Clinical trial NCT05558098: Dapagliflozin in Patients With Critical Illness
Official title: Dapagliflozin in Patients With Critical Illness: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Critical Illness
Sepsis
Keywords: dapagliflozin
critical illness
Lead sponsor: Hospital Israelita Albert Einstein
Sponsor class: OTHER
First posted: 2022-09-28
Enrollment: 507
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Win Ratio
timeFrame: 28 days
Secondary outcomes:
measure: Hospital Mortality
timeFrame: 28 days
measure: Use of kidney replacement therapy
timeFrame: 28 days
measure: Intensive Care Unit Free Days
timeFrame: 28 days
measure: Hospital Free Days
timeFrame: 28 days
measure: Vasopressor Free Days
timeFrame: 28 days
measure: Mechanical Ventilation Free Days
timeFrame: 28 days
measure: Kidney Replacement Therapy Free Days
timeFrame: 28 days
Other outcomes:
Locations:
city: Arapiraca
country: Brazil
facility: Hospital de Emergência Dr. Daniel Houly
state: Alagoas
city: Salvador
country: Brazil
facility: Instituto de Ensino e Pesquisa do Hospital da Bahia
state: BA
city: Brasilia
country: Brazil
facility: Hospital Brasilia
state: DF
city: Colatina
country: Brazil
facility: Hospital e Maternidade São José
state: ES
city: Aparecida De Goiânia
country: Brazil
facility: Hospital Municipal de Aparecida de Goiânia
state: GO
city: Poços De Caldas
country: Brazil
facility: Hospital Santa Lucia
state: MG
city: Curitiba
country: Brazil
facility: Hospital das Nações
state: Paraná
city: Curitiba
country: Brazil
facility: Hospital Ecoville - Instituto de Neurologia de Curitiba
state: Paraná
city: Passo Fundo
country: Brazil
facility: Hospital São Vicente de Paulo
state: Rio Grande Do Sul
city: Vacaria
country: Brazil
facility: Hospital Nossa Senhora da Oliveira
state: RS
city: Florianópolis
country: Brazil
facility: Hospital Baia Sul
state: SC
city: Aracaju
country: Brazil
facility: Centro de Pesquisa Clínica do Coração
state: Sergipe
city: São José Do Rio Preto
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto
state: SP
city: São Paulo
country: Brazil
facility: Hospital Nove de Julho
state: SP
city: Barretos
country: Brazil
facility: Hospital de Amor de Barretos
state: São Paulo
city: Barretos
country: Brazil
facility: Santa Casa de Barretos
city: Curitiba
country: Brazil
facility: Santa Casa de Curitiba
city: Jales
country: Brazil
facility: Hospital de Amor de Jales
city: Joinville
country: Brazil
facility: Unimed Joinville
city: Rio De Janeiro
country: Brazil
facility: Hospital São Lucas de Copacabana
city: São Paulo
country: Brazil
facility: Hospital Municipal Vila Santa Catarina
city: São Paulo
country: Brazil
facility: Hospital M´Boi Mirim
city: São Paulo
country: Brazil
facility: Hospital Santa Paula
Study officials:
affiliation: Academic Research Organization
name: Otavio Berwanger, PhD
role: STUDY_CHAIR
References: