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Circulation. 2016 Dec 20;134(25):2115-2124. Epub 2016 Nov 12.

Neuroprotective Effects of the Glucagon-Like Peptide-1 Analog Exenatide After Out-of-Hospital Cardiac Arrest: A Randomized Controlled Trial.

Author information

1
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.
2
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.).

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.

CLINICAL TRIAL REGISTRATION:

URL: http://www.clinicaltrials.gov. Unique identifier: NCT02442791.

KEYWORDS:

glucagon-like peptide-1 analogs; neuroprotection; out-of-hospital cardiac arrest

[Indexed for MEDLINE]

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