Dapagliflozin in Patients With Critical Illness

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

Detailed Description
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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.

Official Title
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Dapagliflozin in Patients With Critical Illness: A Randomized Controlled Trial

Conditions
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Critical Illness, Sepsis

Intervention / Treatment
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* Drug: Dapagliflozin 10mg Tab
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Patients with at least one new organ dysfunction: 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); 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; Need for new use of high-flow nasal catheter or noninvasive ventilation or invasive ventilation. Exclusion Criteria: Pregnancy or age below 18 years; Patient or legal representative refusal; Patients with chronic kidney disease on dialysis; Planned intensive care unit admission after elective surgery; Known allergy to dapagliflozin; Previous use of dapagliflozin or other sodium-glucose transport protein 2 inhibitor; Patients that cannot receive medications through oral or enteral route; Patients with inclusion criteria number 2 for more than 24 hours. Patients with type 1 diabetes or previous ketoacidosis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of Care<br>Current standard of care for critically ill patients. | Other: Standard of Care<br>* Current standard of care for management of critically ill patients<br>|
| Active Comparator: Standard of care plus dapagliflozin<br>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<br>* Dapagliflozin 10 mg once per day for 14 days or until intensive care unit discharge or death<br>* Other names: Farxiga;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Win Ratio | Hierarchical endpoint of hospital mortality, use of kidney replacement therapy and intensive care unit length-of-stay | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital Mortality | Death within index hospitalization | 28 days | 
| Use of kidney replacement therapy | Use of kidney replacement therapy during hospital stay | 28 days | 
| Intensive Care Unit Free Days | Number of days patient was alive and not in the intensive care unit within index hospitalization | 28 days | 
| Hospital Free Days | Number of days patient was alive and not in the hospital | 28 days | 
| Vasopressor Free Days | Number of days patient was alive and not using vasopressors at any dose within index hospitalization | 28 days | 
| Mechanical Ventilation Free Days | Number of days patient was alive and not using mechanical ventilation within index hospitalization | 28 days | 
| Kidney Replacement Therapy Free Days | Number of days patient was alive and not using kidney replacement therapy within index hospitalization | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dapagliflozin, critical illness