Critical IllnessPhase 3DEFENDERNCT05558098
Dapagliflozin in Patients With Critical Illness
A Phase 3 study testing Dapagliflozin 10mg Tab in people with Critical Illness and Sepsis, run by Hospital Israelita Albert Einstein at 23 sites in Brazil.
Trial summary
To assess the effects of dapagliflozin on a composite hierarchical endpoint in critically ill patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critical Illness, Sepsis
- What is being tested?
- Dapagliflozin 10mg Tab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 507 participants
- Where
- 23 sitesBrazil
- Study dates
- 1 Nov 2022to 20 Oct 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 9Show fewer
- 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
Trial locations and contacts
23 sites in 1 country.
23 sites in 1 country
Brazil23 sites
Hospital Municipal de Aparecida de Goiânia
Aparecida de Goiânia, Goiás
Centro de Pesquisa Clínica do Coração
Aracaju, Sergipe, 49055-530
Hospital de Emergência Dr. Daniel Houly
Arapiraca, Alagoas
Hospital de Amor de Barretos
Barretos, São Paulo
Santa Casa de Barretos
Barretos
Hospital Brasilia
Brasília, Federal District
Hospital e Maternidade São José
Colatina, Espírito Santo
Hospital das Nações
Curitiba, Paraná
Hospital Ecoville - Instituto de Neurologia de Curitiba
Curitiba, Paraná
Santa Casa de Curitiba
Curitiba
Hospital Baia Sul
Florianópolis, Santa Catarina
Hospital de Amor de Jales
Jales
Unimed Joinville
Joinville
Hospital São Vicente de Paulo
Passo Fundo, Rio Grande do Sul
Hospital Santa Lucia
Poços de Caldas, Minas Gerais
Hospital São Lucas de Copacabana
Rio de Janeiro
Instituto de Ensino e Pesquisa do Hospital da Bahia
Salvador, Estado de Bahia
Fundação Faculdade Regional de Medicina de São José do Rio Preto
São José do Rio Preto, São Paulo
Hospital Nove de Julho
São Paulo, São Paulo
Hospital Municipal Vila Santa Catarina
São Paulo
Hospital M´Boi Mirim
São Paulo
Hospital Santa Paula
São Paulo
Hospital Nossa Senhora da Oliveira
Vacaria, Rio Grande do Sul
About this study
Official title: Dapagliflozin in Patients With Critical Illness: A Randomized Controlled Trial
To assess the effects of dapagliflozin on a composite hierarchical endpoint in critically ill patients.
Read the 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
- Being tested
- Dapagliflozin 10mg Tab, Standard of Care
- Keywords
- dapagliflozin, critical illness
- Medical subject headings
- Critical Illness, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dapagliflozin 10mg TabDrug
Also called Farxiga
Dapagliflozin 10 mg once per day for 14 days or until intensive care unit discharge or death
Standard of CareOther
Current standard of care for management of critically ill patients
| Study group | Role | What they receive |
|---|---|---|
| Standard of Care | Active comparator | Current standard of care for critically ill patients. Receives: Other: Standard of Care |
| Standard of care plus dapagliflozin | Active comparator | Current standard of care for critically ill patients plus open-label dapagliflozin 10 mg per day for 14 days or until ICU discharge Receives: Drug: Dapagliflozin 10mg Tab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Win Ratio
Hierarchical endpoint of hospital mortality, use of kidney replacement therapy and intensive care unit length-of-stay
Measured: 28 days
Secondary outcomes (7)
Hospital Mortality
Death within index hospitalization
Measured: 28 days
Use of kidney replacement therapy
Use of kidney replacement therapy during hospital stay
Measured: 28 days
Intensive Care Unit Free Days
Number of days patient was alive and not in the intensive care unit within index hospitalization
Measured: 28 days
Hospital Free Days
Number of days patient was alive and not in the hospital
Measured: 28 days
Vasopressor Free Days
Number of days patient was alive and not using vasopressors at any dose within index hospitalization
Measured: 28 days
Mechanical Ventilation Free Days
Number of days patient was alive and not using mechanical ventilation within index hospitalization
Measured: 28 days
Kidney Replacement Therapy Free Days
Number of days patient was alive and not using kidney replacement therapy within index hospitalization
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2022
- Study start1 Nov 2022
- Primary completion20 Oct 2023
- Study completion20 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Critical IllnessStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 507 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Israelita Albert Einstein
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Otavio Berwanger, PhD, Study chair, Academic Research Organization
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05558098
- Sponsor's protocol ID
- DEFENDER
- Acronym
- DEFENDER
- Status last verified
- Oct 2023
- First submitted
- 23 Sep 2022
- Last updated
- 31 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Data will be shared upon reasonable request after approval of the steering committee
Publications
Tavares CAM, Azevedo LCP, Guimaraes PO, Rea-Neto A, David-Joao 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 Jr, Serpa-Neto A, Bacal F, Lemos PA, Berwanger O, Ezekowitz JA, Zampieri FG; DEFENDER Investigators. Dapagliflozin in Acute Cardiovascular Conditions: Insights From the DEFENDER Trial. JACC Adv. 2026 Jan;5(1):102459. doi: 10.1016/j.jacadv.2025.102459. Epub 2025 Dec 19.
