Abstract Body (Do not enter title and authors here): Hypothesis and Purpose:
Administering the GLP-1 analog exenatide prior to cardio-pulmonary bypass-assisted (CPB) coronary artery bypass grafting (CABG) and/or aortic valve replacement (AVR) is hypothesized to reduce mortality and morbidity related to heart, brain, and kidney injury.

Study Design and Methods:
The GLORIOUS trial (NCT02673931) was an investigator-initiated, single-center, 2-by-2, randomized clinical trial. The two interventions were considered independent, and this abstract reports on one of those interventions. The other intervention (restrictive vs. liberal oxygenation during cardio-pulmonary bypass) will be reported separately.

Sample Size:
1400 patients.

Population Studied:
Adult patients scheduled for elective or subacute CPB-assisted CABG and/or surgical AVR.

Intervention:
A 6 hour and 15 minutes infusion of either 17.4 μg of exenatide (Byetta®, Lilly) or placebo initiated prior to the induction of anesthesia in a double-blind fashion.

Power Calculations:
No interaction between the two interventions was expected, and the sample size estimation did not account for effect modification. With an alpha-level of 0.05 and a power of 0.8, the trial aimed to demonstrate a 25% reduction in the primary endpoint, assuming an event rate of 23% (i.e., 323 events) in 1400 patients. The trial was event-driven and follow-up has been concluded after 323 total events were reached.

Primary End Points:
Time to the first occurrence of any of the co-primary endpoints during follow-up, including death, renal failure requiring renal replacement therapy, stroke, new-onset heart failure, or any re-admission for heart failure.

Secondary End Points:
Incidence of predefined safety endpoints during the index admission, such as surgical site infection, hypoglycemia, pancreatitis, a relative reduction of ejection fraction by 50% compared to baseline, reoperation for bleeding and any cause, and post-surgery myocardial infarction. Additionally, re-admission for cardiovascular causes within 12 months was monitored.

Outcome:
From February 2016 to December 2021, 1400 patients were enrolled in the study, with follow-up concluding in June 2024. The study will be un-blinded on August 27, 2024. The main results for the two interventions of the GLORIOUS trial have been submitted as separate abstracts for AHA’s late-breaking session. If accepted, the two primary articles will be submitted for simultaneous publication.