title: Inhibition of delta-protein kinase C by delcasertib as an adjunct to primary percutaneous coronary intervention for acute anterior ST-segment elevation myocardial infarction: results of the PROTECTION AMI Randomized Controlled Trial.
abstract: OBJECTIVE
  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).
  
  
  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.
authors.affiliation: Cleveland Clinic Coordinating Center for Clinical Research (C5Research), Cleveland, OH, USA lincofa@ccf.org.
authors.forename: A Michael
authors.initials: AM
authors.lastname: Lincoff
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Roe
authors.affiliation: Flinders University and Medical Centre, Adelaide, Australia.
authors.forename: Philip
authors.initials: P
authors.lastname: Aylward
authors.affiliation: Cleveland Clinic Coordinating Center for Clinical Research (C5Research), Cleveland, OH, USA.
authors.forename: John
authors.initials: J
authors.lastname: Galla
authors.affiliation: Department of Cardiology and Cardiosurgery, University of Warmia and Mazury, Olsztyn, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Rynkiewicz
authors.affiliation: Heart Institute, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Victor
authors.initials: V
authors.lastname: Guetta
authors.affiliation: Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Michael
authors.initials: M
authors.lastname: Zelizko
authors.affiliation: Methodist DeBakey Heart & Vascular Center, Houston, TX, USA.
authors.forename: Neal
authors.initials: N
authors.lastname: Kleiman
authors.affiliation: Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand.
authors.forename: Harvey
authors.initials: H
authors.lastname: White
authors.affiliation: Cleveland Clinic Coordinating Center for Clinical Research (C5Research), Cleveland, OH, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: McErlean
authors.affiliation: Department of Cardiology, Lund University, Lund, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Erlinge
authors.affiliation: Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Laine
authors.affiliation: Department of Cardiology, Hospital Santa Cruz, Carnaxide, Portugal.
authors.forename: Jorge Manuel
authors.initials: JM
authors.lastname: Dos Santos Ferreira
authors.affiliation: Canadian Heart Research Centre and St. Michael's HospitalUniversity of Toronto, Toronto, Ontario, Canada.
authors.forename: Shaun
authors.initials: S
authors.lastname: Goodman
authors.affiliation: Department of Cardiology, Hamilton General Hospital Hamilton, Ontario, Canada.
authors.forename: Shamir
authors.initials: S
authors.lastname: Mehta
authors.affiliation: Department of Cardiology B, Oslo University Hospital, Norway, and Institute of Clinical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Dan
authors.initials: D
authors.lastname: Atar
authors.affiliation: Department of Cardiology, Radboud University Nijmegen Medical Center, The Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: Suryapranata
authors.affiliation: Department of Cardiology, Århus University Hospital, Aalborg, Denmark.
authors.forename: Svend Eggert
authors.initials: SE
authors.lastname: Jensen
authors.affiliation: Medical Faculty, University of Szeged and Albert Szent-Gyorgyi Medical and Pharmaceutical Center, Szeged, Hungary.
authors.forename: Tamas
authors.initials: T
authors.lastname: Forster
authors.affiliation: Coronary Care Unit, Hospital Clinico San Carlos, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Fernandez-Ortiz
authors.affiliation: Interventional Department, Universitair Ziekenhuis Brussel, Belgium.
authors.forename: Danny
authors.initials: D
authors.lastname: Schoors
authors.affiliation: Department of Cardiology, Angiology, Intensive Care Medicine, University of Schleswig Holstein, Lübeck, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Radke
authors.affiliation: Unita Operativa di Emodinamica e Cardiologia Invasiva Istitutio Clinico Humanitas, Milano, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Belli
authors.affiliation: Cleveland Clinic Coordinating Center for Clinical Research (C5Research), Cleveland, OH, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Brennan
authors.affiliation: KAI Phamaceuticals and Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Bell
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Krucoff
mesh_terms: D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D052279:Creatine Kinase, MB Form / Q000378:metabolism; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000628:therapy*; D010455:Peptides / Q000008:administration & dosage*; D062645:Percutaneous Coronary Intervention / Q000379:methods*; D010865:Pilot Projects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D016896:Treatment Outcome; D019210:Troponin I / Q000378:metabolism
chemical_list: D015415:Biomarkers; C527142:KAI 9803; D010455:Peptides; D047428:Protein Kinase Inhibitors; D019210:Troponin I; D052279:Creatine Kinase, MB Form
keywords: Myocardial; Myocardial infarction; Pharmacology; Reperfusion; Stents; Stunning