STandard versus Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury: Study Protocol for a Multi-National, Multi-Center, Randomized Controlled Trial

BACKGROUND: The optimal timing of renal replacement therapy (RRT) initiation in critically ill patients with acute kidney injury (AKI) remains controversial. OBJECTIVE: In critically ill patients with AKI, to determine whether the accelerated initiation of RRT reduces mortality compared to a strategy of standard RRT initiation whereby RRT is initiated if urgent complications of AKI arise or based on clinician judgment. DESIGN: Pragmatic allocation-concealed open-label randomized controlled trial. SETTING: Up to 170 centers in Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, Ireland, Italy, Finland, New Zealand, Switzerland, the United Kingdom, and the United States. PATIENTS: We will enroll at least 2,866 critically ill patients with AKI stages 2 or 3 (defined as doubling of serum creatinine from baseline or serum creatinine ≥354 µmol/L with increase of ≥27 µmol/L from baseline or urine output <6 mL/kg in preceding 12 hours). Patients will be excluded if 1 or more of the following is/are present: potassium >5.5 mmol/L; bicarbonate <15 mmol/L; concomitant intoxication necessitating RRT; philosophy of care precluding escalation to RRT; any RRT in preceding 2 months; kidney transplant within the past year; preexisting estimated glomerular filtration rate <20 mL/min/1.73 m(2); AKI etiology attributable to obstruction, glomerulonephritis, vasculitis, microangiopathy, or acute interstitial nephritis; clinician opinion that urgent RRT is mandated; or clinician opinion that RRT must be deferred. METHODS: Participants will be randomized to one of two strategies: accelerated RRT initiation, which entails the initiation of RRT within 12 hours of the patient fulfilling all eligibility criteria, or standard RRT initiation, whereby clinicians would be discouraged from initiating RRT unless a conventional trigger for RRT initiation arises or if AKI persists for ≥72 hours. MEASUREMENTS: The primary outcome is all-cause mortality at 90 days following randomization. Key secondary outcomes include RRT dependence, residual kidney function, health services use, and health-related quality of life, all assessed at 90 days after randomization. In jurisdictions where it is feasible, participants will be followed through day 365 using linked administrative data. RESULTS: Through March 18, 2019, we have recruited 2623 (92% of target) participants. LIMITATIONS: Reliance on physician declaration of equipoise may create heterogeneity across the trial population; open-label design may introduce bias and uneven postrandomization cointerventions; variations in practice (eg, choice of RRT modality and RRT prescription) likely exist across sites. CONCLUSIONS: Once complete, the STARRT-AKI trial will provide the most robust evidence to date to guide clinical practice on the optimal timing of RRT initiation among critically ill patients with AKI. TRIAL REGISTRATION: Clinicaltrials.gov NCT02568722.