Dapagliflozin in Patients With Critical Illness (DEFENDER)

October 30, 2023 updated by: Hospital Israelita Albert Einstein

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
507

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Brazil
      • Barretos, Brazil
        • Santa Casa de Barretos
      • Curitiba, Brazil
        • Santa Casa de Curitiba
      • Jales, Brazil
        • Hospital de Amor de Jales
      • Joinville, Brazil
        • Unimed Joinville
      • Rio De Janeiro, Brazil
        • Hospital São Lucas de Copacabana
      • São Paulo, Brazil
        • Hospital Santa Paula
      • São Paulo, Brazil
        • Hospital Municipal Vila Santa Catarina
      • São Paulo, Brazil
        • Hospital M´Boi Mirim
    • Alagoas
      • Arapiraca, Alagoas, Brazil
        • Hospital de Emergência Dr. Daniel Houly
    • BA
      • Salvador, BA, Brazil
        • Instituto de Ensino e Pesquisa do Hospital da Bahia
    • DF
      • Brasilia, DF, Brazil
        • Hospital Brasilia
    • ES
      • Colatina, ES, Brazil
        • Hospital e Maternidade São José
    • GO
      • Aparecida De Goiânia, GO, Brazil
        • Hospital Municipal de Aparecida de Goiânia
    • MG
      • Poços De Caldas, MG, Brazil
        • Hospital Santa Lucía
    • Paraná
      • Curitiba, Paraná, Brazil
        • Hospital das Nações
      • Curitiba, Paraná, Brazil
        • Hospital Ecoville - Instituto de Neurologia de Curitiba
    • RS
      • Vacaria, RS, Brazil
        • Hospital Nossa Senhora da Oliveira
    • Rio Grande Do Sul
      • Passo Fundo, Rio Grande Do Sul, Brazil
        • Hospital São Vicente de Paulo
    • SC
      • Florianópolis, SC, Brazil
        • Hospital Baía Sul
    • SP
      • São José Do Rio Preto, SP, Brazil
        • Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto
      • São Paulo, SP, Brazil
        • Hospital Nove de Julho
    • Sergipe
      • Aracaju, Sergipe, Brazil, 49055-530
        • Centro de Pesquisa Clinica do Coracao
    • São Paulo
      • Barretos, São Paulo, Brazil
        • Hospital de Amor de Barretos

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Standard of Care
Current standard of care for critically ill patients.
Other: Standard of Care
Current standard of care for management of critically ill patients
Active Comparator: 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
Drug: Dapagliflozin 10mg Tab
Dapagliflozin 10 mg once per day for 14 days or until intensive care unit discharge or death
Other Names:
  • Farxiga

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Win Ratio
Time Frame: 28 days
Hierarchical endpoint of hospital mortality, use of kidney replacement therapy and intensive care unit length-of-stay
28 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Hospital Mortality
Time Frame: 28 days
Death within index hospitalization
28 days
Use of kidney replacement therapy
Time Frame: 28 days
Use of kidney replacement therapy during hospital stay
28 days
Intensive Care Unit Free Days
Time Frame: 28 days
Number of days patient was alive and not in the intensive care unit within index hospitalization
28 days
Hospital Free Days
Time Frame: 28 days
Number of days patient was alive and not in the hospital
28 days
Vasopressor Free Days
Time Frame: 28 days
Number of days patient was alive and not using vasopressors at any dose within index hospitalization
28 days
Mechanical Ventilation Free Days
Time Frame: 28 days
Number of days patient was alive and not using mechanical ventilation within index hospitalization
28 days
Kidney Replacement Therapy Free Days
Time Frame: 28 days
Number of days patient was alive and not using kidney replacement therapy within index hospitalization
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hospital Israelita Albert Einstein

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Otavio Berwanger, PhD, Academic Research Organization

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 20, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 20, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 23, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 23, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 28, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 31, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 30, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DEFENDER

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Data will be shared upon reasonable request after approval of the steering committee

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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