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

• ClinicalTrials.gov Identifier: NCT04350593
• Recruitment Status: Completed
• First Posted: April 17, 2020
• Results First Posted: April 13, 2022
• Last Update Posted: June 10, 2022
• Sponsor: Saint Luke's Health System
• Collaborators: Saint Luke's Hospital of Kansas City; AstraZeneca; George Clinical Pty Ltd
• Information provided by (Responsible Party): Saint Luke's Health System

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: COVID-19
• Interventions: Drug: Dapagliflozin 10 milligram (mg); Drug: Placebo
• Enrollment: 1250

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Dapagliflozin 10mg	Placebo
Arm/Group Description	Dapagliflozin 10 mg daily Dapagliflozin 10 MG: Active Comparator: Dapagliflozin 10mg	Dapagliflozin matching placebo 10 mg daily Placebo: Placebo Comparator
Period Title: Overall Study
Started	625	625
Completed	617	620
Not Completed	8	5

Baseline Characteristics

Arm/Group Title		Dapagliflozin 10mg	Placebo	Total
Arm/Group Description		Dapagliflozin 10 mg daily Dapagliflozin 10 MG: Active Comparator: Dapagliflozin 10mg	Dapagliflozin matching placebo 10 mg daily Placebo: Placebo Comparator	Total of all reporting groups
Overall Number of Baseline Participants		625	625	1250
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	625 participants	625 participants	1250 participants
		61.0 (13.4)	61.8 (13.5)	61.4 (13.5)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
	Female	260 41.6%	273 43.7%	533 42.6%
	Male	365 58.4%	352 56.3%	717 57.4%
Ethnicity (NIH/OMB) [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	621 participants	619 participants	1240 participants
	Hispanic or Latino	394 63.4%	362 58.5%	756 61.0%
	Not Hispanic or Latino	166 26.7%	177 28.6%	343 27.7%
	Unknown or Not Reported	61 9.8%	80 12.9%	141 11.4%
		[1] Measure Analysis Population Description: N numbers might differ for some parameters based on data availability.
Race (NIH/OMB) [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	623 participants	618 participants	1241 participants
	American Indian or Alaska Native	7 1.1%	10 1.6%	17 1.4%
	Asian	35 5.6%	29 4.7%	64 5.2%
	Native Hawaiian or Other Pacific Islander	1 0.2%	0 0.0%	1 0.1%
	Black or African American	85 13.6%	84 13.6%	169 13.6%
	White	452 72.6%	459 74.3%	911 73.4%
	More than one race	43 6.9%	36 5.8%	79 6.4%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
		[1] Measure Analysis Population Description: N numbers might differ for some parameters based on data availability.
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Canada	Number Analyzed	625 participants	625 participants	1250 participants
		2	2	4
Argentina	Number Analyzed	625 participants	625 participants	1250 participants
		13	14	27
United States	Number Analyzed	625 participants	625 participants	1250 participants
		143	144	287
Brazil	Number Analyzed	625 participants	625 participants	1250 participants
		382	380	762
United Kingdom	Number Analyzed	625 participants	625 participants	1250 participants
		0	2	2
Mexico	Number Analyzed	625 participants	625 participants	1250 participants
		59	59	118
India	Number Analyzed	625 participants	625 participants	1250 participants
		26	24	50
Type 2 diabetes; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		312 49.9%	324 51.8%	636 50.9%
Heart failure; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		44 7.0%	46 7.4%	90 7.2%
Hypertension; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		526 84.2%	534 85.4%	1060 84.8%
Atherosclerotic cardiovascular disease; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		93 14.9%	106 17.0%	199 15.9%
Chronic kidney disease, estimated glomerular filtration rate (eGFR) 25-60 mL/min per 1.73 m^2; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		38 6.1%	44 7.0%	82 6.6%
Patients with two or more inclusion risk factors; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		292 46.7%	319 51.0%	611 48.9%
Age >/= 60 years; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		339 54.2%	360 57.6%	699 55.9%
Body Mass Index >/= 30; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		296 47.4%	305 48.8%	601 48.1%
Chronic obstructive pulmonary disease; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		25 4.0%	32 5.1%	57 4.6%
Current smoker; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		29 4.6%	20 3.2%	49 3.9%
