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GLP-1 and Hyperoxia for Organ Protection in Heart Surgery (GLORIOUS)

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ClinicalTrials.gov Identifier: NCT02673931
Recruitment Status : Recruiting
First Posted : February 4, 2016
Last Update Posted : April 17, 2018
Sponsor:
Information provided by (Responsible Party):
Lars Køber, Rigshospitalet, Denmark

Brief Summary:

Patients undergoing open heart surgery are at risk of suffering damage to the heart, brain and kidneys.

This study is designed as a 2-by-2 randomized clinical trial with the purpose of investigating the organ protective effects of the glucagon-like-peptide-1 (GLP-1) agonist Exenatide versus placebo and restrictive versus liberal oxygenation during weaning from cardio-pulmonary bypass.


Condition or disease Intervention/treatment Phase
Coronary Disease Shock, Cardiogenic Renal Failure Stroke Brain Injury Aortic Valve Disease Drug: Byetta (Lilly, Exenatide) Drug: Conoxia (AGA, oxygen) Drug: 20% Human Albumin Not Applicable

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1080 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy of Glucagon-like-peptide-1 Agonists and Restrictive vs. Liberal FiO2 in Patients Undergoing Coronary Artery Bypass Grafting or Aortic Valve Replacement - a 2-by-2 Factorial Designed, Randomized Clinical Study
Study Start Date : February 2016
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Surgery

Arm Intervention/treatment
Experimental: GLP-1

270 patients will be randomized to GLP-1, that will be administered as follows:

248.5 mL of isotonic sodium chloride added 1.5 mL of 20% human albumin added 25 microg Byetta (Lilly, Exenatide).

The study drug infusion is initiated immediately before open heart surgery and ended after 6 hours and 15 minutes. A set dose of 17.4 microg will be given.

Drug: Byetta (Lilly, Exenatide)
See description of arms
Other Name: GLP-1 agonist

Placebo Comparator: Placebo

20% Human Albumin is given as placebo. 270 patients will be randomized to placebo, that will be administered as follows:

248.5 mL of isotonic sodium chloride added 1.5 mL of 20% human albumin.

The placebo infusion is initiated immediately before open heart surgery and ended after 6 hours and 15 minutes at the same rate as the study drug.

Drug: 20% Human Albumin
Other Name: Albumin

Experimental: Restrictive Oxygenation

The intervention is FiO2 of 50%, given as 'Conoxia (AGA, oxygen)'. 270 patients will be randomized to a FiO2 of 50% as long as the arterial O2 saturation (Sa02) remains above 91% during cardiopulmonary bypass, when weaning from and the following hour after weaning from cardiopulmonary bypass. The oxygenation strategy is discontinued and the patient is treated at the discretion of the attending physician after

  1. a maximum of 1 hours of intervention or
  2. the patient is slid from the operating table to a hospital bed for transfer to the intensive care unit, whichever comes first.
Drug: Conoxia (AGA, oxygen)
See description arms
Other Name: Oxygen

Active Comparator: Liberal Oxygenation

The intervention is a FiO2 of 100%, given as 'Conoxia (AGA, oxygen)'. 270 patients will be randomized to a FiO2 of 100% during cardiopulmonary bypass, when weaning from and the following hour after weaning from cardiopulmonary bypass. The oxygenation strategy is discontinued and the patient is treated at the discretion of the attending physician after

  1. a maximum of 1 hours of intervention or
  2. the patient is slid from the operating table to a hospital bed for transfer to the intensive care unit, whichever comes first.
Drug: Conoxia (AGA, oxygen)
See description arms
Other Name: Oxygen




Primary Outcome Measures :
  1. The presence of a co-primary end-point [ Time Frame: 24 months ]
    1. Death from any cause or
    2. Any of the following adverse events

      1. Renal failure requiring any type of renal replacement therapy
      2. Stroke, defined as persisting (>24 hours) of any neurological sign or symptom of neurological dysfunction as determined by the treating physician based on available clinical information or CT-scan
      3. New onset/worsening heart failure defined as need for mechanical circulatory support at the ICU, inability to close the sternotomy due to post-surgical hemodynamic instability and/or persistent (> 48 hours from initiation of first surgical procedure after randomization) need for inotropic hemodynamic support. In addition admission for heart failure during follow-up following discharge from the index admission.


Secondary Outcome Measures :
  1. Time in days to the occurrence of individual end-points [ Time Frame: 24 months ]
    1. Time to death from any cause, or
    2. Time to death or stroke, or
    3. Time to death or renal dysfunction requiring dialysis, or
    4. Time to death or new hospitalization for heart failure during follow-up following discharge from the index admission, or
    5. Time to death or new onset/worsening in-hospital heart failure.

