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PREVENTion With Sglt-2 Inhibition of Acute Kidney Injury in Intensive Care (PREVENTS-AKI)

Primary Purpose

Acute Kidney Injury

Status
Not yet recruiting
Phase
Phase 3
Locations
Australia
Study Type
Interventional
Intervention
Dapagliflozin 10mg Tab
Placebo
Sponsored by
The George Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Acute Kidney Injury focused on measuring Kidney failure, Sodium Glucose cotransporter-2 inhibitors, Critically ill, Critical Care, ICU

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age 18 years or more
  • Admitted to ICU within the last 7 days
  • Expected to be in the ICU the day after tomorrow
  • An arterial or central venous catheter is in situ, or placement is planned for routine management
  • Able to receive study treatment orally or via enteral route

  • At least one of the following risk factors for AKI:

    • Required fluid resuscitation, defined as a bolus of fluid prescribed to be given over ≤1 hour to increase or maintain intravascular volume that is in addition to maintenance fluids
    • Being treated with continuous vasopressors or inotropes to maintain a systolic blood pressure > 90mmHg, or mean arterial blood pressure > 60mmHg or a MAP target set by the treating clinician for maintaining perfusion

  • At least one of the following pre-morbid risk factors:

    • Treatment for high blood pressure
    • Treatment for type 2 diabetes (minimum diet therapy)
    • Atherosclerotic cardiovascular disease
    • History of heart failure
    • Impaired renal function, defined as an eGFR between 20 - 60 mL/min/1.73m2
    • Estimated BMI 30 kg/m2 or more
    • Age 60 years or more

Exclusion Criteria:

  • Met all inclusion criteria more than 24 hours ago
  • History of type 1 diabetes mellitus or diabetic ketoacidosis
  • Requiring renal replacement therapy for intoxication
  • Known hypersensitivity to any SGLT-2 inhibitor e.g. dapagliflozin, canagliflozin, empagliflozin, ertugliflozin
  • Solid organ transplantation within the last 12 months
  • Likely to be transferred to another hospital in the next 3 days
  • Known or suspected pregnancy
  • Death is deemed imminent or inevitable
  • Life expectancy is estimated to be less than 90 days
  • Patient or the treating clinician declines to participate
  • Enrolled in another interventional trial for which co-enrolment is not approved
  • Patient has previously been enrolled in the PREVENTS-AKI Study

Sites / Locations

  • Grampians Health
  • Austin Health

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Dapagliflozin

Matched Placebo

Arm Description

Dapaliflozin 10mg tablet administered once daily while in ICU for up to 30 days

Matched placebo tablet administered once daily while in ICU for up to 30 days

Outcomes

Primary Outcome Measures

Composite outcome: Doubling of serum creatinine from baseline, initiation of renal replacement therapy or death
Proportion of patients experiencing a component of the composite outcome, defined as a doubling of serum creatinine from the study baseline value, initiation of RRT or death

Secondary Outcome Measures

Doubling of Serum Creatinine
Proportion of patients with a doubling of serum creatinine from baseline value
Requirement of Renal Replacement Therapy (RRT)
Proportion of patients requiring RRT
All-cause mortality
Proportion of patients who have died from any cause
Vasoactive drug therapy
Proportion of patients who were treated with vasoactive drugs
Mechanical ventilation
Proportion of patients who required mechanical ventilation
Ventricular tachycardia or ventricular fibrillation
Proportion of patients who experienced ventricular tachycardia or ventricular fibrillation lasting at least 30 seconds whilst in intensive care

Full Information

First Posted
July 19, 2022
Last Updated
August 13, 2023
Sponsor
The George Institute
Collaborators
University Medical Center Groningen, Australian and New Zealand Intensive Care Society Clinical Trials Group
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1. Study Identification