Heart rate; Mean (Standard Deviation); Unit of measure: Beats per minute
	Number Analyzed	625 participants	625 participants	1250 participants
		79.3 (13.7)	79.7 (13.7)	79.5 (13.7)
Blood pressure - systolic; Mean (Standard Deviation); Unit of measure: Mm Hg
	Number Analyzed	625 participants	625 participants	1250 participants
		126.6 (16.0)	127.0 (16.3)	126.8 (16.1)
Blood pressure - diastolic; Mean (Standard Deviation); Unit of measure: Mm Hg
	Number Analyzed	625 participants	625 participants	1250 participants
		76.6 (10.9)	76.2 (10.6)	76.4 (10.7)
Temperature; Mean (Standard Deviation); Unit of measure: Degrees Celcius
	Number Analyzed	625 participants	625 participants	1250 participants
		36.4 (0.6)	36.4 (0.7)	36.4 (0.6)
Oxygen saturation; Mean (Standard Deviation); Unit of measure: % (measured on supplemental oxygen)
	Number Analyzed	625 participants	625 participants	1250 participants
		95.5 (1.7)	95.2 (1.8)	95.3 (1.8)
eGFR; Mean (Standard Deviation); Unit of measure: mL/min per 1.73 m^2
	Number Analyzed	625 participants	625 participants	1250 participants
		84.1 (25.0)	83.4 (24.6)	83.8 (24.8)
SARS-CoV-2 test result at baseline; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
	Positive	584 93.4%	575 92.0%	1159 92.7%
	Negative	30 4.8%	35 5.6%	65 5.2%
	Test results not known	11 1.8%	15 2.4%	26 2.1%
Angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		225 36.0%	219 35.0%	444 35.5%
Beta-blocker; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		93 14.9%	98 15.7%	191 15.3%
Calcium blocker; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		84 13.4%	88 14.1%	172 13.8%
Loop-diuretic; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		49 7.8%	63 10.1%	112 9.0%
Statin; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		122 19.5%	144 23.0%	266 21.3%
Anti-coagulant; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		527 84.3%	527 84.3%	1054 84.3%
Biguanide; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		82 13.1%	75 12.0%	157 12.6%
Sulfonylurea; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		24 3.8%	22 3.5%	46 3.7%
Dipeptidyl peptidase 4 (DPP-4) inhibitor; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		17 2.7%	11 1.8%	28 2.2%
Glucagon-like peptide 1 (GLP-1) receptor agonist; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		6 1.0%	8 1.3%	14 1.1%
Insulin; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		223 35.7%	221 35.4%	444 35.5%
Remdesivir; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		114 18.2%	111 17.8%	225 18.0%
Systemic corticosteroids; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		176 28.2%	179 28.6%	355 28.4%
Dexamethasone; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		133 21.3%	136 21.8%	269 21.5%
Other systemic glucocorticoid; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	1250 participants
		50 8.0%	55 8.8%	105 8.4%

Outcome Measures

1. Primary Outcome

Title	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.
Description	Time to first occurrence of new/worsened organ dysfunction during index hospitalization or death from any cause. Event rates are presented as the number of subjects with event per 100 patient month (30 days) of follow-up. Unit of Measure: Patients with events per 100 patient-months (pt-mos) at risk. New/worsened organ dysfunction is defined as at least one of the following: Respiratory decompensation requiring initiation of mechanical ventilation (includes invasive or non-invasive ventilation, CPAP, or BiPAP), and/or initiation of extracorporeal membrane oxygenation (ECMO); New or worsening congestive heart failure; Requirement for vasopressor therapy and/or inotropic or mechanical circulatory support; Ventricular tachycardia or fibrillation lasting at least 30 seconds and/or associated with hemodynamic instability or pulseless electrical activity, or resuscitated cardiac arrest; Doubling of s-Creatinine or initiation of renal replacement therapy
Time Frame	Randomization through Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin 10mg	Placebo
Arm/Group Description:	Dapagliflozin 10 mg daily Dapagliflozin 10 MG: Active Comparator: Dapagliflozin 10mg	Dapagliflozin matching placebo 10 mg daily Placebo: Placebo Comparator
Overall Number of Participants Analyzed	625	625
Measure Type: Number; Unit of Measure: Patients with events/100 pt-mos at risk
	12.4	15.6

2. Primary Outcome

Title	Improving Clinical Recovery: Hierarchical Composite Outcome Measure Including 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.
Description	The number of patients experiencing improvement by day 30 compared with baseline (discharged from hospital without a worsening event and alive, or still in hospital without a worsening event and without oxygen support) in the hierarchical composite endpoint analysis. Hierarchical composite outcome measure includes: Death from any cause through Day 30; New/worsened organ dysfunction; Clinical status at Day 30 for patients still hospitalized and without any worsening organ dysfunction; Hospital discharge before Day 30 and alive at Day 30
Time Frame	Randomization through Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin 10mg	Placebo
Arm/Group Description:	Dapagliflozin 10 mg daily Dapagliflozin 10 MG: Active Comparator: Dapagliflozin 10mg	Dapagliflozin matching placebo 10 mg daily Placebo: Placebo Comparator
Overall Number of Participants Analyzed	625	625
Measure Type: Number; Unit of Measure: participants
	547	532

3. Secondary Outcome

Title	Time to Hospital Discharge
Description	Time to hospital discharge (refers to index hospitalization only). Median time to hospital discharge is presented in days.
Time Frame	Randomization through Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin 10mg	Placebo
Arm/Group Description:	Dapagliflozin 10 mg daily Dapagliflozin 10 MG: Active Comparator: Dapagliflozin 10mg	Dapagliflozin matching placebo 10 mg daily Placebo: Placebo Comparator
Overall Number of Participants Analyzed	625	625
Median (95% Confidence Interval); Unit of Measure: days
	5; (5.0 to 6.0)	6; (5.0 to 6.0)

4. Secondary Outcome

Title	Total Number of Days Alive and Free From Respiratory Decompensation Requiring Initiation of Mechanical Ventilation (Includes Invasive or Non-invasive Ventilation, CPAP, or BiPAP)
Description	Total number of days alive and free from mechanical ventilation (includes invasive or non-invasive ventilation, CPAP, or BiPAP) is calculated for each patient as total follow-up time (30 days) substracted days in hospital with mechanical ventilation and days dead.
Time Frame	Randomization through Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin 10mg	Placebo
Arm/Group Description:	Dapagliflozin 10 mg daily Dapagliflozin 10 MG: Active Comparator: Dapagliflozin 10mg	Dapagliflozin matching placebo 10 mg daily Placebo: Placebo Comparator
Overall Number of Participants Analyzed	625	625
Mean (Standard Deviation); Unit of Measure: days
	27.8 (6.8)	27.4 (7.4)

5. Secondary Outcome

Title	Total Number of Days Alive, Not in the ICU, and Free From Respiratory Decompensation Requiring Initiation of Mechanical Ventilation (Includes Invasive or Non-invasive Ventilation, CPAP, or BiPAP)
Description	Total number of days alive, not in the ICU and free from mechanical ventilation (includes invasive or non-invasive ventilation, CPAP, or BiPAP) is calculated for each patient as total follow-up time (30 days) substracted days in ICU and days dead.
Time Frame	Randomization through Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin 10mg	Placebo
Arm/Group Description:	Dapagliflozin 10 mg daily Dapagliflozin 10 MG: Active Comparator: Dapagliflozin 10mg	Dapagliflozin matching placebo 10 mg daily Placebo: Placebo Comparator
Overall Number of Participants Analyzed	625	625
Mean (Standard Deviation); Unit of Measure: days
	27.5 (7.2)	27.1 (7.7)

6. Secondary Outcome

Title	Time to Composite of Acute Kidney Injury or Initiation of Renal Replacement Therapy, or Death From Any Cause
Description	Acute kidney injury is defined as an episode of doubling s-creatinine compared to baseline during index hospitalization or SAE. Initiation of renal replacement therapy is defined as initiation of renal replacement therapy during index hospitalization or SAE. Event rates are presented as the number of subjects with event per 100 patient month (30 days) of follow-up. Unit of Measure: Patients with events per 100 patient-months (pt-mos) at risk.
Time Frame	Randomization through Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin 10mg	Placebo
Arm/Group Description:	Dapagliflozin 10 mg daily Dapagliflozin 10 MG: Active Comparator: Dapagliflozin 10mg	Dapagliflozin matching placebo 10 mg daily Placebo: Placebo Comparator
Overall Number of Participants Analyzed	625	625
Measure Type: Number; Unit of Measure: Patients with events/100 pt-mos at risk
	8.2	11.2

7. Secondary Outcome

Title	Time to Death From Any Cause
Description	Time to death from any cause. Event rates are presented as the number of subjects with event per 100 patient month (30 days) of follow-up. Unit of Measure: Patients with events per 100 patient-months (pt-mos) at risk.
Time Frame	Randomization through Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin 10mg	Placebo
Arm/Group Description:	Dapagliflozin 10 mg daily Dapagliflozin 10 MG: Active Comparator: Dapagliflozin 10mg	Dapagliflozin matching placebo 10 mg daily Placebo: Placebo Comparator
Overall Number of Participants Analyzed	625	625
Measure Type: Number; Unit of Measure: Patients with events/100 pt-mos at risk
	6.8	9.0

