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GLP-1 Analogs for Neuroprotection After Cardiac Arrest (GLIP1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02442791
Recruitment Status : Completed
First Posted : May 13, 2015
Last Update Posted : September 28, 2017
Sponsor:
Information provided by (Responsible Party):
Jesper Kjaergaard, Rigshospitalet, Denmark

Study Description
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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.

Condition or disease Intervention/treatment Phase
Cardiac Arrest Coma Drug: Byetta (Lilly, Exenatide) Other: 20% Human Albumin Not Applicable

Detailed Description:

In comatose patients resuscitated from out of hospital cardiac arrest, neurological injuries remain the leading cause of death. The in-hospital mortality is reported at 30-50%, and the total mortality, although improved substantially over the last decade, remain to be significant, in most countries up to 90%. The brain of a patient resuscitated after cardiac arrest (CA) may have suffered ischemia and when the spontaneous circulation is re-established, the subsequent reperfusion may cause further damage. Brain ischemia and the reperfusion injury lead to tissue degeneration and loss of neurological function, the extent dependent on duration and density of the insult. Temperature control and mild induced hypothermia (MIH) (33-36°C) mitigate this damage in the experimental setting and clinical trials have shown promising results in improving neurological function and survival. Recent large scale clinical trials however have investigated milder degree of hypothermia in this setting, which suggest a role for active neuroprotection outside of temperature management. Also recently, increased attention to the possible role of Glucagon-Like Peptide-1 (GLP-1) in neuroprotection has been raised, both in the context of ameliorating degenerative disease and in reducing inflammation on ischemic cerebral stroke.

Several experimental studies have shown that GLP-1 analogs has a beneficial effect in the treatment of various degenerative neurological diseases such as Alzheimer's disease and Parkinson's disease. GLP-1 analogs have been shown to reduce brain infarct size in mice after focal brain ischemia as well as to reduce heart infarct size in swine in a model of myocardial infarction.

Recent clinical testing in humans have demonstrated a benefit of GLP-1 infusion on myocardial infarct size and a larger salvage index in patients with myocardial infarction. The GLP-1 analogs were infused in acutely ill patients in many ways similar to cardiac arrest patients with no increased risk of adverse events.

This study is a double blinded randomized study seeking to evaluate the potential neuroprotective effects of GLP-1 analogs infused in comatose patients after out of hospital cardiac arrest.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: GLP-1 Analogs for Neuroprotection After Out-of-hospital Cardiac Arrest, a Randomized Clinical Trail
Study Start Date : June 2014
Actual Primary Completion Date : June 2016
Actual Study Completion Date : June 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Exenatide

Arms and Interventions
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Arm Intervention/treatment
Experimental: GLP-1

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)
See description of Arms
Other Name: Byetta

Other: 20% Human Albumin
See description of Arms
Placebo Comparator: Placebo

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
See description of Arms


Outcome Measures
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Primary Outcome Measures :
  1. Feasibility: Over 90% initiation of study drug infusion [ Time Frame: 4 hours from return of spontaneous circulation ]
  2. Efficacy assessed by Area under the Neuron-specific Enolase curve [ Time Frame: 72 hours from admission ]

Secondary Outcome Measures :
  1. Neurological prognostication [ Time Frame: Day 5 ]
    Blinded neurological evaluation by neurologist on "VAS-scale"

  2. Area under Neuron-specific Enolase curves (NSE) [ Time Frame: 48 hours ]
    Daily measurements of NSE values

  3. All cause mortality [ Time Frame: 180 days ]
    Vital status by end of study by registry based follow-up

  4. Cerebral status [ Time Frame: 30 days, 90 days and 180 days ]
    Telephone based assessment of Cerebral Performance Category and modified Rankin Scale.

  5. 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. [ Time Frame: 180 days ]
  6. Area under S100b curve [ Time Frame: 48 hours ]
    Daily measurements of S100b


Other Outcome Measures:
  1. Left Ventricular Ejection Fraction (LVEF) [ Time Frame: Day 5 or later ]
    LVEF on last in-hospital echocardiogram.

  2. EEG findings [ Time Frame: Day 3 to 5 ]
    Presence of EEG findings associated with poor prognosis.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • Conscious patients (obeying verbal commands)
  • Females of childbearing potential (unless a negative pregnancy test can rule out pregnancy within the inclusion window)
  • 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
  • Diabetic ketoacidosis,

  • Uncorrected blood glucose at admission < 2.5 mmol/l.

    • If the systolic blood pressure (SBP) is recovering during the inclusion window (220 minutes) the patient can be included.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02442791


Locations
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Denmark
Kardiologisk Afdeling, Rigshospitalet
Copenhagen, Denmark, DK-2100
Sponsors and Collaborators
Jesper Kjaergaard
Investigators
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Principal Investigator: Jesper Kjaergaard, MD., DMSc. Rigshospitalet, Denmark
More Information
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Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Jesper Kjaergaard, MD, DMSc, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT02442791    
Other Study ID Numbers: 2013-TTMPharma-001
First Posted: May 13, 2015    Key Record Dates
Last Update Posted: September 28, 2017
Last Verified: September 2017
Keywords provided by Jesper Kjaergaard, Rigshospitalet, Denmark:
Cardiac arrest
GLP-1
Neuroprotection
Additional relevant MeSH terms:
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Heart Arrest
Heart Diseases
Cardiovascular Diseases
Exenatide
Hypoglycemic Agents
 Physiological Effects of Drugs
Anti-Obesity Agents
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists