Dapagliflozin in Patients With Critical Illness (DEFENDER)

Hospital Israelita Albert Einstein

Status and phase: Completed; Phase 3

Conditions: Critical Illness; Sepsis

Treatments: Drug: Dapagliflozin 10mg Tab; Other: Standard of Care

Study type: Interventional

Funder types: Other

Identifiers

NCT05558098

DEFENDER

Details and patient eligibility

About

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

Full 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.

Enrollment: 507 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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507 participants in 2 patient groups

Standard of Care

Active Comparator group

Description:

Current standard of care for critically ill patients.

Treatment:

Other: Standard of Care

Standard of care plus dapagliflozin

Active Comparator group

Description:

Current standard of care for critically ill patients plus open-label dapagliflozin 10 mg per day for 14 days or until ICU discharge

Treatment:

Drug: Dapagliflozin 10mg Tab