What is the ICRAKI Trial?
The ICRAKI (Intermittent haemodialysis versus Continuous Renal replacement therapy for severe Acute Kidney Injury) trial is an ongoing non-inferiority, multicentre randomised controlled trial comparing intermittent haemodialysis (IHD) versus continuous renal replacement therapy (CRRT) in 1000 critically ill patients with severe AKI requiring renal replacement therapy 1.
Trial Design and Population
The ICRAKI trial is designed to address the longstanding controversy regarding optimal RRT modality in critically ill patients with AKI. The study specifically enrolls patients who:
- Have acute kidney injury with at least one recognized criterion for initiating RRT
- Are receiving (or have received) invasive mechanical ventilation and/or catecholamine infusion
- Meet criteria for severe AKI requiring dialysis support
This represents a high-acuity population where the choice between continuous and intermittent modalities has remained uncertain despite decades of research 1.
Primary and Secondary Endpoints
The primary endpoint is major adverse kidney events at 90 days (MAKE90), defined as the composite of:
- Death
- RRT dependence
- More than 25% increase in serum creatinine from baseline value
Secondary endpoints include mortality at days 28,60, and 90; RRT dependency rates; ICU and hospital length of stay; time until cessation of RRT; catecholamine-free days; ventilator-free days; RRT-free days through day 28; estimated glomerular filtration rate at hospital discharge; and adverse events 1.
Clinical Context and Rationale
This trial addresses a critical gap in the evidence base. Current guidelines from the Surviving Sepsis Campaign suggest either CRRT or intermittent RRT can be used in patients with sepsis and AKI, with only weak recommendations (moderate quality evidence) 2. The 2002 International Consensus Conference on CRRT identified the comparison between CRRT and intermittent hemodialysis as one of five key areas requiring a multicentered clinical trial 3.
The existing evidence shows no mortality difference between modalities—five prospective RCTs found no significant survival difference, and the most recent large RCT of 360 patients confirmed this finding 2. However, these prior studies had methodological limitations including small sample sizes, heterogeneous populations, randomization failures, and high risk of bias 2.
Current Status
The ICRAKI trial has enrolled more than 300 patients as of the protocol publication 1. The trial is registered at ClinicalTrials.gov (NCT06032884) with registration date September 4,2023.
Clinical Implications
The results of ICRAKI will directly inform clinical decision-making for RRT modality selection in critically ill patients with severe AKI. Currently, CRRT is suggested over intermittent RRT primarily for hemodynamically unstable patients to facilitate fluid balance management (weak recommendation, very low quality evidence) 2. However, this recommendation lacks robust evidence from adequately powered trials.
The trial's focus on patient-centered outcomes (mortality, renal recovery, RRT dependence) rather than surrogate markers makes it particularly relevant for clinical practice. Given that CRRT is more resource-intensive and expensive than intermittent modalities, demonstrating non-inferiority of IHD could have significant implications for resource allocation and patient management strategies 1.
Important caveat: The trial specifically targets critically ill patients requiring mechanical ventilation or vasopressors, so results may not be generalizable to less severely ill patients with AKI requiring RRT 1.