Dapagliflozin in Respiratory Failure in Patients With COVID-19 - DARE-19

Contribution To Literature:

The DARE-19 trial showed that dapagliflozin did not significantly reduce organ dysfunction or death, or improve recovery, compared with placebo among noncritically ill hospitalized patients with COVID-19.

Description:

The goal of the trial was to assess the safety and efficacy of dapagliflozin among eligible hospitalized patients with coronavirus disease 2019 (COVID-19).  

Study Design

Eligible patients were randomized in a 1:1 fashion to either dapagliflozin 10 mg daily (n = 625) or placebo (n = 625). 

  • Total number of patients: 1,250
  • Duration of follow-up: 90 days
  • Mean patient age: 62 years
  • Percentage female: 43%

Inclusion criteria:

  • Hospitalization with confirmed/suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for ≤4 days
  • O2 saturation of ≥94% on ≤5 L/min
  • Chest X-ray findings c/w COVID-19
  • ≥1 risk factor (hypertension, type 2 diabetes, atherosclerotic cardiovascular disease [ASCVD], heart failure, chronic kidney disease)

Exclusion criteria:

  • Type 1 diabetes mellitus
  • Critical illness on presentation
  • Estimated glomerular filtration rate: <25 ml/min/1.73 m2
  • Prior diabetic ketoacidosis

Other salient features:

  • Mean systolic blood pressure: 127 mm Hg
  • Type 2 diabetes mellitus: 51%
  • ASCVD: 16%

Principal Findings:

The primary endpoint, organ failure or death, for dapagliflozin vs. placebo, was: 11.2% vs. 13.8% (p = 0.17).

  • Primary outcome of recovery: Win ratio, 1.09 (95% confidence interval [CI] 0.97-1.22, p = 0.14)

Secondary outcomes for dapagliflozin vs. placebo:

  • Composite kidney endpoint: 7.7% vs. 10.4% (hazard ratio 0.74, 95% CI 0.50-1.07)
  • All-cause mortality: 6.6% vs. 8.6% (p > 0.05)

Interpretation:

The results of this trial indicate that dapagliflozin did not significantly reduce organ dysfunction or death, or improve recovery compared with placebo among noncritically ill hospitalized patients with COVID-19. Patients with and without type 2 diabetes were included. Very few patients had baseline heart failure or chronic kidney disease. Numerically, events with lower with dapagliflozin, especially for the composite kidney endpoint. Side effects were similar. It is possible that a larger trial would have shown a benefit with dapagliflozin, although this needs to be proven. The exact mechanism (of a possible benefit) is also unclear.

References:

Presented by Dr. Mikhail Kosiborod at the American College of Cardiology Virtual Annual Scientific Session (ACC 2021), May 16, 2021.

Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Hypertension

Keywords: ACC21, ACC Annual Scientific Session, Blood Pressure, Coronavirus, COVID-19, Diabetes Mellitus, Type 2, Heart Failure, Hypertension, Kidney Diseases, Metabolic Syndrome, Multiple Organ Failure, Primary Prevention, Renal Insufficiency, Chronic, Respiratory Insufficiency, Risk Factors, SARS-CoV-2, X-Rays


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