Neuroprotective Effects of the Glucagon-Like Peptide-1 Analog Exenatide After Out-of-Hospital Cardiac Arrest: A Randomized Controlled Trial
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Neuroprotective Effects of the Glucagon-Like Peptide-1 Analog Exenatide After Out-of-Hospital Cardiac Arrest : A Randomized Controlled Trial. / Wiberg, Sebastian; Hassager, Christian; Schmidt, Henrik; Thomsen, Jakob Hartvig; Frydland, Martin; Lindholm, Matias Greve; Hoefsten, Dan Eik; Engstrøm, Thomas; Køber, Lars; Møller, Jacob Eifer; Kjaergaard, Jesper.
I: Circulation, Bind 134, Nr. 25, 20.12.2016, s. 2115-2124.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Neuroprotective Effects of the Glucagon-Like Peptide-1 Analog Exenatide After Out-of-Hospital Cardiac Arrest
T2 - A Randomized Controlled Trial
AU - Wiberg, Sebastian
AU - Hassager, Christian
AU - Schmidt, Henrik
AU - Thomsen, Jakob Hartvig
AU - Frydland, Martin
AU - Lindholm, Matias Greve
AU - Hoefsten, Dan Eik
AU - Engstrøm, Thomas
AU - Køber, Lars
AU - Møller, Jacob Eifer
AU - Kjaergaard, Jesper
N1 - © 2016 American Heart Association, Inc.
PY - 2016/12/20
Y1 - 2016/12/20
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Blood Glucose
KW - Double-Blind Method
KW - Female
KW - Glucagon-Like Peptide 1
KW - Hospital Mortality
KW - Humans
KW - Male
KW - Middle Aged
KW - Neuroprotective Agents
KW - Out-of-Hospital Cardiac Arrest
KW - Peptides
KW - Phosphopyruvate Hydratase
KW - Placebo Effect
KW - Survival Rate
KW - Treatment Outcome
KW - Venoms
KW - Ventricular Fibrillation
KW - Journal Article
KW - Multicenter Study
KW - Randomized Controlled Trial
U2 - 10.1161/CIRCULATIONAHA.116.024088
DO - 10.1161/CIRCULATIONAHA.116.024088
M3 - Journal article
C2 - 27838646
VL - 134
SP - 2115
EP - 2124
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 25
ER -
ID: 177340042