Trial NCT04350593
Publication Kosiborod M, Lancet Diabetes Endo, 2021 (published paper)
Dates: 2020-04-22 to 2021-01-01
Funding: Private (AstraZeneca)
Conflict of interest: Yes
| Methods | |
| RCT Blinding: double blinding | |
| Location :
Multicenter / Argentina, Brazil, Canada, India, Mexico, UK, USA Follow-up duration (days): 30 | |
| Inclusion criteria | At least 18 years of age; hospitalised with laboratory confirmed or clinically suspected SARS-CoV-2 infection no more than 4 days before screening; had oxygen saturation of 94% or greater on supplemental oxygen (no more than 5 L/min); chest radiography findings consistent with COVID-19 pneumonia; and at least one cardiometabolic risk factor: hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease (estimated glomerular filtration rate [eGFR] between 25 mL/min per 1·73 m² and 60 mL/min per 1·73 m²) |
| Exclusion criteria | evidence of critical illness (eg, need for mechanical ventilation, evidence of acute kidney failure, or need for vasopressor support at the time of screening); eGFR of less than 25 mL/min per 1·73 m²; type 1 diabetes; and history of diabetic ketoacidosis. |
| Interventions | |
| Treatment
Dapagliflozin 10 mg orally once daily for 30 days |
|
| Control
Placebo | |
| Participants | |
| Randomized 1250 participants (n1=625 / n2= 625) | |
| Characteristics of participants N=1250 Mean age : 61.4 717 males Severity : Mild: n=0 / Moderate: n=*/ Severe: n=* Critical: n=0 | |
| Primary outcome | |
| In the register 1) Prevention of COVID-19 Complications or death: During the 30-day treatment period, time to first occurrence of new/worsened organ dysfunction during index hospitalization or death from any cause. 2) Improving clinical recovery: Hierarchical composite outcome measures including time to death from any cause through Day 30, new/worsened organ dysfunction, clinical status at day 30 and hospital discharge before Day 30 and alive at Day 30. | |
| In the report 1) A composite of time to new or worsened respiratory, cardiovascular, or kidney organ dysfunction during the index hospitalisation, or death from any cause at any time during the 30 day treatment period. 2) A hierarchical composite that ranked patients into categories using the severity and timing of events experienced during the 30 day treatment period: death, organ dysfunction during the index hospitalisation, supplemental oxygen requirement for patients hospitalised at day 30 without organ dysfunction, and hospital discharge before day 30. | |
| Documents available |
Protocol Yes. In English Statistical plan Yes Data-sharing stated
|
| Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review |
Low |
| General comment | In addition to the published article, the study registry, protocol, and statistical analysis plan were used in data extraction and risk of bias assessment. The study achieved the target sample size specified in the trial registry (n=1250). There were no substantive differences between the published article and the trial registry, protocol and statistical analysis plan in population. Procedures, interventions and outcomes. A protocol change occurred in Nov 2020, because "changes in the standard of care for patients hospitalised with COVID-19 resulted in substantially lower event rates than originally projected... faster and more complete recovery became an important treatment goal in addition to the prevention of complications and death, prompting the addition of recovery to the primary objectives on Nov 20, 2020". The primary outcomes reported reflect those in the registry. The article reports preliminary analyses of data from the 30 day treatment period, with data for an additional 60-day follow-up period to be published at later date. |