Dapagliflozin in patients with critical illness: rationale and design of the DEFENDER study

Abstract

Background Critical illness is a major ongoing health care burden worldwide and is associated with high mortality rates. Sodium-glucose cotransporter-2 inhibitors have consistently shown benefits in cardiovascular and renal outcomes. The effects of sodium-glucose cotransporter-2 inhibitors in acute illness have not been properly investigated. Methods DEFENDER is an investigator-initiated, multicenter, randomized, open-label trial designed to evaluate the efficacy and safety of dapagliflozin in 500 adult participants with acute organ dysfunction who are hospitalized in the intensive care unit. Eligible participants will be randomized 1:1 to receive dapagliflozin 10mg plus standard of care for up to 14 days or standard of care alone. The primary outcome is a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and intensive care unit length of stay, up to 28 days. Safety will be strictly monitored throughout the study. Conclusion DEFENDER is the first study designed to investigate the use of a sodium-glucose cotransporter-2 inhibitor in general intensive care unit patients with acute organ dysfunction. It will provide relevant information on the use of drugs of this promising class in critically ill patients. ClinicalTrials.gov registry NCT05558098

Dapagliflozin for Critically Ill Patients With Acute Organ Dysfunction

“…The trial design and statistical analysis plan (Supplement 2) were previously published. 14 This was an investigatorinitiated, multicenter, open-label, randomized clinical trial conducted across 22 ICUs in Brazil. The trial operations were coordinated by the Academic Research Organization of the Hospital Israelita Albert Einstein.…”