دورية أكاديمية
Dapagliflozin for Critically Ill Patients With Acute Organ Dysfunction: The DEFENDER Randomized Clinical Trial.
| العنوان: | Dapagliflozin for Critically Ill Patients With Acute Organ Dysfunction: The DEFENDER Randomized Clinical Trial. |
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| المؤلفون: | Tavares CAM; Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil.; Geriatric Cardiology Unit, Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil., Azevedo LCP; Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil., Rea-Neto Á; Center for Studies and Research in Intensive Care Medicine, Curitiba, Brazil.; Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil.; Hospital Santa Casa Curitiba, Curitiba, Brazil., Campos NS; Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil.; Hospital M´Boi Mirim, São Paulo, Brazil., Amendola CP; Hospital de Câncer de Barretos, Barretos, Brazil., Kozesinski-Nakatani AC; Center for Studies and Research in Intensive Care Medicine, Curitiba, Brazil.; Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil.; Hospital Santa Casa Curitiba, Curitiba, Brazil., David-João PG; Hospital M´Boi Mirim, São Paulo, Brazil., Lobo SM; Intensive Care Division, Hospital de Base, Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, Brazil., Filiponi TC; Hospital Universitário São Francisco de Assis na Providência de Deus, Bragança Paulista, Brazil., Almeida GMB; Hospital de Emergência Dr Daniel Houly, Arapiraca, Brazil., Bergo RR; Hospital Santa Lucia, Poços de Caldas, Brazil., Guimarães-Júnior MRR; Santa Casa de Misericórdia de Barretos, Barretos, Brazil., Figueiredo RC; Hospital Maternidade São José, Colatina, Brazil., Castro JR; Hospital Municipal de Aparecida de Goiânia, Aparecida de Goiânia, Brazil., Schuler CJ; Hospital Nossa Senhora de Oliveira, Vacaria, Brazil., Westphal GA; Centro Hospitalar Unimed, Joinville, Brazil., Carioca ACR; Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil., Monfradini F; Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil., Nieri J; Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil., Neves FMO; Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil., Paulo JA; Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil., Albuquerque CSN; Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil., Silva MCR; Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil., Kosiborod MN; Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City., Pereira AJ; Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil., Damiani LP; Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil., Corrêa TD; Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil., Serpa-Neto A; Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil.; Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.; Department of Intensive Care, Austin Hospital, Melbourne, Australia., Berwanger O; Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil.; George Institute for Global Health, London, United Kingdom.; Imperial College London, London, United Kingdom., Zampieri FG; Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil.; Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta and Alberta Health Services, Edmonton, Canada. |
| مؤلفون مشاركون: | DEFENDER Investigators |
| المصدر: | JAMA [JAMA] 2024 Aug 06; Vol. 332 (5), pp. 401-411. |
| نوع المنشور: | Journal Article; Randomized Controlled Trial; Multicenter Study; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Medical Association Country of Publication: United States NLM ID: 7501160 Publication Model: Print Cited Medium: Internet ISSN: 1538-3598 (Electronic) Linking ISSN: 00987484 NLM ISO Abbreviation: JAMA Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Chicago : American Medical Association, 1960- |
| مواضيع طبية MeSH: | Benzhydryl Compounds*/therapeutic use , Glucosides*/therapeutic use , Glucosides*/adverse effects , Critical Illness* , Sodium-Glucose Transporter 2 Inhibitors*/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors*/adverse effects , Intensive Care Units* , Length of Stay* , Hospital Mortality*, Humans ; Female ; Male ; Middle Aged ; Aged ; Renal Replacement Therapy ; Multiple Organ Failure/drug therapy |
| مستخلص: | 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. |
| التعليقات: | Comment in: JAMA. 2024 Aug 6;332(5):377-379. doi: 10.1001/jama.2024.10171. (PMID: 38873705) |
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| فهرسة مساهمة: | Investigator: J Souza; L Sanches; M Castro; M Cunha; F Fagundes; J Siqueira; G Westphal; C Ospina; E Silva; J Ramos; M Machado; R Fermamdes; C Lunardi; L Radun; A Moura; E Silva; L Dantas; L Gomes; ML Silva; Y Nunes; AB Lino; G Barros; JP Nunes; M Barbosa; G Souza; H Duarte; H Mota; J Castro; M Olambrada; R Borges; L Barros; N Pereira; M Tavares; G Joia; G Cordeiro; N Mattos; V Lanza; V Silva; MA Dracoulakis; N Alvaia; C Vieira; I Freitas; B Conceição; J Borges; A Silva; T Caroline; J Jesus; A Santos; B Vieira; I Guerreiro; L Oliveira; L Esteves; R Bolini; E Carvalho; A Lacerda; A Ferreira; G Sica; L Oliveira; MDV Guedes; O Gebara; AP Espirito Santo; AT Lopes; H Ribeiro; P Tomba; V Morete; J Almeida; C Silva; L Gato; L Inada; C Dias; F Dall'Orto; G Melo; AR Silva; G Ribeiro; K Ferreira; R Biondi; S Ramalho; D Silva; E Garbin; I Pereira; L Nunes; R Lacourt; C Loss; J Silva; C Jorge; G Denerdin; K Millani; L Machado; AC Affonso; J Garcia; T Oiafuso; L Camargo; K Morais; A Angeli; C Pradela; G Marques; J Silva; MF Santos; M Zini; K Candido; T Silva; V Barros; M Pool; F Serra; A Coelho; L Vieira; T Galvao; A Tognon; M Dozza; S Henrich; A Giordani; A Menegasso; M Antunes; N Gosmano; S Moura; T Costa; V Canato; G Queiroz; M Gonçalvez; M Zanona; H Dias; EBJ Ferraz; C Rossi; L Pozzo; D Moia; RVP Soares; RM Marino; BL Moreno; A Serapião; R Momesso; BGD Silva; CS Santos; EJ Santos; BDS Sampaio; LPA Piano |
| سلسلة جزيئية: | ClinicalTrials.gov NCT05558098 |
| المشرفين على المادة: | 1ULL0QJ8UC (dapagliflozin) 0 (Benzhydryl Compounds) 0 (Glucosides) 0 (Sodium-Glucose Transporter 2 Inhibitors) |
| تواريخ الأحداث: | Date Created: 20240614 Date Completed: 20240806 Latest Revision: 20240809 |
| رمز التحديث: | 20240809 |
| مُعرف محوري في PubMed: | PMC11304119 |
| DOI: | 10.1001/jama.2024.10510 |
| PMID: | 38873723 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1538-3598 |
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| DOI: | 10.1001/jama.2024.10510 |