PubMed 41421016Tavares 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.
PubMed 38873723Tavares 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.
PubMed 38133155
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dapagliflozin in Patients With Critical Illness: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05558098
- Acronym / sponsor ID
- DEFENDER / DEFENDER
- Conditions
- Critical Illness, Sepsis
- Keywords
- dapagliflozin, critical illness
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 507 participants (actual)
- Lead sponsor
- Hospital Israelita Albert EinsteinUniversity, hospital or other
- Study start
- 1 Nov 2022 (actual)
- Primary completion
- 20 Oct 2023 (actual)
- Study completion
- 20 Oct 2023 (actual)
- First posted
- 28 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard of Care | Active comparator | Other: Standard of CareCurrent standard of care for critically ill patients. |
| Standard of care plus dapagliflozin | Active comparator | Drug: Dapagliflozin 10mg TabCurrent standard of care for critically ill patients plus open-label dapagliflozin 10 mg per day for 14 days or until ICU discharge |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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:
Key exclusion criteria (9 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dapagliflozin 10mg TabAlso: FarxigaDapagliflozin 10 mg once per day for 14 days or until intensive care unit discharge or death | Drug | Standard of care plus dapagliflozin |
| Standard of CareCurrent standard of care for management of critically ill patients | Other | Standard of Care |
Primary outcome
Win Ratio
Time frame: 28 days
Hierarchical endpoint of hospital mortality, use of kidney replacement therapy and intensive care unit length-of-stay
7 secondary outcomes
Hospital Mortality
Time frame: 28 days
Use of kidney replacement therapy
Time frame: 28 days
Intensive Care Unit Free Days
Time frame: 28 days
Hospital Free Days
Time frame: 28 days
Vasopressor Free Days
Time frame: 28 days
Mechanical Ventilation Free Days
Time frame: 28 days
Kidney Replacement Therapy Free Days
Time frame: 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2023.
- Derived from this study: PubMed 41421016Tavares CAM, Azevedo LCP, Guimaraes PO, Rea-Neto A, David-Joao 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 Jr, Serpa-Neto A, Bacal F, Lemos PA, Berwanger O, Ezekowitz JA, Zampieri FG; DEFENDER Investigators. Dapagliflozin in Acute Cardiovascular Conditions: Insights From the DEFENDER Trial. JACC Adv. 2026 Jan;5(1):102459. doi: 10.1016/j.jacadv.2025.102459. Epub 2025 Dec 19.
- Derived from this study: PubMed 38873723Tavares 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.
- Derived from this study: PubMed 38133155Tavares 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.
- Individual participant dataSharing planned: Undecided. Data will be shared upon reasonable request after approval of the steering committee
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Otavio Berwanger, PhD study chair
Academic Research Organization
23 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dapagliflozin 10mg Tab in people with Critical Illness and Sepsis, run by Hospital Israelita Albert Einstein at 23 sites in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Win Ratio (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05558098, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2023.