Dapagliflozin in Patients With Critical Illness

Conditions

Critical Illness, Sepsis

Keywords

dapagliflozin, critical illness

Brief summary

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

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.

Tavares CAM, Azevedo LCP, Guimarães PO, Rea-Neto Á, David-João PG, Campos NS, Amendola CP, Kozesinski-Nakatani AC, Filiponi TC, Almeida GMB, Bergo RR, Lobo SM, Tognon AP, Tavares MS, Silveira FS, Dracoulakis MDA, Biondi RS, Monfardini F, Nieri J, Madrini V, Serpa-Neto A, Bacal F, Lemos PA, Berwanger O, Ezekowitz JA, Zampieri FG, DEFENDER Investigators.

2025-12-19

10.1016/j.jacadv.2025.102459

Dapagliflozin for Critically Ill Patients With Acute Organ Dysfunction

Caio A.M. Tavares, Luciano César Pontes Azevedo, Álvaro Réa-Neto, Niklas Söderberg Campos, Cristina Prata Amêndola et al. (100 authors)

JAMA2024-06-1442 citations

10.1001/jama.2024.10510

Dapagliflozin in patients with critical illness: rationale and design of the DEFENDER study.

Tavares CAM, Azevedo LCP, Rea-Neto Á, Campos NS, Amendola CP, Bergo RR, Kozesinski-Nakatani AC, David-João PG, Westphal GA, Guimarães Júnior MRR, Lobo SMA, Tavares MS, Dracoulakis MDA, Souza GM, Almeida GMB, Gebara OCE, Tomba PO, Albuquerque CSN, Silva MCR, Pereira AJ, Damiani LP, Corrêa TD, Serpa-Neto A, Berwanger O, Zampieri FG.

2023-12-222 citations

10.5935/2965-2774.20230129-en

Dapagliflozina em pacientes com doença crítica: justificativa e desenho do estudo DEFENDER

Caio de Assis Moura Tavares, Luciano César Pontes Azevedo, Álvaro Réa-Neto, Niklas Söderberg Campos, Cristina Prata Amêndola et al. (25 authors)

Critical Care Science2023-01-01

10.5935/2965-2774.20230129-pt

Interventions

DRUGDapagliflozin 10mg Tab

Dapagliflozin 10 mg once per day for 14 days or until intensive care unit discharge or death

OTHERStandard of Care

Current standard of care for management of critically ill patients

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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

Design outcomes

Primary

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

Secondary

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

Countries

Brazil

Outcome results

None listed