NCT02442791

Brief Summary

Experimental studies and previous clinical trials suggest neuroprotective effects of GLP-1 analogs in various degenerative neurological diseases, and in hypoxic brain injuries in experimental designs. This study is designed as a safety and feasibility study with patients randomized 1:1 to receive GLP-1 analogs immediately after hospital admission after out of hospital cardiac arrest.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
120

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Jun 2014

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2014

Completed
8 months until next milestone

First Submitted

Initial submission to the registry

January 25, 2015

Completed
4 months until next milestone

First Posted

Study publicly available on registry

May 13, 2015

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2016

Completed
Last Updated

September 28, 2017

Status Verified

September 1, 2017

Enrollment Period

2 years

First QC Date

January 25, 2015

Last Update Submit

September 26, 2017

Conditions

Cardiac ArrestComa

Keywords

Cardiac arrestGLP-1Neuroprotection

Outcome Measures

Primary Outcomes (2)

  • Feasibility: Over 90% initiation of study drug infusion

    4 hours from return of spontaneous circulation

  • Efficacy assessed by Area under the Neuron-specific Enolase curve

    72 hours from admission

Secondary Outcomes (6)

  • Neurological prognostication

    Day 5

  • Area under Neuron-specific Enolase curves (NSE)

    48 hours

  • All cause mortality

    180 days

  • Cerebral status

    30 days, 90 days and 180 days

  • Safety: Cumulated incidence of serious adverse events related to study drug: death, need for mechanical hemodynamic support, hypoglycaemia < 3.0 mmol/l, pancreatitis (S-amylase > 3 UNL), need for renal replacement therapy in the first 3 days.

    180 days

  • +1 more secondary outcomes

Other Outcomes (2)

  • Left Ventricular Ejection Fraction (LVEF)

    Day 5 or later

  • EEG findings

    Day 3 to 5

Study Arms (2)

GLP-1

EXPERIMENTAL

Half of the participants will receive the study drug, that will be given as follows: 250 mL isotonic sodium chloride added 1.5 mL of 20% Human Albumin added 25 microg Byetta (Lilly, Exenatide). The study drug infusion is initiated as soon as possible at rate of 72ml/hour (0.12 μg/min) for 15 min (set volume at 18 ml), followed by 26ml/hour (0.043 μg/min) to be continued for 6 hours (set volume at 156 ml). This concludes the pharmacological intervention.

Drug: Byetta (Lilly, Exenatide)Other: 20% Human Albumin

Placebo

PLACEBO COMPARATOR

Half of the participants will receive placebo, that will be given as follows: 250 mL isotonic sodium chloride added 1.5 mL of 20% Human Albumin. The placebo infusion is administered exactly the same way as the study drug infusion.

Other: 20% Human Albumin

Interventions

Byetta (Lilly, Exenatide)DRUG

See description of Arms

Also known as: Byetta
GLP-1
20% Human AlbuminOTHER

See description of Arms

GLP-1Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Out of hospital cardiac arrest (OHCA) of presumed cardiac cause
  • Sustained return of spontaneous circulation (ROSC)
  • Unconsciousness (GCS \<8 (Glasgow coma scale)) (patients not able to obey verbal commands)
  • Sustained ROSC (Sustained ROSC: Sustained ROSC is when chest compressions have been not required for 20 consecutive minutes and signs of circulation persist)

You may not qualify if:

  • Conscious patients (obeying verbal commands)
  • In-hospital cardiac arrest (IHCA)
  • OHCA of presumed non-cardiac cause, e.g. after trauma or dissection/rupture of major artery OR Cardiac arrest caused by initial hypoxia (i.e. drowning, suffocation, hanging).
  • Known bleeding diathesis (medically induced coagulopathy (e.g. warfarin, clopidogrel) does not exclude the patient).
  • Suspected or confirmed acute intracranial bleeding
  • Suspected or confirmed acute stroke
  • Unwitnessed asystole
  • Known limitations in therapy and Do Not Resuscitate-order
  • Known disease making 180 days survival unlikely
  • Known pre-arrest cerebral performance category 3 or 4
  • \>4 hours (240 minutes) from ROSC to screening
  • Systolic blood pressure \<80 mm Hg in spite of fluid loading/vasopressor and/or inotropic medication/intra aortic balloon pump/axial flow device\*
  • Temperature on admission \<30°C.
  • Known allergy to GLP-1 analogs, including Exenatide
  • Known pancreatitis
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Kardiologisk Afdeling, Rigshospitalet

Copenhagen, DK-2100, Denmark

Location

Related Publications (4)

  • Wiberg S, Hassager C, Schmidt H, Thomsen JH, Frydland M, Lindholm MG, Hofsten DE, Engstrom T, Kober L, Moller JE, Kjaergaard J. Neuroprotective Effects of the Glucagon-Like Peptide-1 Analog Exenatide After Out-of-Hospital Cardiac Arrest: A Randomized Controlled Trial. Circulation. 2016 Dec 20;134(25):2115-2124. doi: 10.1161/CIRCULATIONAHA.116.024088. Epub 2016 Nov 12.

    PMID: 27838646RESULT

  • Toftgaard Pedersen A, Kjaergaard J, Hassager C, Frydland M, Hartvig Thomsen J, Klein A, Schmidt H, Moller JE, Wiberg S. Association between inflammatory markers and survival in comatose, resuscitated out-of-hospital cardiac arrest patients. Scand Cardiovasc J. 2022 Dec;56(1):85-90. doi: 10.1080/14017431.2022.2074093.

    PMID: 35546563DERIVED

  • Wiberg S, Kjaergaard J, Schmidt H, Thomsen JH, Frydland M, Winther-Jensen M, Lindholm MG, Hofsten DE, Engstrom T, Kober L, Moller JE, Hassager C. The Glucagon-Like Peptide-1 Analog Exenatide Increases Blood Glucose Clearance, Lactate Clearance, and Heart Rate in Comatose Patients After Out-of-Hospital Cardiac Arrest. Crit Care Med. 2018 Feb;46(2):e118-e125. doi: 10.1097/CCM.0000000000002814.

    PMID: 29189347DERIVED

  • Wiberg S, Hassager C, Thomsen JH, Frydland M, Hofsten DE, Engstrom T, Kober L, Schmidt H, Moller JE, Kjaergaard J. GLP-1 analogues for neuroprotection after out-of-hospital cardiac arrest: study protocol for a randomized controlled trial. Trials. 2016 Jun 30;17(1):304. doi: 10.1186/s13063-016-1421-2.

    PMID: 27363489DERIVED

MeSH Terms

Conditions

Heart ArrestComa

Interventions

ExenatideSerum Albumin, Human

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular DiseasesUnconsciousnessConsciousness DisordersNeurobehavioral ManifestationsNeurologic ManifestationsNervous System DiseasesSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

PeptidesAmino Acids, Peptides, and ProteinsVenomsComplex MixturesToxins, BiologicalBiological FactorsSerum AlbuminAlbuminsProteinsBlood Proteins

Study Officials

  • Jesper Kjaergaard, MD., DMSc.

    Rigshospitalet, Denmark

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
MD, DMSc

Study Record Dates

First Submitted

January 25, 2015

First Posted

May 13, 2015

Study Start

June 1, 2014

Primary Completion

June 1, 2016

Study Completion

June 1, 2016

Last Updated

September 28, 2017

Record last verified: 2017-09

Locations

DK(1)