Dapagliflozin for Critically Ill Patients With Acute Organ Dysfunction
Author:
Tavares Caio A. M.12, Azevedo Luciano C. P.1, Rea-Neto Álvaro345, Campos Niklas S.16, Amendola Cristina P.7, Kozesinski-Nakatani Amanda C.345, David-João Paula G.6, Lobo Suzana M.8, Filiponi Thiago C.9, Almeida Guacyra M. B.10, Bergo Ricardo R.11, Guimarães-Júnior Mário R. R.12, Figueiredo Rodrigo C.13, Castro Joan R.14, Schuler Clewer J.15, Westphal Glauco A.16, Carioca Ana C. R.1, Monfradini Frederico1, Nieri Josue1, Neves Flavia M. O.1, Paulo Jaqueline A.1, Albuquerque Camila S. N.1, Silva Mariana C. R.1, Kosiborod Mikhail N.17, Pereira Adriano J.1, Damiani Lucas P.1, Corrêa Thiago D.1, Serpa-Neto Ary11819, Berwanger Otavio12021, Zampieri Fernando G.122, , Souza Juliano23, Sanches Luciana23, Castro Maisa23, Cunha Mariana23, Fagundes Flávia23, Siqueira Juan23, Westphal Glauco23, Ospina Cristian23, Silva Evelin23, Ramos Juliano23, Machado Miriam23, Fermamdes Ruthy23, Lunardi Camila23, Radun Luana23, Moura Andervan23, Silva Evanio23, Dantas Livia23, Gomes Livia23, Silva Maria Luzia23, Nunes Yolanda23, Lino Ana Beatriz23, Barros Gabrielly23, Nunes João Pedro23, Barbosa Marivalda23, Souza Guilherme23, Duarte Hugo23, Mota Hannah23, Castro Joan23, Olambrada Mayler23, Borges Rafael23, Barros Luciana23, Pereira Nelson23, Tavares Marcos23, Joia Gabriela23, Cordeiro Gabriella23, Mattos Natalia23, Lanza Vinicius23, Silva Victoria23, Dracoulakis Marianna A23, Alvaia Natalia23, Vieira Camilla23, Freitas Izabela23, Conceição Beatriz23, Borges Jaqueline23, Silva Aline23, Caroline Thais23, Jesus Josiane23, Santos Allan23, Vieira Bruno23, Guerreiro Isabelle23, Oliveira Luciana23, Esteves Luiz23, Bolini Rodrigo23, Carvalho Edmilson23, Lacerda Adilson23, Ferreira Aline23, Sica Gustavo23, Oliveira Lara23, Guedes Maria das Vitórias23, Gebara Otavio23, Espirito Santo Ana Paula23, Lopes Ana Tarina23, Ribeiro Hevelton23, Tomba Pablo23, Morete Vislaine23, Almeida Joyce23, Silva Claudia23, Gato Luana23, Inada Leticia23, Dias Claire23, Dall’Orto Frederico23, Melo Graziela23, Silva Ana Roberta23, Ribeiro Gislayne23, Ferreira Kemilys23, Biondi Rodrigo23, Ramalho Sergio23, Silva Derick23, Garbin Eduardo23, Pereira Ingrid23, Nunes Luana23, Lacourt Rayane23, Loss Cintia23, Silva Jackelyne23, Jorge Claudio23, Denerdin Graziela23, Millani Karla23, Machado Luana23, Affonso Ana Carolina23, Garcia Juliane23, Oiafuso Tatiane23, Camargo Luana23, Morais Kaio23, Angeli Aline23, Pradela Cassia23, Marques Gustava23, Silva Joelma23, Santos Maria Fernanda23, Zini Marina23, Candido Keulle23, Silva Tamires23, Barros Verônica23, Pool Mariana23, Serra Fabio23, Coelho Alef23, Vieira Lea23, Galvao Tamyres23, Tognon Alexandre23, Dozza Marcos23, Henrich Sabrina23, Giordani Andressa23, Menegasso Aloma23, Antunes Murillo23, Gosmano Nicoli23, Moura Stefany23, Costa Tiberio23, Canato Vitoria23, Queiroz Gabriela23, Gonçalvez Mariana23, Zanona Mariana23, Dias Hellen23, Ferraz Eduardo Bazanelli Junqueira23, Rossi Caroline23, Pozzo Leandro23, Moia Diogo23, Soares Ronaldo Vicente Pereira23, Marino Ramy Machado23, Moreno Bruna Ladeira23, Serapião Arthur23, Momesso Roberta23, Silva Bárbara Gomes da23, Santos Cintia Selles23, Santos Elaine de Jesus23, Sampaio Bruna dos Santos23, Piano Luciana Pereira Almeida de23
Affiliation:
1. Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil 2. Geriatric Cardiology Unit, Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil 3. Center for Studies and Research in Intensive Care Medicine, Curitiba, Brazil 4. Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil 5. Hospital Santa Casa Curitiba, Curitiba, Brazil 6. Hospital M´Boi Mirim, São Paulo, Brazil 7. Hospital de Câncer de Barretos, Barretos, Brazil 8. Intensive Care Division, Hospital de Base, Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, Brazil 9. Hospital Universitário São Francisco de Assis na Providência de Deus, Bragança Paulista, Brazil 10. Hospital de Emergência Dr Daniel Houly, Arapiraca, Brazil 11. Hospital Santa Lucia, Poços de Caldas, Brazil 12. Santa Casa de Misericórdia de Barretos, Barretos, Brazil 13. Hospital Maternidade São José, Colatina, Brazil 14. Hospital Municipal de Aparecida de Goiânia, Aparecida de Goiânia, Brazil 15. Hospital Nossa Senhora de Oliveira, Vacaria, Brazil 16. Centro Hospitalar Unimed, Joinville, Brazil 17. Department of Cardiovascular Disease, Saint Luke’s Mid America Heart Institute, University of Missouri–Kansas City School of Medicine, Kansas City 18. Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia 19. Department of Intensive Care, Austin Hospital, Melbourne, Australia 20. George Institute for Global Health, London, United Kingdom 21. Imperial College London, London, United Kingdom 22. Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta and Alberta Health Services, Edmonton, Canada 23. for the DEFENDER Investigators
Abstract
ImportanceSodium-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.ObjectiveTo 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 ParticipantsMulticenter, 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.InterventionParticipants 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 MeasuresThe 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.ResultsAmong 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 RelevanceThe 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 RegistrationClinicalTrials.gov Identifier: NCT05558098
Publisher
American Medical Association (AMA)
Reference30 articles.
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