Unique Protocol Identification Number
NCT05468203
Brief Title
PREVENTion With Sglt-2 Inhibition of Acute Kidney Injury in Intensive Care
Acronym
PREVENTS-AKI
Official Title
PREVENTion With Sglt-2 Inhibition of Acute Kidney Injury in Intensive Care
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 1, 2023 (Anticipated)
Primary Completion Date
August 31, 2026 (Anticipated)
Study Completion Date
March 1, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The George Institute
Collaborators
University Medical Center Groningen, Australian and New Zealand Intensive Care Society Clinical Trials Group

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Background Acute Kidney Injury (AKI) is a potentially life-threatening condition caused by unsafe levels of fluid and waste products accumulating in the body. Often, patients with AKI need treatment with an artificial kidney (called renal replacement therapy or dialysis) to do the work of their kidneys and remove these dangerous levels of fluid and waste from the body. If left untreated, AKI can become a chronic (long-term) condition that may require treatment for life. Dapagliflozin is a medication used to treat patients with diabetes, heart disease and long-term (chronic) kidney disease. Recently, Dapagliflozin has been shown to slow the progression of other kidney related complications, however this has not yet been studied in critically ill patients. Aim To determine if giving Dapagliflozin (one tablet a day) compared to placebo (a tablet that looks identical but has no active ingredients), decreases injury to the kidneys in patients admitted to the Intensive Care Unit. Design This study will enrol 3000 patients from 45-50 hospitals worldwide. It is a 'randomised controlled trial' meaning patients will be randomly assigned (like tossing a coin) by a computer to receive either Dapagliflozin or placebo for a maximum of 30 days whilst in the ICU. The study is also a 'double blinded trial' meaning that neither the doctor, the intensive care staff or the patient will know which study treatment they are receiving.
Detailed Description
Acute kidney injury (AKI) is an increasingly common complication of hospitalisation globally, and a major driver of poor patient outcomes, including higher mortality and reduced quality of life. While numerous studies, including several led by investigators in this grant team, have tested treatments to reduce the impact of AKI, none have been shown to improve outcomes. The absence of any proven therapy highlights a critical unmet need. A novel class of medicines, inhibitors of the sodium-glucose co-transporter II (SGLT-2 inhibitors), have been shown in recent years to have dramatic effects upon cardiovascular and renal outcomes in patients with heart failure at high risk for renal failure. The evidence suggests that these drugs might prevent AKI from occurring, but this has not been intentionally tested in adequately powered trials. A recently published randomised controlled trial evaluated the use of these drugs in acutely unwell COVID-19 patients and did not raise any safety concern in this acute setting. The trial also showed a numerically lower rate of AKI in those that received the SGLT-2 inhibitor dapagliflozin compared to placebo, but the trial was not sufficiently powered for this outcome. The PREVENTion with Sglt2 inhibition of Acute Kidney Injury in intensive care (PREVENTS-AKI) trial, will test the effect of dapagliflozin versus placebo upon patients' risk of developing severe AKI in a population admitted to intensive care. This global trial will test the most promising treatment for mitigating the increased risk of AKI. The results will provide the first definitive insight into the prevention of AKI with these agents and will shape global clinical practice in an area where treatments are profoundly lacking.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Kidney Injury
Keywords
Kidney failure, Sodium Glucose cotransporter-2 inhibitors, Critically ill, Critical Care, ICU

