Neuroprotective Effects of the Glucagon-Like Peptide-1 Analog Exenatide After Out-of-Hospital Cardiac Arrest: A Randomized Controlled Trial.
Wiberg, Sebastian MD; Hassager, Christian MD, DMSc; Schmidt, Henrik MD, DMSc; Thomsen, Jakob Hartvig MD; Frydland, Martin MD; Lindholm, Matias Greve MD, PhD; Hofsten, Dan Eik MD, PhD; Engstrom, Thomas MD, PhD, DMSc; Kober, Lars MD, DMSc; Moller, Jacob Eifer MD, PhD, DMSc; Kjaergaard, Jesper MD, PhD, DMSc
134(25):2115-2124, December 20, 2016.
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Background: In-hospital mortality in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA) is [almost equal to]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 [mu]g 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.
Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02442791.
(C) 2016 by the American College of Cardiology Foundation and the American Heart Association, Inc.