title: GLP-1 analogues for neuroprotection after out-of-hospital cardiac arrest: study protocol for a randomized controlled trial.
abstract: Attenuating the neurological damage occurring after out-of-hospital cardiac arrest is an ongoing research effort. This dual-centre study investigates the neuroprotective effects of the glucagon-like-peptide-1 analogue Exenatide administered within 4 hours from the return of spontaneous circulation to comatose patients resuscitated from out-of-hospital cardiac arrest.
  
  
  
  This pilot study will randomize a total of 120 unconscious patients with sustained return of spontaneous circulation after out-of-hospital cardiac arrest undergoing targeted temperature management in a blinded one-to-one fashion to a 6-hour and 15-minute infusion of either Exenatide or placebo. Patients are eligible for inclusion if resuscitated from cardiac arrest with randomization from 20 minutes to 240 minutes after return of spontaneous circulation. The co-primary endpoint is feasibility, defined as the initiation of treatment within the inclusion window in more than 90 % of participants, and efficacy, defined as the area under the neuron-specific enolase curve from 0 to 72 hours after admission. Secondary endpoints include all-cause mortality at 30 days and Cerebral Performance Category as well as a modified Rankin Score at 180 days. The study has been approved by the Danish National Board of Health and the local Ethics Committee and is monitored by Good Clinical Practice units. The study is currently enrolling.
  
  
  
  This paper presents the methods and planned statistical analyses used in the GLP-1 trial and aims to minimize bias and data-driven reporting of results.
  
  
  
  1) Danish National Board of Health, EudraCT 2013-004311-45. Registered on 25 March 2014. 2) Videnskabsetisk komité C, Region Hovedstaden, No. 45728. Registered on 29 January 2014. 3) Clinicaltrial.gov, NCT02442791 . Registered on 25 of January 2015.
authors.affiliation: Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. scwiberg@gmail.com.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wiberg
authors.affiliation: Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Hassager
authors.affiliation: Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jakob Hartvig
authors.initials: JH
authors.lastname: Thomsen
authors.affiliation: Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Frydland
authors.affiliation: Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Dan Eik
authors.initials: DE
authors.lastname: Høfsten
authors.affiliation: Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Engstrøm
authors.affiliation: Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Køber
authors.affiliation: Department of Anaesthesiology and Intensive care, Odense University Hospital, 5000, Odense C, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Schmidt
authors.affiliation: Department of Cardiology, Odense University Hospital, 5000, Odense C, Denmark.
authors.forename: Jacob Eifer
authors.initials: JE
authors.lastname: Møller
authors.affiliation: Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Kjaergaard
mesh_terms: D016887:Cardiopulmonary Resuscitation; D002561:Cerebrovascular Disorders / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D002985:Clinical Protocols; D003718:Denmark; D004185:Disability Evaluation; D004311:Double-Blind Method; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D006801:Humans; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D058687:Out-of-Hospital Cardiac Arrest / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D012107:Research Design; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014688:Venoms / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide
keywords: GLP-1 analogues; Neuroprotection; Out-of-hospital cardiac arrest