Dapagliflozin in Patients With Critical Illness
- Conditions
- Critical IllnessSepsis
- Interventions
- Other: Standard of Care
- Registration Number
- NCT05558098
- Lead Sponsor
- Hospital Israelita Albert Einstein
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 507
-
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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard of care plus dapagliflozin Dapagliflozin 10mg Tab Current standard of care for critically ill patients plus open-label dapagliflozin 10 mg per day for 14 days or until ICU discharge Standard of Care Standard of Care Current standard of care for critically ill patients.
- Primary Outcome Measures
Name Time Method Win Ratio 28 days Hierarchical endpoint of hospital mortality, use of kidney replacement therapy and intensive care unit length-of-stay
- Secondary Outcome Measures
Name Time Method Hospital Mortality 28 days Death within index hospitalization
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
Vasopressor Free Days 28 days Number of days patient was alive and not using vasopressors at any dose 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
Trial Locations
- Locations (23)
Instituto de Ensino e Pesquisa do Hospital da Bahia
🇧🇷Salvador, BA, Brazil
Fundação Faculdade Regional de Medicina de São José do Rio Preto
🇧🇷São José Do Rio Preto, SP, Brazil
Unimed Joinville
🇧🇷Joinville, Brazil
Hospital Baia Sul
🇧🇷Florianópolis, SC, Brazil
Santa Casa de Barretos
🇧🇷Barretos, Brazil
Santa Casa de Curitiba
🇧🇷Curitiba, Brazil
Hospital São Lucas de Copacabana
🇧🇷Rio De Janeiro, Brazil
Hospital Municipal Vila Santa Catarina
🇧🇷São Paulo, Brazil
Hospital de Emergência Dr. Daniel Houly
🇧🇷Arapiraca, Alagoas, Brazil
Centro de Pesquisa ClÃnica do Coração
🇧🇷Aracaju, Sergipe, Brazil
Hospital Ecoville - Instituto de Neurologia de Curitiba
🇧🇷Curitiba, Paraná, Brazil
Hospital das Nações
🇧🇷Curitiba, Paraná, Brazil
Hospital e Maternidade São José
🇧🇷Colatina, ES, Brazil
Hospital Municipal de Aparecida de Goiânia
🇧🇷Aparecida De Goiânia, GO, Brazil
Hospital Brasilia
🇧🇷Brasilia, DF, Brazil
Hospital Nossa Senhora da Oliveira
🇧🇷Vacaria, RS, Brazil
Hospital Nove de Julho
🇧🇷São Paulo, SP, Brazil
Hospital de Amor de Jales
🇧🇷Jales, Brazil
Hospital M´Boi Mirim
🇧🇷São Paulo, Brazil
Hospital Santa Paula
🇧🇷São Paulo, Brazil
Hospital Santa Lucia
🇧🇷Poços De Caldas, MG, Brazil
Hospital São Vicente de Paulo
🇧🇷Passo Fundo, Rio Grande Do Sul, Brazil
Hospital de Amor de Barretos
🇧🇷Barretos, São Paulo, Brazil