TY - JOUR
T1 - Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19)
T2 - a randomised, double-blind, placebo-controlled, phase 3 trial
AU - Kosiborod, Mikhail N.
AU - Esterline, Russell
AU - Furtado, Remo H.M.
AU - Oscarsson, Jan
AU - Gasparyan, Samvel B.
AU - Koch, Gary G.
AU - Martinez, Felipe
AU - Mukhtar, Omar
AU - Verma, Subodh
AU - Chopra, Vijay
AU - Buenconsejo, Joan
AU - Langkilde, Anna Maria
AU - Ambery, Philip
AU - Tang, Fengming
AU - Gosch, Kensey
AU - Windsor, Sheryl L.
AU - Akin, Emily E.
AU - Soares, Ronaldo V.P.
AU - Moia, Diogo D.F.
AU - Aboudara, Matthew
AU - Hoffmann Filho, Conrado Roberto
AU - Feitosa, Audes D.M.
AU - Fonseca, Alberto
AU - Garla, Vishnu
AU - Gordon, Robert A.
AU - Javaheri, Ali
AU - Jaeger, Cristiano P.
AU - Leaes, Paulo E.
AU - Nassif, Michael
AU - Pursley, Michael
AU - Silveira, Fabio Serra
AU - Barroso, Weimar Kunz Sebba
AU - Lazcano Soto, José Roberto
AU - Nigro Maia, Lilia
AU - Berwanger, Otavio
N1 - Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/9
Y1 - 2021/9
N2 - Background: COVID-19 can lead to multiorgan failure. Dapagliflozin, a SGLT2 inhibitor, has significant protective benefits for the heart and kidney. We aimed to see whether this agent might provide organ protection in patients with COVID-19 by affecting processes dysregulated during acute illness. Methods: DARE-19 was a randomised, double-blind, placebo-controlled trial of patients hospitalised with COVID-19 and with at least one cardiometabolic risk factor (ie, hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease). Patients critically ill at screening were excluded. Patients were randomly assigned 1:1 to dapagliflozin (10 mg daily orally) or matched placebo for 30 days. Dual primary outcomes were assessed in the intention-to-treat population: the outcome of prevention (time to new or worsened organ dysfunction or death), and the hierarchial composite outcome of recovery (change in clinical status by day 30). Safety outcomes, in patients who received at least one study medication dose, included serious adverse events, adverse events leading to discontinuation, and adverse events of interest. This study is registered with ClinicalTrials.gov, NCT04350593. Findings: Between April 22, 2020 and Jan 1, 2021, 1250 patients were randomly assigned with 625 in each group. The primary composite outcome of prevention showed organ dysfunction or death occurred in 70 patients (11·2%) in the dapagliflozin group, and 86 (13·8%) in the placebo group (hazard ratio [HR] 0·80, 95% CI 0·58–1·10; p=0·17). For the primary outcome of recovery, 547 patients (87·5%) in the dapagliflozin group and 532 (85·1%) in the placebo group showed clinical status improvement, although this was not statistically significant (win ratio 1·09, 95% CI 0·97–1·22; p=0·14). There were 41 deaths (6·6%) in the dapagliflozin group, and 54 (8·6%) in the placebo group (HR 0·77, 95% CI 0·52–1·16). Serious adverse events were reported in 65 (10·6%) of 613 patients treated with dapagliflozin and in 82 (13·3%) of 616 patients given the placebo. Interpretation: In patients with cardiometabolic risk factors who were hospitalised with COVID-19, treatment with dapagliflozin did not result in a statistically significant risk reduction in organ dysfunction or death, or improvement in clinical recovery, but was well tolerated. Funding: AstraZeneca.
AB - Background: COVID-19 can lead to multiorgan failure. Dapagliflozin, a SGLT2 inhibitor, has significant protective benefits for the heart and kidney. We aimed to see whether this agent might provide organ protection in patients with COVID-19 by affecting processes dysregulated during acute illness. Methods: DARE-19 was a randomised, double-blind, placebo-controlled trial of patients hospitalised with COVID-19 and with at least one cardiometabolic risk factor (ie, hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease). Patients critically ill at screening were excluded. Patients were randomly assigned 1:1 to dapagliflozin (10 mg daily orally) or matched placebo for 30 days. Dual primary outcomes were assessed in the intention-to-treat population: the outcome of prevention (time to new or worsened organ dysfunction or death), and the hierarchial composite outcome of recovery (change in clinical status by day 30). Safety outcomes, in patients who received at least one study medication dose, included serious adverse events, adverse events leading to discontinuation, and adverse events of interest. This study is registered with ClinicalTrials.gov, NCT04350593. Findings: Between April 22, 2020 and Jan 1, 2021, 1250 patients were randomly assigned with 625 in each group. The primary composite outcome of prevention showed organ dysfunction or death occurred in 70 patients (11·2%) in the dapagliflozin group, and 86 (13·8%) in the placebo group (hazard ratio [HR] 0·80, 95% CI 0·58–1·10; p=0·17). For the primary outcome of recovery, 547 patients (87·5%) in the dapagliflozin group and 532 (85·1%) in the placebo group showed clinical status improvement, although this was not statistically significant (win ratio 1·09, 95% CI 0·97–1·22; p=0·14). There were 41 deaths (6·6%) in the dapagliflozin group, and 54 (8·6%) in the placebo group (HR 0·77, 95% CI 0·52–1·16). Serious adverse events were reported in 65 (10·6%) of 613 patients treated with dapagliflozin and in 82 (13·3%) of 616 patients given the placebo. Interpretation: In patients with cardiometabolic risk factors who were hospitalised with COVID-19, treatment with dapagliflozin did not result in a statistically significant risk reduction in organ dysfunction or death, or improvement in clinical recovery, but was well tolerated. Funding: AstraZeneca.
UR - http://www.scopus.com/inward/record.url?scp=85112858584&partnerID=8YFLogxK
U2 - 10.1016/S2213-8587(21)00180-7
DO - 10.1016/S2213-8587(21)00180-7
M3 - Article
C2 - 34302745
AN - SCOPUS:85112858584
SN - 2213-8587
VL - 9
SP - 586
EP - 594
JO - The Lancet Diabetes and Endocrinology
JF - The Lancet Diabetes and Endocrinology
IS - 9
ER -