Standard versus accelerated initiation of renal replacement therapy in acute kidney injury (STARRT-AKI): study protocol for a randomized controlled trial

Abstract

BackgroundAcute kidney injury is a common and devastating complication of critical illness, for which renal replacement therapy is frequently needed to manage severe cases. While a recent systematic review suggested that “earlier” initiation of renal replacement therapy improves survival, completed trials are limited due to small size, single-centre status, and use of variable definitions to define “early” renal replacement therapy initiation.Methods/designThis is an open-label pilot randomized controlled trial. One hundred critically ill patients with severe acute kidney injury will be randomly allocated 1:1 to receive “accelerated” initiation of renal replacement therapy or “standard” initiation at 12 centers across Canada. In the accelerated arm, participants will have a venous catheter placed and renal replacement therapy will be initiated within 12 hours of fulfilling eligibility. In the standard initiation arm, participants will be monitored over 7 days to identify indications for renal replacement therapy. For participants in the standard arm with persistent acute kidney injury, defined as a serum creatinine not declining >50% from the value at the time of eligibility, the initiation of RRT will be discouraged unless one or more of the following criteria are fulfilled: serum potassium ≥6.0 mmol/L; serum bicarbonate ≤10 mmol/L; severe respiratory failure (PaO2/FiO2<200) or persisting acute kidney injury for ≥72 hours after fulfilling eligibility. The inclusion criteria are designed to identify a population of critically ill adults with severe acute kidney injury who are likely to need renal replacement therapy during their hospitalization, but not immediately. The primary outcome is protocol adherence (>90%). Secondary outcomes include measures of feasibility (proportion of eligible patients enrolled in the trial, proportion of enrolled patients followed to 90 days for assessment of vital status and the need for renal replacement therapy) and safety (occurrence of adverse events).DiscussionThe optimal timing of renal replacement therapy initiation in patients with severe acute kidney injury remains uncertain, representing an important knowledge gap and a priority for high-quality research. This pilot trial is necessary to establish protocol feasibility, confirm the safety of participants and obtain estimated events rates for design of a large definitive trial.Trial registration numberNCT01557361

Timing of RRT Based on the Presence of Conventional Indications

“…Our study provides valuable data for planning an RCT. Most importantly, one half of the patients treated with RRT presented with conventional indications at ICU admission, and many of them would, therefore, not be eligible for randomization in an RCT that is in development (34). Defining appropriate laboratory inclusion criteria for an RCT might be challenging, because the ability of novel biomarkers to predict the receipt of RRT in patients with AKI is poor.…”

Timing of Renal Replacement Therapy

“…In Canada, the STARRT-AKI trial, a multi-centre pilot RCT has recently been completed [ 47 ].This trial enrolled critically ill patients with severe AKI to a strategy of early RRT (within 12 h of eligibility) or standard initiation of RRT (based on persistent AKI and/or development of more classic indications).The ongoing IDEAL-ICU trial is a multicentre RCT in France with a target enrolment of 824 patients that seeks to randomize critically ill patients with septic shock and severe AKI (defi ned as a three-fold rise in serum creatinine and urine output <0.3 mL/kg/h for 12 h) [ 48 ]. The early strategy calls for starting RRT within 12 h of fulfi lling AKI criteria whereas in the late arm RRT commences 48-60 h thereafter.…”

Have biomarkers failed in acute kidney injury? No

“…Biomarkers have also been shown to be informative for the inclusion of patients with AKI in intervention trials [10,14,15]. The PrevAKI trial is the most recent example of trials utilizing biomarkers to trigger patient randomization and we anticipate growth of this technique given these successes [10].…”