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

NCT05468203 | Terminated Phase 3 DMC

• 1 other identifier: GI-RM-7738
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 3

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.

Conditions

Acute Kidney Injury

Keywords

Kidney failure; Sodium Glucose cotransporter-2 inhibitors; Critically ill; Critical Care; ICU

Outcome Measures

Primary Outcomes (1)

• 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

  Within 30 days of randomisation

Secondary Outcomes (6)

• Doubling of Serum Creatinine

  Within 30 days of randomisation

• Requirement of Renal Replacement Therapy (RRT)

  Within 30 days of randomisation

• All-cause mortality

  Within 30 days of randomisation

• Vasoactive drug therapy

  Within 30 days of randomisation

• Mechanical ventilation

  Within 30 days of randomisation

Study Arms (2)

Dapagliflozin

EXPERIMENTAL

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

Drug: Dapagliflozin 10mg Tab

Matched Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Placebo DRUG

Patients will be randomly assigned to receive either dapagliflozin 10 mg or placebo daily while in ICU for up to 30 days

Matched Placebo

Dapagliflozin 10mg Tab DRUG

Patients will be randomly assigned to receive either dapagliflozin 10 mg or placebo daily while in ICU for up to 30 days

Also known as: SGLT2 inhibitor

Dapagliflozin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The George Institute: lead
• University Medical Center Groningen: collaborator
• Australian and New Zealand Intensive Care Society Clinical Trials Group: collaborator

Study Sites (3)

Grampians Health

Ballarat, Victoria, 3350, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Epworth Richmond

Richmond, Victoria, 3121, Australia

Location

MeSH Terms

Conditions

Acute Kidney Injury; Renal Insufficiency; Critical Illness

Interventions

dapagliflozin; Sodium-Glucose Transporter 2 Inhibitors

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs

Study Officials

• Martin P Gallagher, MBBS, FRACP

  The George Institute

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, international, multi-centre, double blinded, randomised controlled trial

Study Record Dates

• First Submitted: July 19, 2022
• First Posted: July 21, 2022
• Study Start: November 29, 2023
• Primary Completion: July 18, 2025
• Study Completion: December 23, 2025
• Last Updated: March 30, 2026

Record last verified: 2026-03

Locations

AU (3)