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Dapagliflozin in Patients With Critical Illness (DEFENDER)

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: NCT05558098
Recruitment Status : Completed
First Posted : September 28, 2022
Last Update Posted : October 31, 2023
Sponsor:
Information provided by (Responsible Party):
Hospital Israelita Albert Einstein

Study Description
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Brief Summary:
To assess the effects of dapagliflozin on a composite hierarchical endpoint in critically ill patients.

Condition or disease Intervention/treatment Phase
Critical Illness Sepsis Drug: Dapagliflozin 10mg Tab Other: Standard of Care Phase 3

Detailed Description:

Critically ill patients in the intensive care unit (ICU) experience a high mortality rate. Recent data indicates that the mortality rate for unplanned ICU admissions exceeds 30%, highlighting the urgent need for therapies that can reduce mortality in these critical patients.

DEFENDER is an investigator-initiated, multi-center, randomized, open-label clinical trial, conducted in Brazilian ICUs.

The study population will consist of participants who have been admitted to an ICU with an expected length of stay of more than 48 hours with evidence of at least an acute organ dysfunction, such as hypotension, signs of acute kidney injury, and/or the need for new use of high-flow nasal catheter, noninvasive or invasive ventilation. Eligible patients will be enrolled within 24 hours after the onset of organ dysfunction.

Participants will be randomly assigned in a 1:1 ratio to receive either dapagliflozin 10mg (for 14 days or until ICU discharge, whichever occurs sooner) in addition to standard of care, or standard care alone.

The primary outcome of the study is a hierarchical composite endpoint, including: i) hospital mortality, ii) initiation of kidney-replacement therapy, and iii) ICU length of stay. These outcomes will be assessed up to 28 days after randomization, with censoring at the time of hospital discharge.

To ensure participant safety, an independent Data and Safety Monitoring Board will periodically review the data.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 507 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Dapagliflozin in Patients With Critical Illness: A Randomized Controlled Trial
Actual Study Start Date : November 1, 2022
Actual Primary Completion Date : October 20, 2023
Actual Study Completion Date : October 20, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Standard of Care
Current standard of care for critically ill patients.
 Other: Standard of Care
Current standard of care for management of critically ill patients
Active Comparator: Standard of care plus dapagliflozin
Current standard of care for critically ill patients plus open-label dapagliflozin 10 mg per day for 14 days or until ICU discharge
 Drug: Dapagliflozin 10mg Tab
Dapagliflozin 10 mg once per day for 14 days or until intensive care unit discharge or death
Other Name: Farxiga


Outcome Measures
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Primary Outcome Measures :
  1. Win Ratio [ Time Frame: 28 days ]
    Hierarchical endpoint of hospital mortality, use of kidney replacement therapy and intensive care unit length-of-stay


Secondary Outcome Measures :
  1. Hospital Mortality [ Time Frame: 28 days ]
    Death within index hospitalization

  2. Use of kidney replacement therapy [ Time Frame: 28 days ]
    Use of kidney replacement therapy during hospital stay

  3. Intensive Care Unit Free Days [ Time Frame: 28 days ]
    Number of days patient was alive and not in the intensive care unit within index hospitalization

  4. Hospital Free Days [ Time Frame: 28 days ]
    Number of days patient was alive and not in the hospital

  5. Vasopressor Free Days [ Time Frame: 28 days ]
    Number of days patient was alive and not using vasopressors at any dose within index hospitalization

  6. Mechanical Ventilation Free Days [ Time Frame: 28 days ]
    Number of days patient was alive and not using mechanical ventilation within index hospitalization

  7. Kidney Replacement Therapy Free Days [ Time Frame: 28 days ]
    Number of days patient was alive and not using kidney replacement therapy within index hospitalization


Eligibility Criteria
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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. Patients admitted to an intensive care unit with expected duration of admission of at least 48 hours in the opinion of the attending physician AND

  2. Patients with at least one new organ dysfunction:

    1. Hypotension (mean arteria pressure below 65 mmHg or systolic blood pressure below 90 mmHg or use of vasopressors - norepinephrine, epinephrine, adrenaline, or vasopressin at any dose);
    2. Signs of acute kidney injury (increase in serum creatinine above 0.3 mg/dL over previous measurement or decrease in urinary output - below 0.5 mL/kg/h - in the past six hours;
    3. Need for new use of high-flow nasal catheter or noninvasive ventilation or invasive ventilation.

Exclusion Criteria:

  1. Pregnancy or age below 18 years;
  2. Patient or legal representative refusal;
  3. Patients with chronic kidney disease on dialysis;
  4. Planned intensive care unit admission after elective surgery;
  5. Known allergy to dapagliflozin;
  6. Previous use of dapagliflozin or other sodium-glucose transport protein 2 inhibitor;
  7. Patients that cannot receive medications through oral or enteral route;
  8. Patients with inclusion criteria number 2 for more than 24 hours.
  9. Patients with type 1 diabetes or previous ketoacidosis
Contacts and Locations
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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): NCT05558098


Locations
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Sponsors and Collaborators
Hospital Israelita Albert Einstein
Investigators
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Study Chair: Otavio Berwanger, PhD Academic Research Organization
More Information
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Responsible Party: Hospital Israelita Albert Einstein
ClinicalTrials.gov Identifier: NCT05558098    
Other Study ID Numbers: DEFENDER
First Posted: September 28, 2022    Key Record Dates
Last Update Posted: October 31, 2023
Last Verified: October 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Data will be shared upon reasonable request after approval of the steering committee

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hospital Israelita Albert Einstein:
dapagliflozin
critical illness
Additional relevant MeSH terms:
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Critical Illness
Disease Attributes
Pathologic Processes
Dapagliflozin
 Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs