Abstract Body (Do not enter title and authors here): Hypothesis and Purpose:
Restrictive compared to liberal oxygenation during cardio-pulmonary bypass (CPB) and the first hour after weaning from CPB reduces the mortality and morbidity from heart, brain, and kidney injury in patients undergoing cardiac surgery.

Study Design and Methods:
The GLORIOUS trial (NCT02673931) was an investigator-initiated, 2-by-2, single-center, randomized clinical trial. The two interventions were assumed to be independent from each other, and the present abstract reports one intervention. The other intervention (a GLP-1 analog vs. placebo) will be reported separately.

Sample Size:
1400 patients.

Population Studied:
Adult patients undergoing elective or subacute CPB-assisted coronary artery bypass grafting (CABG) and/or surgical aortic valve replacement (AVR).

Intervention:
A conservative oxygenation strategy defined as an FiO₂ of 50% versus a liberal oxygenation strategy defined as an FiO₂ of 100% during CPB and for the first hour after weaning.

Power Calculations:
Interaction between the two interventions were not expected, and the sample size estimation did not account for effect modification. At an alpha-level of 0.05 and a power of 0.8, the trial would be able to show a 25% reduction in the primary endpoint if 1400 patients were included with an event rate of 23% (i.e. 323 events). The trial was event-driven and follow-up has been concluded after 323 events were reached.

Primary End Points:
Time to the first occurring co-primary endpoint 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 a number of predefined safety endpoints during index admission including surgical site infection, hypoglycemia, pancreatitis, a relative reduction of ejection fraction of 50% compared to baseline, reoperation for bleeding and any cause, post-surgery myocardial infarction. Finally, re-admission for cardiovascular causes within 12 months.

Outcome:
From February 2016 through December 2021, a total of 1400 patients were included in the study. Follow-up was concluded in June 2024. The study will be un-blinded by 27^th of August 2024. The main results for the two interventions of the GLORIOUS trial are submitted for AHA’s late breaking session as two separate abstracts. If accepted, we plan to submit the two main articles for simultaneous publication.