Dapagliflozin for Critically Ill Patients With Acute Organ Dysfunction
Caio A.M. Tavares, Luciano César Pontes Azevedo, Álvaro Réa-Neto, Niklas Söderberg Campos, Cristina Prata Amêndola, Amanda Christina Kozesinski-Nakatani, Paula Geraldes David-João, Suzana Margareth Lobo, Thiago Corsi Filiponi, Guacyra Margarita Batista de Almeida, Ricardo Reinaldo Bergo, Mário R. R. Guimarães-Júnior, Rodrigo C. Figueiredo, Joan R. Castro, Clewer J. Schuler, Glauco Adrieno Westphal, Ana Carla Carioca, Frederico Monfradini, Josué Nieri, Flavia M. O. Neves, Jaqueline A. Paulo, Camila Santos N Albuquerque, Mariana Castaldi Ramalho Silva, Mikhail Kosiborod, Adriano José Pereira, Lucas Petri Damiani, Thiago Domingos Corrêa, Ary Serpa Neto, Otávio Berwanger, Fernando G. Zampieri, DEFENDER Investigators, Juliano Luiz de Souza, Luciana Sanches, M. C. Castro, Mariana Sequetin Cunha, Flávia Maiara Lima Fagundes, Juan Siqueira, Glauco Adrieno Westphal, C.F. Girlado Ospina, Evelin Silva, Juliano Ramos, Miriam Machado, Ruthy Fermamdes, Camila Lunardi, Luana Caroline Radun, Andervan Moura, Evânio da Silva, Lívia de Azevedo Dantas, Livia Gomes, Maria Luzia Silva, Yolanda Nunes, Ana Beatriz Lino, Gabrielly Barros, João Pedro Nunes, M. P. T. Barbosa, Guilherme Rocha Lino de Souza, Hugo Miguel Santos Duarte, H C da Mota, Joan Castro, Mayler Olambrada, Rafael Borges, Luciana Barros, Nélson Pereira, Marcos Tavares, Gabriela Joia, Gabriella Cordeiro, Natalia Mattos, Vinicius Lanza, Victória N. G. Silva, Marianna A Dracoulakis, Natalia Alvaia, Camilla de Oliveira Vieira, Izabela Freitas, Beatriz Santos Pereira Conceicao, Jaqueline A.R. Borges, Aline Silva, Thais Caroline, Josiane Jesus, Allan O. Santos, Bruno Müller Vieira, Isabelle Guerreiro, Luciana Butini Oliveira, Luiz Alberto Esteves, Rodrigo Bolini, Edmilson Carvalho, Adilson Lacerda, Aline Miranda Ferreira, Gustavo Sica, Lara Leite de Oliveira, Maria das Vitórias Guedes, Otávio Gebara, Ana Paula Espirito Santo, Ana Tarina Alvarez Lopes, Hevelton Ribeiro, Pablo Oscar Tomba, Vislaine Do Aguiar Morete, Joyce S. F. D. de Almeida, Cláudia Silva, Luana Gato, Leticia Inada
Abstract
Importance: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors improve outcomes in patients with type 2 diabetes, heart failure, and chronic kidney disease, but their effect on outcomes of critically ill patients with organ failure is unknown. Objective: To determine whether the addition of dapagliflozin, an SGLT-2 inhibitor, to standard intensive care unit (ICU) care improves outcomes in a critically ill population with acute organ dysfunction. Design, Setting, and Participants: Multicenter, randomized, open-label, clinical trial conducted at 22 ICUs in Brazil. Participants with unplanned ICU admission and presenting with at least 1 organ dysfunction (respiratory, cardiovascular, or kidney) were enrolled between November 22, 2022, and August 30, 2023, with follow-up through September 27, 2023. Intervention: Participants were randomized to 10 mg of dapagliflozin (intervention, n = 248) plus standard care or to standard care alone (control, n = 259) for up to 14 days or until ICU discharge, whichever occurred first. Main Outcomes and Measures: The primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay through 28 days, analyzed using the win ratio method. Secondary outcomes included the individual components of the hierarchical outcome, duration of organ support-free days, ICU, and hospital stay, assessed using bayesian regression models. Results: Among 507 randomized participants (mean age, 63.9 [SD, 15] years; 46.9%, women), 39.6% had an ICU admission due to suspected infection. The median time from ICU admission to randomization was 1 day (IQR, 0-1). The win ratio for dapagliflozin for the primary outcome was 1.01 (95% CI, 0.90 to 1.13; P = .89). Among all secondary outcomes, the highest probability of benefit found was 0.90 for dapagliflozin regarding use of kidney replacement therapy among 27 patients (10.9%) in the dapagliflozin group vs 39 (15.1%) in the control group. Conclusion and Relevance: The addition of dapagliflozin to standard care for critically ill patients and acute organ dysfunction did not improve clinical outcomes; however, confidence intervals were wide and could not exclude relevant benefits or harms for dapagliflozin. Trial Registration: ClinicalTrials.gov Identifier: NCT05558098.