ACTIV-4a (SGLT2 inhibitors)
Trial question
What is the effect of SGLT-2 inhibitors on survival free of organ support in hospitalized patients with COVID-19 infection?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
42.0% female
58.0% male
N = 575
575 patients (242 female, 333 male).
Inclusion criteria: hospitalized patients with COVID-19 infection.
Key exclusion criteria: imminent death; requirement of chronic mechanical ventilation via tracheostomy before hospitalization; pregnancy; T1DM; history of diabetic ketoacidosis; eGFR < 20 mL/min/1.73 m² and/or requirement for RRT.
Interventions
N=287 SGLT2 inhibitors (dapagliflozin 10 mg, empagliflozin 10 mg, canagliflozin 100 mg, or ertugliflozin 5 mg PO once daily for 30 days plus standard care).
N=288 standard care alone (standard of care for 30 days, including either therapeutic or prophylactic dose heparin).
Primary outcome
Organ support-free days
21 days
21 days
21.0 days
15.8 days
10.5 days
5.3 days
0.0 days
SGLT2
inhibitors
Standard care
alone
No significant
difference ↔
No significant difference in organ support-free days (21 days vs. 21 days; OR 0.74, 95% CI 0.48 to 1.13).
Secondary outcomes
No significant difference in death in the hospital (9% vs. 8%; OR 1.1, 95% CI 0.58 to 1.95).
No significant difference in death at day 90 (13% vs. 14.6%; HR 0.91, 95% CI 0.58 to 1.43).
No significant difference in major thrombotic event or in-hospital death at day 28 (7% vs. 8%; ARD -0.3, 95% CI -4.6 to 4).
Safety outcomes
No significant differences in thrombotic events, major bleeding, AKI.
Conclusion
In hospitalized patients with COVID-19 infection, SGLT2 inhibitors were not superior to standard care alone with respect to organ support-free days.
Reference
Mikhail N Kosiborod, Sheryl L Windsor, Orly Vardeny et al. Effect of sodium-glucose co-transporter-2 inhibitors on survival free of organ support in patients hospitalised for COVID-19 (ACTIV-4a): a pragmatic, multicentre, open-label, randomised, controlled, platform trial. Lancet Diabetes Endocrinol. 2024 Oct;12(10):725-734.
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