  2. Incidence of adverse events [ Time Frame: 12 months ]

    The rates of any of the adverse events:

    1. Surgical site infections with prolonged need (>48 h) for antibiotics, surgical intervention and/or endocarditis within 6 months of surgery, or
    2. Doubling of S-creatinine or decreased urine output <0.5ml/kg/h for 12 h or more at any timepoint during index admission, or
    3. Reduction of left ventricular ejection fraction (LVEF) of 50% (relative) compared to baseline at any time point during index admission, or
    4. Reoperation for bleeding, or
    5. Reoperation for any cause, or
    6. Post surgery myocardial infarction (MI) (Type 5 MI according to the Third International definition of Myocardial Infarction.), or
    7. Readmission for cardiovascular causes within 12 months of index surgery.

  3. Change in Cerebral Performance Category (CPC) [ Time Frame: 24 months ]
    Change from baseline in CPC-score

  4. Change in modified Rankin Scale (mRS) [ Time Frame: 24 months ]
    Change from baseline in mRS

  5. Change in self perceived function "two simple questions" [ Time Frame: 6 months ]
    'Two simple questions' at 6 months follow-up.



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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:

  • Before any study-specific procedure, including assessments for screening, the appropriate written informed consent must be obtained.
  • ≥ 18 years of age at the time of signing informed consent.
  • Ischemic heart disease requiring coronary artery bypass grafting (multi-vessel coronary artery disease or coronary anatomy not suitable for percutaneous coronary intervention) and/or aortic valve disease scheduled for aortic valve replacement, irrespective of other concomitant valve surgery.

Exclusion Criteria:

  • Active treatment with GLP-1 agonists
  • Obstructive hypertrophic cardiomyopathy, active myocarditis, constrictive pericarditis, untreated hypothyroidism or hyperthyroidism or history of or active acute pancreatitis.
  • Acute (i.e. off hours, within hours surgery), Sub-acute surgery (i.e. the following days) are eligible.
  • Known allergy towards Exenatide/Byetta or albumin (vehicle).
  • On the urgent waiting list for a heart transplant (UNOS category 1A or 1B, or equivalent). Patients on the non-urgent waiting list for a heart transplant (UNOS category 2 or 7, or equivalent) are eligible for inclusion in the study.
  • Recipient of any major organ transplant (e.g. lung, liver, heart)
  • Receiving or has received cytotoxic or cytostatic chemotherapy and/or radiation therapy for treatment of a malignancy within 6 month before randomization or clinical evidence of current malignancy, with the following exceptions: basal or squamous cell carcinoma of the skin, cervical intraepithelial neoplasia, prostate cancer (if stable localized disease, with a life expectancy of > 2.5 years in the opinion of the investigator)
  • Currently enrolled in, or at least 30 days not yet elapsed since ending participation in other investigational drug trial(s) for the treatment of diabetes or malignant obesity investigating the use of GLP-1 agonists or receiving other investigational agent(s). Concomitant participation in other non-pharmacological trials is not an exclusion criterion.
  • Recent (within 3 months) history of alcohol or illicit drug abuse disorder, based on self-report.
  • Pregnant, based on investigator evaluation (e.g., positive human chorionic gonadotropin test) or currently breast feeding.
  • Any condition (e.g., psychiatric illness) or situation that, in the investigator's opinion, could put the subject at significant risk, confound the study results, or interfere significantly with the subject's participation in the study.
  • Previous participation in the trial.

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): NCT02673931


Contacts
Contact: Lars Køber, MD, DMSc Lars.Koeber@regionh.dk
Contact: Jesper Kjaergaard, MD, DMSc jesper.kjaergaard.05@regionh.dk

Locations
Denmark
Rigshospitalet - Copenhagen University Hospital Recruiting
Copenhagen, Denmark, 2100
Contact: Jens C Nilsson, MD, PhD       Jens.Christian.Nilsson@regionh.dk   
Sponsors and Collaborators
Rigshospitalet, Denmark
Investigators
Study Director: Peter Skov Olsen, MD, DMSc Rigshospitalet, Denmark
Principal Investigator: Jens Christian Nilsson, MD, PhD Rigshospitalet, Denmark
Study Chair: Lars Køber, MD, DMSc Rigshospitalet, Denmark

Responsible Party: Lars Køber, MD, Professor, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT02673931     History of Changes
Other Study ID Numbers: HJE-PHARMA-001
First Posted: February 4, 2016    Key Record Dates
Last Update Posted: April 17, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Lars Køber, Rigshospitalet, Denmark:
Open Heart Surgery
Organ protection

Additional relevant MeSH terms:
Brain Injuries
Renal Insufficiency
Coronary Disease
Coronary Artery Disease
Shock, Cardiogenic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Kidney Diseases
Urologic Diseases
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Myocardial Infarction
Shock
Pathologic Processes
Exenatide
Glucagon-Like Peptide 1
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists