Dapagliflozin in Respiratory Failure in Patients With COVID-19 (DARE-19)
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|ClinicalTrials.gov Identifier: NCT04350593|
Recruitment Status : Recruiting
First Posted : April 17, 2020
Last Update Posted : April 17, 2020
|Condition or disease||Intervention/treatment||Phase|
|COVID-19||Drug: Dapagliflozin 10 MG Drug: Placebo||Phase 3|
Recent information on patients at risk for developing serious complications, including death, in the setting of COVID-19, indicate that those with cardiometabolic disease (hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and/or kidney disease at baseline) are at much greater risk (Arentz et al 2020, Grasselli et al 2020). Moreover, a large proportion of these patients develop cardiovascular complications; many have markedly elevated NT-proBNP levels, and a substantial proportion have evidence of acute myocardial injury and/or acute kidney injury. SGLT2i have previously been demonstrated to have potent heart and kidney-protective effects in patients with type 2 diabetes, heart failure and/or chronic kidney disease, and may afford protection of these vital organ systems in the setting of COVID-19. (Kosiborod et al 2017, McMurray et al 2019, Neal et al 2017, Perkovic et al 2019, Wiviott et al 2019, Zinman et al 2015).
Furthermore, both pre-clinical and clinical studies suggest that SGLT2i may favorably impact the underlying mechanistic processes dysregulated in the setting of acute major illness (such as COVID-19) and include favorable effects on energy metabolism, autophagy, oxidative stress, tissue hypoxia and inflammation (Ferrannini 2017, Aragón-Herrera 2019, Tanaka et al 2018, Packer 2020, Esterline et al 2018). These mechanisms have been shown to be important in the setting of respiratory failure, sepsis and multi-organ failure/cytokine storm.
The study population will include hospitalized patients with mild-moderate manifestations of COVID-19 of any duration, but without the need for mechanical ventilation at the time of screening. The eligible patients should have risk-factors for developing serious complications of COVID-19.
It will include patients with a history of at least one of the following: hypertension, T2DM, atherosclerotic cardiovascular disease, HF and/or CKD stage 3 to 4 (eGFR ≥25 mL/min/1.73m2).
Patients will be treated for 30 days, with either dapagliflozin 10 mg daily or placebo, each to be given in addition to the usual standard of care in the participating hospital.
The study assessments include only those that are absolutely critical for ensuring the safety of the patients, to measure efficacy outcomes, and collect biomarker data, so as not to place too high a burden on the study personnel and to minimize additional risk of exposure to SARS CoV-2.
The primary efficacy endpoint of the study is time to first event of all-cause death or morbid disease complications (respiratory, cardiovascular and kidney) through 30 days of follow-up.
The safety data will be monitored by an Independent Data and Safety Monitoring Committee.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||900 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||An International, Multicenter, Randomized, Double-blind, Placebo-controlled, Phase III Study Evaluating the Efficacy and Safety of Dapagliflozin in Respiratory Failure in Patients With COVID-19|
|Estimated Study Start Date :||April 15, 2020|
|Estimated Primary Completion Date :||October 2020|
|Estimated Study Completion Date :||December 2020|
Active Comparator: Dapagliflozin 10mg
Dapagliflozin 10 mg daily
Drug: Dapagliflozin 10 MG
Active Comparator: Dapagliflozin 10mg
Other Name: Farxiga
Placebo Comparator: Placebo
Dapagliflozin matching placebo 10 mg daily
- Time to first occurrence of either death from any cause or new/worsened organ dysfunction through 30 days of follow up, defined as at least one of the following: [ Time Frame: Randomization through Day 30 ]
- Respiratory decompensation
- New or worsening congestive HF
- 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
- Initiation of renal replacement therapy
- Hierarchical composite outcome measures: [ Time Frame: Randomization through Day 30 ]
- Time to death from any cause
- Time to new/worsened organ dysfunction (as defined in the primary outcome measure)
- Clinical status at Day 30 for patients still hospitalized and without any worsening organ dysfunction (using points 3 to 5 of a 7-point ordinal scale)
- Time to hospital discharge
- Time to hospital discharge [ Time Frame: Randomization through Day 30 ]Time to hospital discharge
- Total number of days alive, out of hospital, and/or free from mechanical ventilation [ Time Frame: Randomization through Day 30 ]Total number of days alive, out of hospital, and/or free from mechanical ventilation
- Total number of days alive, not in the ICU, and free from mechanical ventilation (as defined in the primary outcome measure) [ Time Frame: Randomization through Day 30 ]Total number of days alive, not in the ICU, and free from mechanical ventilation (as defined in the primary outcome measure)
- Time to death from any cause [ Time Frame: Randomization through Day 30 ]Time to death from any cause
- Time to new/worsened organ dysfunction [ Time Frame: Randomization through Day 30 ]Time to new/worsened organ dysfunction
- Time to acute kidney injury (defined as doubling of s-Creatinine compared to baseline) [ Time Frame: Randomization through Day 30 ]Time to acute kidney injury (defined as doubling of s-Creatinine compared to baseline)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04350593
|Contact: Sheryl Windsorfirstname.lastname@example.org|
|United States, Missouri|
|Saint Luke's Mid America Heart Institute||Recruiting|
|Kansas City, Missouri, United States, 64111|
|Contact: Study Coordinator 816-932-5989|
|Study Chair:||Mikhail Kosiborod, MD||Saint Luke's Mid America Heart Institute|