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

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ClinicalTrials.gov Identifier: NCT04350593
Recruitment Status : Active, not recruiting
First Posted : April 17, 2020
Last Update Posted : May 12, 2021
Sponsor:
Collaborators:
Saint Luke's Hospital of Kansas City
AstraZeneca
George Clinical Pty Ltd
Information provided by (Responsible Party):
Saint Luke's Health System

Brief Summary:
This is an international, multicenter, parallel-group, randomized, double-blind, placebo controlled, study in hospitalized adult patients with COVID-19 in the US, Brazil, Mexico, Argentina, India, Canada, and UK. The study is evaluating the effect of dapagliflozin 10 mg 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.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: Dapagliflozin 10 MG Drug: Placebo Phase 3

Detailed Description:

COVID-19 can lead to multiorgan failure, especially in high-risk patients. Dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, favorably impacts many processes dysregulated during acute illness such as COVID-19, has significant cardio- and reno-protective benefits in cardiometabolic disease, and may provide similar organ protection in COVID-19.

The study population will include hospitalized patients with respiratory manifestations of COVID-19 of any duration, but without the need for mechanical ventilation. The eligible patients should have risk factors for developing serious complications of COVID-19, including hypertension, T2DM, ASCVD, HF and/or CKD stage 3 to 4.

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 dual primary efficacy endpoints of the study are time to first event of either complications or death from any cause, and improved clinical recovery through 30 days of follow-up. An extended follow-up period of 60 days (after the 30-day treatment period) is included, in order to examine longer-term trajectory of recovery from COVID-19 among trial participants.

The safety data will be monitored by an Independent Data and Safety Monitoring Committee.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : April 22, 2020
Actual Primary Completion Date : April 1, 2021
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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
Drug: Placebo
Placebo Comparator




Primary Outcome Measures :
  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. [ Time Frame: Randomization through Day 30 ]

    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 ECMO
    • 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
    • Doubling of s-Creatinine or initiation of renal replacement therapy

  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: [ Time Frame: Randomization through Day 30 ]
    1. Death from any cause through Day 30
    2. New/worsened organ dysfunction
    3. Clinical status at Day 30 for patients still hospitalized and without any worsening organ dysfunction
    4. Hospital discharge before Day 30 and alive at Day 30


Secondary Outcome Measures :
  1. Time to hospital discharge [ Time Frame: Randomization through Day 30 ]
    Time to hospital discharge

  2. Total number of days alive and free from respiratory decompensation requiring initiation of mechanical ventilation (includes invasive or non-invasive ventilation, CPAP, or BiPAP) [ Time Frame: Randomization through Day 30 ]
    Total number of days alive and free from respiratory decompensation requiring initiation of mechanical ventilation (includes invasive or non-invasive ventilation, CPAP, or BiPAP)

  3. 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) [ Time Frame: Randomization through Day 30 ]
    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)

  4. Time to composite of acute kidney injury or initiation of renal replacement therapy, or death from any cause [ Time Frame: Randomization through Day 30 ]
    Time to composite of acute kidney injury or initiation of renal replacement therapy, or death from any cause

  5. Time to death from any cause [ Time Frame: Randomization through Day 30 ]
    Time to death from any cause



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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 CT findings that, in the opinion of the investigator, are consistent with COVID-19
  7. 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. T2DM
    3. atherosclerotic cardiovascular disease
    4. heart failure (with either reduced or preserved LVEF)
    5. CKD stage 3 to 4 (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, CPAP, or 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 BP <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 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.

Information from the National Library of Medicine

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


Locations
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Sponsors and Collaborators
Saint Luke's Health System
Saint Luke's Hospital of Kansas City
AstraZeneca
George Clinical Pty Ltd
Investigators
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Study Chair: Mikhail Kosiborod, MD Saint Luke's Mid America Heart Institute
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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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 Posted: April 17, 2020    Key Record Dates
Last Update Posted: May 12, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Saint Luke's Health System:
SGLT2i
dapagliflozin
COVID-19
Additional relevant MeSH terms:
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Respiratory Insufficiency
Respiration Disorders
Respiratory Tract Diseases
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs