Standard vs. Accelerated Initiation of RRT in Acute Kidney Injury (STARRT-AKI: Principal Trial)

Not Applicable

Completed

• Conditions: Acute Kidney Injury

• Registration Number: NCT02568722
• Lead Sponsor: Unity Health Toronto

Brief Summary

The objectives of this trial are to determine whether, in critically ill patients with severe acute kidney injury (AKI), randomization to accelerated initiation of renal replacement therapy (RRT), compared to standard initiation, leads to:

1. Improved survival (primary outcome); and

2. Recovery of kidney function (principal secondary outcome), defined as independence from RRT at 90 days

Detailed Description

Acute kidney injury (AKI) is a common and devastating complication of critical illness. Once AKI is established, treatment is largely supportive and no intervention has been found to restore kidney function or improve overall survival. Renal replacement therapy (RRT), usually in the form of hemodialysis, is frequently needed to manage patients with severe AKI. Such patients have an in-hospital mortality that consistently exceeds 50% with delays in RRT initiation implicated as a possible contributor. A recent meta-analysis suggested that earlier initiation of RRT may improve survival, but this is based on data derived overwhelmingly from observational studies. The investigators recently completed a multi-centre randomized controlled pilot trial that confirmed the feasibility of allocating patients to two different strategies of RRT initiation. Patient recruitment and follow-up, as well as patient safety, were successfully demonstrated during the pilot phase of this research program. The optimal timing of RRT initiation is an existing knowledge gap and a clear priority for investigation.

Study Timeline

• Study First Submitted: 2015-09-29
• Study Start: 2015-10
• Study First Submitted QC: 2015-10-04
• Study First Posted: 2015-10-06
• Primary Completion: 2019-12
• Study Completion: 2019-12
• Results First Submitted: 2023-02-15
• Status Verified: 2024-07
• Results First Submitted QC: 2024-07-27
• Last Update Submitted: 2024-07-27
• Results First Posted: 2024-10-18
• Last Update Posted: 2024-10-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 3019

Inclusion Criteria

1. Age ≥ 18 years

2. Admission to an intensive care unit (ICU)

3. Evidence of kidney dysfunction [serum creatinine ≥100 µmol/L (women) and ≥ 130 µmol/L (men)]

4. Evidence of severe AKI defined by at least 1 of the following 3 criteria:

   i) ≥ 2-fold increase in serum creatinine from a known pre-morbid baseline or during the current hospitalization; OR ii) Achievement of a serum creatinine ≥ 354 µmol/L with evidence of a minimum increase of 27 µmol/L from pre-morbid baseline or during the current hospitalization; OR iii) Urine output < 6.0 mL/kg over the preceding 12 hours

Exclusion Criteria

1. Serum potassium > 5.5 mmol/L

2. Serum bicarbonate < 15 mmol/L

3. Presence of a drug overdose that necessitates initiation of RRT

4. Lack of commitment to ongoing life support (including RRT)

5. Any RRT within the previous 2 months (either acute or chronic RRT)

6. Kidney transplant within the past 365 days

7. Known pre-hospitalization advanced chronic kidney disease, defined by an estimated glomerular filtration rate < 20 mL/min/1.73 m2

8. Presence or clinical suspicion of renal obstruction, rapidly progressive glomerulonephritis, vasculitis, thrombotic microangiopathy or acute interstitial nephritis

9. Clinician(s) caring for patient believe(s) that immediate RRT is mandated

10. Clinician(s) caring for patient believe(s) that deferral of RRT initiation is mandated

    • at their discretion, clinicians may administer a bolus of intravenous furosemide (ie, "furosemide stress test") and evaluate the subsequent urine output to help guide decision making regarding the likelihood of AKI progression

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
All-cause Mortality.	90 days following study randomization.

Secondary Outcome Measures

Name	Time	Method
RRT Dependence	90 days following study randomization.
Composite of Death or RRT Dependence.	Measured at day 365.
Measurement of Estimated Glomerular Filtration Rate.	90 days following study randomization.
Measurement of Albuminuria.	90 days following study randomization.
Major Adverse Kidney Outcomes.	90 days following study randomization.	Defined as death, RRT dependence or sustained reduction in kidney function (defined as eGFR \< 75% baseline eGFR).
Mechanical Ventilation-free Days.	Measured from randomization through day 28.
Vasoactive Therapy-free Days	Measured from randomization through day 28.
ICU-free Days	Measured from randomization through day 28.
Hospitalization-free Days	Measured from randomization through day 90.
Death in ICU	Measured in-hospital and at day 28.
EuroQoL EQ-5D-5L.	Measured at day 90 and at day 365.	A measure of health-related quality of life and patient utility.
Health Care Costs.	Measured from baseline through day 365.

Trial Locations

Locations (105)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

University of Florida; 🇺🇸 Gainesville, Florida, United States

University of Kentucy; 🇺🇸 Lexington, Kentucky, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Rhode Island Hospital; 🇺🇸 Providence, Rhode Island, United States

The Miriam Hospital; 🇺🇸 Providence, Rhode Island, United States

Ballarat Hospital; 🇦🇺 Ballarat, Australia

Flinder Medical Centre; 🇦🇺 Bedford Park, Australia

Bendigo Hospital; 🇦🇺 Bendigo, Australia

Eastern Hospital (Box Hill and Maroondah Hospital); 🇦🇺 Box Hill, Australia

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