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

Unity Health Toronto3,019 enrolled

Overview

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

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

3,019

Conditions

Acute Kidney Injury

Interventions

Standard RRT initiationOTHER

In the absence of kidney function recovery, the initiation of RRT will be permitted if one of the following develops: serum potassium ≥ 6.0 mmol/L; pH ≤ 7.20 or serum bicarbonate ≤ 12 mmol/L; evidence of severe respiratory failure, based on a PaO2/FiO2 ≤ 200 and clinical perception of volume overload; and/or persistent AKI \> 72 hours following the time of randomization.

Accelerated RRT initiationOTHER

A dialysis catheter will be placed and RRT initiated as soon as possible and within 12 hours of eligibility. This 12 hour window includes the time needed to obtain consent.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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