Dapagliflozin in Respiratory Failure in Patients With COVID-19
Condition: COVID-19
MeSH terms: COVID-19; Respiratory Insufficiency
Intervention: Dapagliflozin 10 milligram (mg); Placebo
Intervention description: Active Comparator: Dapagliflozin 10 mg; Placebo Comparator
Intervention MeSH terms: Dapagliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1250.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: sodium-glucose cotransporter-2 inhibitor (SGLT2i); dapagliflozin; COVID-19

Summary:

      This is an international, multicenter, parallel-group, randomized, double-blind, placebo
      controlled, study in hospitalized adult patients with coronavirus disease 2019 (COVID-19) in
      the United States, Brazil, Mexico, Argentina, India, Canada, and United Kingdom. The study is
      evaluating the effect of dapagliflozin 10 milligrams versus placebo, given once daily for 30
      days in addition to background local standard of care therapy, on reducing complications and
      all-cause mortality, or improving clinical recovery.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provision of informed consent

          2. Male or female patients aged ≥18 years

          3. Currently hospitalized

          4. Hospital admission no more than 4 days prior to screening

          5. Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by
             laboratory testing within 10 days prior to screening, or strongly suspected SARS-CoV-2
             infection on presentation

          6. Chest radiography or computerized tomography (CT) findings that, in the opinion of the
             investigator, are consistent with coronavirus disease 2019 (COVID-19)

          7. Blood oxygen saturation (SpO2) ≥ 94% while receiving low-flow supplemental oxygen (5
             liters or less)

          8. Medical history of at least one of the following:

               1. hypertension

               2. type 2 diabetes

               3. atherosclerotic cardiovascular disease

               4. heart failure (with either reduced or preserved left ventricular ejection
                  fraction (LVEF))

               5. chronic kidney disease stage 3 to 4 (estimated glomerular filtration rate (eGFR)
                  between 25 to 60 mL/min/1.73 m2)

        Key Exclusion Criteria:

          1. Respiratory decompensation requiring mechanical ventilation (includes invasive or non
             invasive ventilation, continuous positive airway pressure (CPAP), or bilevel positive
             airway pressure (BiPAP))

          2. Expected need for mechanical ventilation (includes invasive or non-invasive
             ventilation, CPAP, or BiPAP) within the next 24 hours

          3. Expected survival of less than 24 hours at the time of presentation, in the judgement
             of the investigator

          4. eGFR <25 mL/min/1.73 m2 or receiving renal replacement therapy/dialysis

          5. Systolic blood pressure <95 mmHg and/or requirement for vasopressor treatment and/or
             inotropic or mechanical circulatory support at Screening

          6. History of type 1 diabetes mellitus

          7. History of diabetic ketoacidosis

          8. Currently receiving or has received in the last 14 days, experimental immune
             modulators and/or monoclonal antibody therapies for COVID-19

          9. Current treatment with any sodium-glucose cotransporter-2 inhibitor (SGLT2i) (eg,
             dapagliflozin, canagliflozin, empagliflozin, ertugliflozin) or having received
             treatment with any SGLT2i within 4 weeks prior to screening

         10. Current participation in another interventional clinical trial (with an
             investigational drug) that is not an observational registry

               -  Note that use of rescue therapies including immune modulators, monoclonal
                  antibody therapies, antiviral therapies, and other agents that are approved or
                  being used through open-label compassionate/expanded use programs or in
                  accordance with the local standard of care is permitted during the study.