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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE April 14, 2020
First Posted Date  ICMJE April 17, 2020
Last Update Posted Date May 12, 2021
Actual Study Start Date  ICMJE April 22, 2020
Actual Primary Completion Date April 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 25, 2021)
  • 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
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: April 14, 2020)
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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 25, 2021)
  • Time to hospital discharge [ Time Frame: Randomization through Day 30 ]
    Time to hospital discharge
  • 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)
  • 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)
  • 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
  • Time to death from any cause [ Time Frame: Randomization through Day 30 ]
    Time to death from any cause
Original Secondary Outcome Measures  ICMJE
 (submitted: April 14, 2020)
  • Hierarchical composite outcome measures: [ Time Frame: Randomization through Day 30 ]
    1. Time to death from any cause
    2. Time to new/worsened organ dysfunction (as defined in the primary outcome measure)
    3. 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)
    4. 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)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dapagliflozin in Respiratory Failure in Patients With COVID-19
Official Title  ICMJE 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
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE COVID-19
Intervention  ICMJE
  • Drug: Dapagliflozin 10 MG
    Active Comparator: Dapagliflozin 10mg
    Other Name: Farxiga
  • Drug: Placebo
    Placebo Comparator
Study Arms  ICMJE
  • Active Comparator: Dapagliflozin 10mg
    Dapagliflozin 10 mg daily
    Intervention: Drug: Dapagliflozin 10 MG
  • Placebo Comparator: Placebo
    Dapagliflozin matching placebo 10 mg daily
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 25, 2021)
1250
Original Estimated Enrollment  ICMJE
 (submitted: April 14, 2020)
900
Estimated Study Completion Date  ICMJE June 2021
Actual Primary Completion Date April 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Brazil,   Canada,   India,   Mexico,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04350593
Other Study ID Numbers  ICMJE D1690C00081
ESR-20-20653 ( Other Grant/Funding Number: Astra Zeneca )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Saint Luke's Health System
Study Sponsor  ICMJE Saint Luke's Health System
Collaborators  ICMJE
  • Saint Luke's Hospital of Kansas City
  • AstraZeneca
  • George Clinical Pty Ltd
Investigators  ICMJE
Study Chair: Mikhail Kosiborod, MD Saint Luke's Mid America Heart Institute
PRS Account Saint Luke's Health System
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP