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. 2023 Dec 22;35(3):256-265.
doi: 10.5935/2965-2774.20230129-en. eCollection 2023.

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

[Article in English, Portuguese]
Caio de Assis Moura Tavares  1 , Luciano César Pontes de Azevedo  1 , Álvaro Rea-Neto  2 , Niklas Söderberg Campos  3 , Cristina Prata Amendola  4 , Ricardo Reinaldo Bergo  5 , Amanda Christina Kozesinski-Nakatani  2 , Paula Geraldes David-João  3 , Glauco Adrieno Westphal  6 , Mário Roberto Rezende Guimarães Júnior  7 , Suzana Margareth Ajeje Lobo  8 , Marcos Soares Tavares  9 , Marianna Deway Andrade Dracoulakis  10 , Guilherme Martins de Souza  11 , Guacyra Margarita Batista de Almeida  12 , Otavio Celso Eluf Gebara  13 , Pablo Oscar Tomba  14 , Camila Santos N Albuquerque  1 , Mariana Castaldi Ramalho Silva  1 , Adriano José Pereira  1 , Lucas Petri Damiani  1 , Thiago Domingos Corrêa  1 , Ary Serpa-Neto  1 , Otavio Berwanger  1 , Fernando Godinho Zampieri  1
Affiliations

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

[Article in English, Portuguese]
Caio de Assis Moura Tavares et al. Crit Care Sci. .

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.

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Conflict of interest statement

Conflicts of interest: None.

Figures

Figure 1
Figure 1
DEFENDER study design and flow chart.
Figure 2
Figure 2
Flowchart for the win ratio according to the hierarchy of the primary outcome.
Figure 3
Figure 3
Lower boundary of the win ratios 95% confidence intervals obtained through 10,000 simulations on samples of 500 patients.
See this image and copyright information in PMC

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