Adverse Events

Time Frame	Adverse events were collected from the time of signing informed consent through the end of the 30-day treatment period.
Adverse Event Reporting Description	All-cause mortality was monitored in the total started population of 1250 patients. Serious adverse events, adverse events resulting in the discontinuation of study drug, and safety events of acute kidney injury and diabetic ketoacidosis were monitored in the safety population defined as patients who received at least one dose of study medication. 613 patients in the dapagliflozin group and 616 patients in the placebo group received at least one dose of study medication.
Arm/Group Title	Dapagliflozin 10mg	Placebo
Arm/Group Description	Dapagliflozin 10 mg daily Dapagliflozin 10 MG: Active Comparator: Dapagliflozin 10mg	Dapagliflozin matching placebo 10 mg daily Placebo: Placebo Comparator
All-Cause Mortality
	Dapagliflozin 10mg	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	41/625 (6.56%)	54/625 (8.64%)
Serious Adverse Events
	Dapagliflozin 10mg	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	70/613 (11.42%)	87/616 (14.12%)
Blood and lymphatic system disorders
Anemia † 1	0/613 (0.00%)	1/616 (0.16%)
Cardiac disorders
Cardio-respiratory arrest † 1	3/613 (0.49%)	2/616 (0.32%)
Atrial fibrillation † 1	1/613 (0.16%)	2/616 (0.32%)
Cardiac failure † 1	1/613 (0.16%)	1/616 (0.16%)
Cardiac failure acute † 1	1/613 (0.16%)	0/616 (0.00%)
Acute myocardial infarction † 1	1/613 (0.16%)	1/616 (0.16%)
Cardiac arrest † 1	1/613 (0.16%)	1/616 (0.16%)
Cardiac failure congestive † 1	0/613 (0.00%)	1/616 (0.16%)
Myocardial infarction † 1	0/613 (0.00%)	1/616 (0.16%)
Cardiac Disorder † 1	1/613 (0.16%)	0/616 (0.00%)
Arrhythmia † 1	0/613 (0.00%)	1/616 (0.16%)
Gastrointestinal disorders
Abdominal pain † 1	1/613 (0.16%)	0/616 (0.00%)
Gastrointestinal hemorrhage † 1	1/613 (0.16%)	0/616 (0.00%)
Pancreatitis acute † 1	0/613 (0.00%)	1/616 (0.16%)
Upper gastrointestinal hemorrhage † 1	0/613 (0.00%)	1/616 (0.16%)
General disorders
Asthenia † 1	1/613 (0.16%)	1/616 (0.16%)
Multiple organ dysfunction syndrome † 1	3/613 (0.49%)	5/616 (0.81%)
General physical health deterioration † 1	0/613 (0.00%)	1/616 (0.16%)
Infections and infestations
COVID-19 † 1	5/613 (0.82%)	3/616 (0.49%)
Septic Shock † 1	5/613 (0.82%)	6/616 (0.97%)
Severe acute respiratory syndrome † 1	3/613 (0.49%)	3/616 (0.49%)
COVID-19 pneumonia † 1	1/613 (0.16%)	4/616 (0.65%)
Device related sepsis † 1	1/613 (0.16%)	0/616 (0.00%)
Emphysematous pyelonephritis † 1	1/613 (0.16%)	0/616 (0.00%)
Herpes virus infection † 1	1/613 (0.16%)	0/616 (0.00%)
Infection † 1	1/613 (0.16%)	1/616 (0.16%)
Meningoencephalitis herpetic † 1	1/613 (0.16%)	0/616 (0.00%)
Sepsis † 1	1/613 (0.16%)	3/616 (0.49%)
Labyrinthitis † 1	0/613 (0.00%)	1/616 (0.16%)
Pneumonia † 1	0/613 (0.00%)	8/616 (1.30%)
Pneumonia bacterial † 1	0/613 (0.00%)	2/616 (0.32%)
Pulmonary sepsis † 1	1/613 (0.16%)	1/616 (0.16%)
Urinary tract infection enterococcal † 1	0/613 (0.00%)	1/616 (0.16%)
Injury, poisoning and procedural complications
Femur fracture † 1	0/613 (0.00%)	1/616 (0.16%)
Rib fracture † 1	0/613 (0.00%)	1/616 (0.16%)
Investigations
Blood electrolytes abnormal † 1	1/613 (0.16%)	0/616 (0.00%)
Blood creatinine increased † 1	0/613 (0.00%)	1/616 (0.16%)
Metabolism and nutrition disorders
Lactic acidosis † 1	2/613 (0.33%)	0/616 (0.00%)
Diabetic ketoacidosis † 1	1/613 (0.16%)	0/616 (0.00%)
Diabetic metabolic decompensation † 1	1/613 (0.16%)	0/616 (0.00%)
Euglycemic diabetic ketoacidosis † 1	1/613 (0.16%)	0/616 (0.00%)
Hyperkalemia † 1	1/613 (0.16%)	0/616 (0.00%)
Metabolic acidosis † 1	1/613 (0.16%)	0/616 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Transitional cell carcinoma † 1	1/613 (0.16%)	0/616 (0.00%)
Prostate cancer † 1	0/613 (0.00%)	1/616 (0.16%)
Nervous system disorders
Ischemic stroke † 1	1/613 (0.16%)	0/616 (0.00%)
Myasthenia gravis † 1	1/613 (0.16%)	0/616 (0.00%)
Cerebral disorder † 1	0/613 (0.00%)	1/616 (0.16%)
Cerebrovascular accident † 1	0/613 (0.00%)	1/616 (0.16%)
Presnycope † 1	0/613 (0.00%)	1/616 (0.16%)
Syncope † 1	0/613 (0.00%)	1/616 (0.16%)
Psychiatric disorders
Psychotic disorder † 1	1/613 (0.16%)	0/616 (0.00%)
Renal and urinary disorders
Acute kidney injury † 1	21/613 (3.43%)	32/616 (5.19%)
Renal impairment † 1	1/613 (0.16%)	1/616 (0.16%)
Renal injury † 1	0/613 (0.00%)	2/616 (0.32%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure † 1	11/613 (1.79%)	11/616 (1.79%)
Acute respiratory failure † 1	4/613 (0.65%)	4/616 (0.65%)
Hypoxia † 1	3/613 (0.49%)	2/616 (0.32%)
Pulmonary embolism † 1	2/613 (0.33%)	2/616 (0.32%)
Respiration abnormal † 1	1/613 (0.16%)	0/616 (0.00%)
Chronic obstructive pulmonary disease † 1	0/613 (0.00%)	1/616 (0.16%)
Dyspnea † 1	0/613 (0.00%)	2/616 (0.32%)
Pneumothorax † 1	0/613 (0.00%)	1/616 (0.16%)
Pulmonary edema † 1	0/613 (0.00%)	2/616 (0.32%)
Respiratory distress † 1	0/613 (0.00%)	2/616 (0.32%)
Respiratory tract inflammation † 1	0/613 (0.00%)	1/616 (0.16%)
Vascular disorders
Arterial thrombosis † 1	1/613 (0.16%)	0/616 (0.00%)
Deep vein thrombosis † 1	1/613 (0.16%)	0/616 (0.00%)
Hemorrhage † 1	0/613 (0.00%)	1/616 (0.16%)
Hypovolemic shock † 1	1/613 (0.16%)	1/616 (0.16%)
Shock † 1	1/613 (0.16%)	2/616 (0.32%)
1 Term from vocabulary, MedDRA version 23.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Dapagliflozin 10mg	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	2/613 (0.33%)	2/616 (0.32%)
Renal and urinary disorders
Acute Kidney Injury † 1	2/613 (0.33%)	2/616 (0.32%)
1 Term from vocabulary, MedDRA version 23.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The sponsor can review results communications prior to public release and can embargo communications regarding results for a period that is less than or equal to 45 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication with the exception of requiring the removal of confidential information. The embargo can be extended to 90 days if there would be any patent applications to be filed by the sponsor related to the proposed publication.

