GLP-1 and Hyperoxia for Organ Protection in Heart Surgery

NCT02673931 | Active Not Recruiting DMC

• 1 other identifier: HJE-PHARMA-001
• Study Type: interventional
• Target: 1,400
• Locations: 1 country
• Sites: 1

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.

Conditions

Coronary Disease; Shock, Cardiogenic; Renal Failure; Stroke; Brain Injury; Aortic Valve Disease

Keywords

Open Heart Surgery; Organ protection

Outcome Measures

Primary Outcomes (1)

• Time in days to the first occurring of the following co-primary end-points throughout the follow-up period

  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.

  Minimum 12 months

Secondary Outcomes (2)

• Time in days to the occurrence of individual end-points throughout the follow-up period

  Minimum 12 months

• Incidence of serious adverse events

  12 months

Other Outcomes (1)

• Time in days to the first occurring primary end-point within 90 days

  90 days

Study Arms (4)

GLP-1

EXPERIMENTAL

700 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)

Placebo

PLACEBO COMPARATOR

20% Human Albumin is given as placebo. 700 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

Restrictive Oxygenation

EXPERIMENTAL

The intervention is FiO2 of 50%, given as 'Conoxia (AGA, oxygen)'. 700 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)

Liberal Oxygenation

ACTIVE COMPARATOR

The intervention is a FiO2 of 100%, given as 'Conoxia (AGA, oxygen)'. 700 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)

Interventions

Byetta (Lilly, Exenatide) DRUG

See description of arms

Also known as: GLP-1 agonist

GLP-1

Conoxia (AGA, oxygen) DRUG

See description arms

Also known as: Oxygen

Liberal Oxygenation; Restrictive Oxygenation

20% Human Albumin DRUG

Also known as: Albumin

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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)
• 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.

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (1)

Rigshospitalet - Copenhagen University Hospital

Copenhagen, 2100, Denmark

Location

Related Publications (3)

• Wiberg S, Moller CH, Kjaergaard J, Mikkelsen AD, Sorensen HM, Kunkel JB, Olsen PS, Hofsten DE, Ravn J, Ravn H, Boesgaard S, Hassager C, Kober L, Nilsson JC. Restrictive versus liberal oxygenation in patients undergoing cardiopulmonary bypass-assisted heart surgery: a randomised controlled trial. Br J Anaesth. 2025 Dec;135(6):1618-1625. doi: 10.1016/j.bja.2025.08.005. Epub 2025 Sep 19.

  PMID: 40975689 DERIVED

• Kjaergaard J, Moller CH, Wiberg S, Mikkelsen AD, Moller-Sorensen H, Ravn HB, Ravn J, Olsen PS, Hofsten DE, Boesgaard S, Kober L, Nilsson JC, Hassager C. Efficacy of the Glucagon-Like Peptide-1 Agonist Exenatide in Patients Undergoing CABG or Aortic Valve Replacement: A Randomized Double-Blind Clinical Trial. Circ Cardiovasc Interv. 2025 May;18(5):e014961. doi: 10.1161/CIRCINTERVENTIONS.124.014961. Epub 2025 Apr 23.

  PMID: 40265262 DERIVED

• Wiberg S, Kjaergaard J, Mogelvang R, Moller CH, Kandler K, Ravn H, Hassager C, Kober L, Nilsson JC. Efficacy of a glucagon-like peptide-1 agonist and restrictive versus liberal oxygen supply in patients undergoing coronary artery bypass grafting or aortic valve replacement: study protocol for a 2-by-2 factorial designed, randomised clinical trial. BMJ Open. 2021 Nov 5;11(11):e052340. doi: 10.1136/bmjopen-2021-052340.

  PMID: 34740932 DERIVED

MeSH Terms

Conditions

Coronary Disease; Shock, Cardiogenic; Renal Insufficiency; Stroke; Brain Injuries; Aortic Valve Disease

Interventions

Exenatide; Oxygen; Serum Albumin, Human; Albumins

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Shock; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Heart Valve Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors; Chalcogens; Elements; Inorganic Chemicals; Gases; Serum Albumin; Proteins; Blood Proteins

Study Officials

• Peter Skov Olsen, MD, DMSc

  Rigshospitalet, Denmark

  STUDY DIRECTOR

• Jens Christian Nilsson, MD, PhD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

• Lars Køber, MD, DMSc

  Rigshospitalet, Denmark

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Professor

Study Record Dates

• First Submitted: December 6, 2015
• First Posted: February 4, 2016
• Study Start: February 1, 2016
• Primary Completion: September 1, 2024
• Study Completion: September 1, 2024
• Last Updated: August 28, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)