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Prospective, international, multi-centre, double blinded, randomised controlled trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double-blinded
Allocation
Randomized
Enrollment
3000 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dapagliflozin
Arm Type
Experimental
Arm Description
Dapaliflozin 10mg tablet administered once daily while in ICU for up to 30 days
Arm Title
Matched Placebo
Arm Type
Placebo Comparator
Arm Description
Matched placebo tablet administered once daily while in ICU for up to 30 days
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin 10mg Tab
Other Intervention Name(s)
SGLT2 inhibitor
Intervention Description
Patients will be randomly assigned to receive either dapagliflozin 10 mg or placebo daily while in ICU for up to 30 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Patients will be randomly assigned to receive either dapagliflozin 10 mg or placebo daily while in ICU for up to 30 days
Primary Outcome Measure Information:
Title
Composite outcome: Doubling of serum creatinine from baseline, initiation of renal replacement therapy or death
Description
Proportion of patients experiencing a component of the composite outcome, defined as a doubling of serum creatinine from the study baseline value, initiation of RRT or death
Time Frame
Within 30 days of randomisation
Secondary Outcome Measure Information:
Title
Doubling of Serum Creatinine
Description
Proportion of patients with a doubling of serum creatinine from baseline value
Time Frame
Within 30 days of randomisation
Title
Requirement of Renal Replacement Therapy (RRT)
Description
Proportion of patients requiring RRT
Time Frame
Within 30 days of randomisation
Title
All-cause mortality
Description
Proportion of patients who have died from any cause
Time Frame
Within 30 days of randomisation
Title
Vasoactive drug therapy
Description
Proportion of patients who were treated with vasoactive drugs
Time Frame
Within 30 days of randomisation
Title
Mechanical ventilation
Description
Proportion of patients who required mechanical ventilation
Time Frame
Within 30 days of randomisation
Title
Ventricular tachycardia or ventricular fibrillation
Description
Proportion of patients who experienced ventricular tachycardia or ventricular fibrillation lasting at least 30 seconds whilst in intensive care
Time Frame
Within 30 days of randomisation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18 years or more Admitted to ICU within the last 7 days Expected to be in the ICU the day after tomorrow An arterial or central venous catheter is in situ, or placement is planned for routine management Able to receive study treatment orally or via enteral route At least one of the following risk factors for AKI: Required fluid resuscitation, defined as a bolus of fluid prescribed to be given over ≤1 hour to increase or maintain intravascular volume that is in addition to maintenance fluids Being treated with continuous vasopressors or inotropes to maintain a systolic blood pressure > 90mmHg, or mean arterial blood pressure > 60mmHg or a MAP target set by the treating clinician for maintaining perfusion At least one of the following pre-morbid risk factors: Treatment for high blood pressure Treatment for type 2 diabetes (minimum diet therapy) Atherosclerotic cardiovascular disease History of heart failure Impaired renal function, defined as an eGFR between 20 - 60 mL/min/1.73m2 Estimated BMI 30 kg/m2 or more Age 60 years or more Exclusion Criteria: Met all inclusion criteria more than 24 hours ago History of type 1 diabetes mellitus or diabetic ketoacidosis COVID-19 infection as the reason for ICU admission Requiring renal replacement therapy for intoxication eGFR less than 20 mL/min/1.73m2 Known hypersensitivity to any SGLT-2 inhibitor e.g. dapagliflozin, canagliflozin, empagliflozin, ertugliflozin Solid organ transplantation within the last 12 months Likely to be transferred to another hospital in the next 3 days Known or suspected pregnancy Death is deemed imminent or inevitable Life expectancy is estimated to be less than 90 days Patient or the treating clinician declines to participate Enrolled in another interventional trial for which co-enrolment is not approved Patient has previously been enrolled in the PREVENTS-AKI Study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sarah Coggan, BSc, MPH
Phone
02 9993 4566
Email
scoggan@georgeinstitute.org.au
First Name & Middle Initial & Last Name or Official Title & Degree
Sharon Micallef, BN
Email
smicallef@georgeinstitute.org.au
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Martin P Gallagher, MBBS, FRACP
Organizational Affiliation
The George Institute
Official's Role
Study Director
Facility Information:
Facility Name
Grampians Health
City
Ballarat
State/Province
Victoria
ZIP/Postal Code
3350
Country
Australia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Khaled El-Khawas, Dr
First Name & Middle Initial & Last Name & Degree
Khaled El-Khawas
Facility Name
Austin Health
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rinaldo Bellomo, Prof
First Name & Middle Initial & Last Name & Degree
Rinaldo Bellomo

12. IPD Sharing Statement

Learn more about this trial

PREVENTion With Sglt-2 Inhibition of Acute Kidney Injury in Intensive Care

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