Results Point of Contact

• Name/Title: DARE-19 Global Project Manager
• Organization: Saint Luke's Hospital of Kansas City
• Phone: 816-932-9858
• EMail: DARE-19@saint-lukes.org

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gasparyan SB, Buenconsejo J, Kowalewski EK, Oscarsson J, Bengtsson OF, Esterline R, Koch GG, Berwanger O, Kosiborod MN. Design and Analysis of Studies Based on Hierarchical Composite Endpoints: Insights from the DARE-19 Trial. Ther Innov Regul Sci. 2022 Sep;56(5):785-794. doi: 10.1007/s43441-022-00420-1. Epub 2022 Jun 14.

Kosiborod MN, Esterline R, Furtado RHM, Oscarsson J, Gasparyan SB, Koch GG, Martinez F, Mukhtar O, Verma S, Chopra V, Buenconsejo J, Langkilde AM, Ambery P, Tang F, Gosch K, Windsor SL, Akin EE, Soares RVP, Moia DDF, Aboudara M, Hoffmann Filho CR, Feitosa ADM, Fonseca A, Garla V, Gordon RA, Javaheri A, Jaeger CP, Leaes PE, Nassif M, Pursley M, Silveira FS, Barroso WKS, Lazcano Soto JR, Nigro Maia L, Berwanger O. Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2021 Sep;9(9):586-594. doi: 10.1016/S2213-8587(21)00180-7. Epub 2021 Jul 21.

• Responsible Party: Saint Luke's Health System
• ClinicalTrials.gov Identifier: NCT04350593
• Other Study ID Numbers: D1690C00081; ESR-20-20653 ( Other Grant/Funding Number: Astra Zeneca )
• First Submitted: April 14, 2020
• First Posted: April 17, 2020
• Results First Submitted: March 29, 2022
• Results First Posted: April 13, 2022
• Last Update Posted: June 10, 2022