• Sebastian Wiberg, Christian Hassager, Henrik Schmidt, Thomsen Jakob Hartvig JH 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, Martin Frydland, Matias Greve Lindholm, Dan Eik Høfsten, Thomas Engstrøm, Lars Køber, Jacob Eifer Møller, and Jesper Kjaergaard.
• 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.
• Circulation. 2016 Dec 20; 134 (25): 2115-2124.

BackgroundIn-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.MethodsWe 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.ResultsThe 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.ConclusionsAcute 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.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT02442791.© 2016 American Heart Association, Inc.

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