belli22, Danielle Brennan4, Gregory Bell23, Mitchell Krucoff2. 1. Cleveland Clinic Coordinating Center for Clinical Research (C5Research), Cleveland, OH, USA lincofa@ccf.org. 2. Duke Clinical Research Institute, Durham, NC, USA. 3. Flinders University and Medical Centre, Adelaide, Australia. 4. Cleveland Clinic Coordinating Center for Clinical Research (C5Research), Cleveland, OH, USA. 5. Department of Cardiology and Cardiosurgery, University of Warmia and Mazury, Olsztyn, Poland. 6. Heart Institute, Sheba Medical Center, Tel Hashomer, Israel. 7. Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. 8. Methodist DeBakey Heart & Vascular Center, Houston, TX, USA. 9. Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand. 10. Department of Cardiology, Lund University, Lund, Sweden. 11. Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland. 12. Department of Cardiology, Hospital Santa Cruz, Carnaxide, Portugal. 13. Canadian Heart Research Centre and St. Michael's HospitalUniversity of Toronto, Toronto, Ontario, Canada. 14. Department of Cardiology, Hamilton General Hospital Hamilton, Ontario, Canada. 15. Department of Cardiology B, Oslo University Hospital, Norway, and Institute of Clinical Sciences, University of Oslo, Oslo, Norway. 16. Department of Cardiology, Radboud University Nijmegen Medical Center, The Netherlands. 17. Department of Cardiology, Århus University Hospital, Aalborg, Denmark. 18. Medical Faculty, University of Szeged and Albert Szent-Gyorgyi Medical and Pharmaceutical Center, Szeged, Hungary. 19. Coronary Care Unit, Hospital Clinico San Carlos, Madrid, Spain. 20. Interventional Department, Universitair Ziekenhuis Brussel, Belgium. 21. Department of Cardiology, Angiology, Intensive Care Medicine, University of Schleswig Holstein, Lübeck, Germany. 22. Unita Operativa di Emodinamica e Cardiologia Invasiva Istitutio Clinico Humanitas, Milano, Italy. 23. KAI Phamaceuticals and Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Abstract
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. Published on behalf of the European Society of Cardiology. All rights reserved.
RCT Entities:
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. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Jie Zhang; Daniel Levy; Marko Oydanich; Claudio A Bravo; Seonghun Yoon; Dorothy E Vatner; Stephen F Vatner Journal: J Mol Cell Cardiol Date: 2018-05-22 Impact factor: 5.000
Authors: Gerd Heusch; Hans Erik Bøtker; Karin Przyklenk; Andrew Redington; Derek Yellon Journal: J Am Coll Cardiol Date: 2015-01-20 Impact factor: 24.094