Dapagliflozin in Patients With Critical Illness

NCT ID: NCT05558098

Last Updated: 2023-10-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 507 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-01
• Study Completion Date: 2023-10-20

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.

Conditions

Critical Illness; Sepsis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard of Care

Current standard of care for critically ill patients.

Group Type: ACTIVE_COMPARATOR

Standard of Care

Intervention Type: OTHER

Current standard of care for management of critically ill patients

Standard of care plus dapagliflozin

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

Group Type: ACTIVE_COMPARATOR

Dapagliflozin 10mg Tab

Intervention Type: DRUG

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

Interventions

Dapagliflozin 10mg Tab

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

Intervention Type: DRUG

Standard of Care

Current standard of care for management of critically ill patients

Intervention Type: OTHER

Other Intervention Names

Farxiga

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.

9. Patients with type 1 diabetes or previous ketoacidosis

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;

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital Israelita Albert Einstein

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Otavio Berwanger, PhD

Role: STUDY_CHAIR

Academic Research Organization

Locations

Hospital de Emergência Dr. Daniel Houly

Arapiraca, Alagoas, Brazil

Hospital e Maternidade São José

Colatina, Espírito Santo, Brazil

Instituto de Ensino e Pesquisa do Hospital da Bahia

Salvador, Estado de Bahia, Brazil

Hospital Brasilia

Brasília, Federal District, Brazil

Hospital Municipal de Aparecida de Goiânia

Aparecida de Goiânia, Goiás, Brazil

Hospital Santa Lucia

Poços de Caldas, Minas Gerais, Brazil

Hospital das Nações

Curitiba, Paraná, Brazil

Hospital Ecoville - Instituto de Neurologia de Curitiba

Curitiba, Paraná, Brazil

Hospital São Vicente de Paulo

Passo Fundo, Rio Grande do Sul, Brazil

Hospital Nossa Senhora da Oliveira

Vacaria, Rio Grande do Sul, Brazil

Hospital Baia Sul

Florianópolis, Santa Catarina, Brazil

Centro de Pesquisa Clínica do Coração

Aracaju, Sergipe, Brazil

Hospital de Amor de Barretos

Barretos, São Paulo, Brazil

Fundação Faculdade Regional de Medicina de São José do Rio Preto

São José do Rio Preto, São Paulo, Brazil

Hospital Nove de Julho

São Paulo, São Paulo, Brazil

Santa Casa de Barretos

Barretos, , Brazil

Santa Casa de Curitiba

Curitiba, , Brazil

Hospital de Amor de Jales

Jales, , Brazil

Unimed Joinville

Joinville, , Brazil

Hospital São Lucas de Copacabana

Rio de Janeiro, , Brazil

Hospital Municipal Vila Santa Catarina

São Paulo, , Brazil

Hospital M´Boi Mirim

São Paulo, , Brazil

Hospital Santa Paula

São Paulo, , Brazil

Countries

Brazil

References

Tavares CAM, Azevedo LCP, Rea-Neto A, Campos NS, Amendola CP, Kozesinski-Nakatani AC, David-Joao PG, Lobo SM, Filiponi TC, Almeida GMB, Bergo RR, Guimaraes-Junior MRR, Figueiredo RC, Castro JR, Schuler CJ, Westphal GA, Carioca ACR, Monfradini F, Nieri J, Neves FMO, Paulo JA, Albuquerque CSN, Silva MCR, Kosiborod MN, Pereira AJ, Damiani LP, Correa TD, Serpa-Neto A, Berwanger O, Zampieri FG; DEFENDER Investigators. Dapagliflozin for Critically Ill Patients With Acute Organ Dysfunction: The DEFENDER Randomized Clinical Trial. JAMA. 2024 Aug 6;332(5):401-411. doi: 10.1001/jama.2024.10510.

Reference Type: DERIVED

PMID: 38873723 (View on PubMed)

Tavares CAM, Azevedo LCP, Rea-Neto A, Campos NS, Amendola CP, Bergo RR, Kozesinski-Nakatani AC, David-Joao PG, Westphal GA, Guimaraes Junior MRR, Lobo SMA, Tavares MS, Dracoulakis MDA, Souza GM, Almeida GMB, Gebara OCE, Tomba PO, Albuquerque CSN, Silva MCR, Pereira AJ, Damiani LP, Correa TD, Serpa-Neto A, Berwanger O, Zampieri FG. Dapagliflozin in patients with critical illness: rationale and design of the DEFENDER study. Crit Care Sci. 2023 Dec 22;35(3):256-265. doi: 10.5935/2965-2774.20230129-en. eCollection 2023.

Reference Type: DERIVED

PMID: 38133155 (View on PubMed)

Other Identifiers

DEFENDER

Identifier Type: -

Identifier Source: org_study_id