title: Neuroprotective Effects of the Glucagon-Like Peptide-1 Analog Exenatide After Out-of-Hospital Cardiac Arrest: A Randomized Controlled Trial.
abstract: BACKGROUND
  In-hospital mortality in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA) is ≈50%. In OHCA patients, the leading cause of death is neurological injury secondary to ischemia and reperfusion. Glucagon-like peptide-1 analogs are approved for type 2 diabetes mellitus; preclinical and clinical data have suggested their organ-protective effects in patients with ischemia and reperfusion injury. The aim of this trial was to investigate the neuroprotective effects of the glucagon-like peptide-1 analog exenatide in resuscitated OHCA patients.
  
  
  METHODS
  We randomly assigned 120 consecutive comatose patients resuscitated from OHCA in a double-blind, 2-center trial. They were administered 17.4 μg exenatide (Byetta) or placebo over a 6-hour and 15-minute infusion, in addition to standardized intensive care including targeted temperature management. The coprimary end points were feasibility, defined as initiation of the study drug in >90% patients within 240 minutes of return of spontaneous circulation, and efficacy, defined as the geometric area under the neuron-specific enolase curve from 24 to 72 hours after admission. The main secondary end points included a composite end point of death and poor neurological function, defined as a Cerebral Performance Category score of 3 to 5 assessed at 30 and 180 days.
  
  
  RESULTS
  The study drug was initiated within 240 minutes of return of spontaneous circulation in 96% patients. The median blood glucose 8 hours after admission in patients receiving exenatide was lower than that in patients receiving placebo (5.8 [5.2-6.7] mmol/L versus 7.3 [6.2-8.7] mmol/L, P<0.0001). However, there were no significant differences in the area under the neuron-specific enolase curve, or a composite end point of death and poor neurological function between groups. Adverse events were rare with no significant difference between groups.
  
  
  CONCLUSIONS
  Acute administration of exenatide to comatose patients in the intensive care unit after OHCA is feasible and safe. Exenatide did not reduce neuron-specific enolase levels and did not significantly improve a composite end point of death and poor neurological function after 180 days.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT02442791.
authors.affiliation: From Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Denmark (S.W., C.H., J.H.T., M.F., M.G.L., D.E.H., T.E., L.K., J.K.); Department of Anaesthesiology and Intensive care, Odense University Hospital, Denmark (H.S.); and Department of Cardiology, Odense University Hospital, Denmark (J.E.M.). sebastian.christoph.wiberg@regionh.dk.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wiberg
authors.affiliation: From Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Denmark (S.W., C.H., J.H.T., M.F., M.G.L., D.E.H., T.E., L.K., J.K.); Department of Anaesthesiology and Intensive care, Odense University Hospital, Denmark (H.S.); and Department of Cardiology, Odense University Hospital, Denmark (J.E.M.).
authors.forename: Christian
authors.initials: C
authors.lastname: Hassager
authors.affiliation: From Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Denmark (S.W., C.H., J.H.T., M.F., M.G.L., D.E.H., T.E., L.K., J.K.); Department of Anaesthesiology and Intensive care, Odense University Hospital, Denmark (H.S.); and Department of Cardiology, Odense University Hospital, Denmark (J.E.M.).
authors.forename: Henrik
authors.initials: H
authors.lastname: Schmidt
authors.affiliation: From Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Denmark (S.W., C.H., J.H.T., M.F., M.G.L., D.E.H., T.E., L.K., J.K.); Department of Anaesthesiology and Intensive care, Odense University Hospital, Denmark (H.S.); and Department of Cardiology, Odense University Hospital, Denmark (J.E.M.).
authors.forename: Jakob Hartvig
authors.initials: JH
authors.lastname: Thomsen
authors.affiliation: From Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Denmark (S.W., C.H., J.H.T., M.F., M.G.L., D.E.H., T.E., L.K., J.K.); Department of Anaesthesiology and Intensive care, Odense University Hospital, Denmark (H.S.); and Department of Cardiology, Odense University Hospital, Denmark (J.E.M.).
authors.forename: Martin
authors.initials: M
authors.lastname: Frydland
authors.affiliation: From Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Denmark (S.W., C.H., J.H.T., M.F., M.G.L., D.E.H., T.E., L.K., J.K.); Department of Anaesthesiology and Intensive care, Odense University Hospital, Denmark (H.S.); and Department of Cardiology, Odense University Hospital, Denmark (J.E.M.).
authors.forename: Matias Greve
authors.initials: MG
authors.lastname: Lindholm
authors.affiliation: From Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Denmark (S.W., C.H., J.H.T., M.F., M.G.L., D.E.H., T.E., L.K., J.K.); Department of Anaesthesiology and Intensive care, Odense University Hospital, Denmark (H.S.); and Department of Cardiology, Odense University Hospital, Denmark (J.E.M.).
authors.forename: Dan Eik
authors.initials: DE
authors.lastname: Høfsten
authors.affiliation: From Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Denmark (S.W., C.H., J.H.T., M.F., M.G.L., D.E.H., T.E., L.K., J.K.); Department of Anaesthesiology and Intensive care, Odense University Hospital, Denmark (H.S.); and Department of Cardiology, Odense University Hospital, Denmark (J.E.M.).
authors.forename: Thomas
authors.initials: T
authors.lastname: Engstrøm
authors.affiliation: From Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Denmark (S.W., C.H., J.H.T., M.F., M.G.L., D.E.H., T.E., L.K., J.K.); Department of Anaesthesiology and Intensive care, Odense University Hospital, Denmark (H.S.); and Department of Cardiology, Odense University Hospital, Denmark (J.E.M.).
authors.forename: Lars
authors.initials: L
authors.lastname: Køber
authors.affiliation: From Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Denmark (S.W., C.H., J.H.T., M.F., M.G.L., D.E.H., T.E., L.K., J.K.); Department of Anaesthesiology and Intensive care, Odense University Hospital, Denmark (H.S.); and Department of Cardiology, Odense University Hospital, Denmark (J.E.M.).
authors.forename: Jacob Eifer
authors.initials: JE
authors.lastname: Møller
authors.affiliation: From Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Denmark (S.W., C.H., J.H.T., M.F., M.G.L., D.E.H., T.E., L.K., J.K.); Department of Anaesthesiology and Intensive care, Odense University Hospital, Denmark (H.S.); and Department of Cardiology, Odense University Hospital, Denmark (J.E.M.).
authors.forename: Jesper
authors.initials: J
authors.lastname: Kjaergaard
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D004311:Double-Blind Method; D000077270:Exenatide; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000627:therapeutic use; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D058687:Out-of-Hospital Cardiac Arrest / Q000188:drug therapy* / Q000401:mortality; D010455:Peptides / Q000627:therapeutic use*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D015990:Placebo Effect; D015996:Survival Rate; D016896:Treatment Outcome; D014688:Venoms / Q000627:therapeutic use*; D014693:Ventricular Fibrillation / Q000209:etiology
chemical_list: D001786:Blood Glucose; D018696:Neuroprotective Agents; D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D010751:Phosphopyruvate Hydratase
keywords: glucagon-like peptide-1 analogs; neuroprotection; out-of-hospital cardiac arrest