We investigate the efficacy of commercially available GLP-1 analog for reducing organ damage in patients undergoing heart surgery (i.e. coronary artery bypass grafting and/or aortic valve replacement). In addition we investigate the efficacy of restrictive versus liberal oxygenation (i.e. FiO2 50% versus FiO2 100%) for reducing organ damage during weaning after heart surgery. The study is a two-by-two factorial designed randomized clinical trial. MedDRA version: 20.0 Level: LLT Classification c
Conditions
Interventions
Trade Name: Byetta
Product Name: Byetta
Product Code: EU/1/06/362/001-2
Pharmaceutical Form: Solution for infusion
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of
Sponsors
Rigshospitalet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Before any study-specific procedure, including assessments for screening, the appropriate written informed consent must be obtained 2) = 18 years of age at the time of signing informed consent 3) IHD requiring CABG (multi-vessel coronary artery disease or coronary anatomy not suitable for percutaneous coronary intervention) and/or Aortic Valve Disease scheduled for AVR, irrespective of other concomitant valve surgery. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 500 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 900
Exclusion criteria
Exclusion criteria: 1) Obstructive hypertrophic cardiomyopathy, active myocarditis, constrictive pericarditis, untreated hypothyroidism or hyperthyroidism or history of or active acute pancreatitis. 2) Acute (i.e. off hours, within hours surgery), Sub-acute surgery (i.e. the following days are eligible). 3) Known allergy towards Exenatide/Byetta or albumin (vehicle). 4) 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. 5) Recipient of any major organ transplant (e.g. lung, liver, heart) 6) 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) 7) 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. 8) Recent (within 3 months) history of alcohol or illicit drug abuse disorder, based on self-report. 9) Pregnant, based on investigator evaluation (e.g., positive human chorionic gonadotropin test) or currently breast feeding. 10) 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To reduce the degree of post-operative organ damage following coronary artery bypass grafting and/or aortic valve replacement, defined as the composite end point of time to death from any cause, renal dysfunction requiring dialysis, stroke or hospital admission/prolongation with worsening/new onset heart failure (HF). The methods GLP-1 versus placebo peri-operatively and restrictive (FiO2 50%) versus liberal (FiO2 100%) oxygenation during weaning will be tested in a 2-by-2 design.;Secondary Objective: Secondary objectives are to determine the efficacy of a GLP-1 agonist compared to placebo on the individual components of the primary endpoint. Similar analyses are planned for the comparison of restrictive vs. liberal administration of oxygen during weaning from circulatory bypass. Minor manifestations of organ damage will be investigated by comparing the effect of a GLP-1 agonist in pre-defined sub-studies with that of placebo on changes in neuropsychological scores, left ventricular ejection fraction, plasma creatinine and calculated creatinine clearance. ;Primary end point(s): 1)Time to death from any cause or 2)Time to any of the following events a)renal failure requiring any type of renal replacement therapy b)stroke defined as persisting (>24 hours) of any neurological sign or symptom of neurological dysfunction as determined by the treating physician based on available i)clinical information and/or ii)CT scan. MRI performed as part of a substudy will not be used for the definition of stroke and/or c)new onset/worsening heart failure defined as i)need for mechanical circulatory support at the ICU, ii)inability to close the sternotomy due post-surgical hemodynamic instability and/or iii)persistent (>48 hours from initiation of first surgical procedure after randomization) need for inotropic hemodynamic support iv)Admission for heart failure during follow-up following discharge from the index admission. ;Timepoint(s) of evaluation of this | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: • Time to death from any cause • Time to death or stroke (as defined above) • Time to death or renal dysfunction requiring dialysis (as defined above) • Time to death or new hospitalization for heart failure during follow-up following discharge from the index admission • Time to death or new onset/worsening in-hospital heart failure (as defined above) • Change from baseline in patient-reported outcome (PRO), focusing on CPC and mRS scales as well as ‘two simple questions’ at 6 months follow up • In-hospital death from any cause or hospital prolongation with renal failure requiring dialysis, stroke or new onset/worsening heart failure. ;Timepoint(s) of evaluation of this end point: A 12-month follow-up for the secondary endpoint is planned. | — |
Countries
Denmark
Contacts
Public ContactHjertemedicinsk Klinik
Rigshospitalet
Outcome results
None listed