Dapagliflozin in Patients With Critical Illness

Sepsis Clinical Trial

— DEFENDER  

Official title:

Dapagliflozin in Patients With Critical Illness: A Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05558098
• Other study ID #: DEFENDER
• Status: Completed
• Phase: Phase 3
• Start date: November 1, 2022
• Est. completion date: October 20, 2023

Study information

• Verified date: October 2023
• Source: Hospital Israelita Albert Einstein
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Completed
• Enrollment: 507
• Est. completion date: October 20, 2023
• Est. primary completion date: October 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Critical Illness
• Sepsis

Intervention

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

Other:
• Standard of Care
Current standard of care for management of critically ill patients

Locations

Country	Name	City	State
Brazil	Hospital Municipal de Aparecida de Goiânia	Aparecida De Goiânia	GO
Brazil	Centro de Pesquisa Clínica do Coração	Aracaju	Sergipe
Brazil	Hospital de Emergência Dr. Daniel Houly	Arapiraca	Alagoas
Brazil	Hospital de Amor de Barretos	Barretos	São Paulo
Brazil	Santa Casa de Barretos	Barretos
Brazil	Hospital Brasilia	Brasilia	DF
Brazil	Hospital e Maternidade São José	Colatina	ES
Brazil	Hospital das Nações	Curitiba	Paraná
Brazil	Hospital Ecoville - Instituto de Neurologia de Curitiba	Curitiba	Paraná
Brazil	Santa Casa de Curitiba	Curitiba
Brazil	Hospital Baia Sul	Florianópolis	SC
Brazil	Hospital de Amor de Jales	Jales
Brazil	Unimed Joinville	Joinville
Brazil	Hospital São Vicente de Paulo	Passo Fundo	Rio Grande Do Sul
Brazil	Hospital Santa Lucia	Poços De Caldas	MG
Brazil	Hospital São Lucas de Copacabana	Rio De Janeiro
Brazil	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	Hospital M´Boi Mirim	São Paulo
Brazil	Hospital Municipal Vila Santa Catarina	São Paulo
Brazil	Hospital Nove de Julho	São Paulo	SP
Brazil	Hospital Santa Paula	São Paulo
Brazil	Hospital Nossa Senhora da Oliveira	Vacaria	RS

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Israelita Albert Einstein

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Win Ratio	Hierarchical endpoint of hospital mortality, use of kidney replacement therapy and intensive care unit length-of-stay	28 days
Secondary	Hospital Mortality	Death within index hospitalization	28 days
Secondary	Use of kidney replacement therapy	Use of kidney replacement therapy during hospital stay	28 days
Secondary	Intensive Care Unit Free Days	Number of days patient was alive and not in the intensive care unit within index hospitalization	28 days
Secondary	Hospital Free Days	Number of days patient was alive and not in the hospital	28 days
Secondary	Vasopressor Free Days	Number of days patient was alive and not using vasopressors at any dose within index hospitalization	28 days
Secondary	Mechanical Ventilation Free Days	Number of days patient was alive and not using mechanical ventilation within index hospitalization	28 days
Secondary	Kidney Replacement Therapy Free Days	Number of days patient was alive and not using kidney replacement therapy within index hospitalization	28 days