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The ICRAKI trial was stopped early after interim safety monitoring found higher mortality among critically ill patients initially assigned to intermittent hemodialysis than among those assigned to continuous renal-replacement therapy. The study did not establish why the difference occurred, and early stopping may have made the estimated treatment effect less precise.
A randomized trial of dialysis for critically ill patients with acute kidney injury was stopped early after patients initially assigned to intermittent hemodialysis had higher 90-day mortality than those assigned to continuous renal-replacement therapy. The ICRAKI findings, reported in the New England Journal of Medicine, raise questions about choosing an initial treatment approach for intensive-care patients who need dialysis.
In the trial’s intention-to-treat analysis of 535 patients, the primary outcome — a major adverse kidney event by day 90 — occurred in 78.1% of the intermittent-treatment group and 71.6% of the continuous-treatment group. The study did not show that intermittent hemodialysis was noninferior to continuous therapy for that outcome.
The trial’s data and safety monitoring board halted it early after a higher mortality signal appeared in the intermittent group. By day 90, deaths had occurred in 63.1% of patients assigned to intermittent hemodialysis, compared with 53.5% assigned to continuous therapy. A Kaplan-Meier analysis estimated a higher risk of death in the intermittent group: hazard ratio 1.30, with a 95% confidence interval of 1.04 to 1.63.
The multicenter study enrolled 554 participants across intensive-care units in France, although the reported intention-to-treat analysis included 535. It had originally planned to enroll 1,000 patients. Assigned treatment was maintained for at least four consecutive days unless kidney recovery occurred; after that, clinicians could change modalities. Treatment switching occurred in 21.9% of the intermittent group and 42.5% of the continuous group.
How the Mortality Signal Affects Dialysis Choices
The findings matter because both methods are used to provide renal-replacement therapy to people whose kidneys are failing during critical illness, but they deliver treatment differently. Intermittent hemodialysis clears substances and removes fluid more quickly during treatment sessions, while continuous therapy removes fluid and solutes more gradually over a longer period.
The mortality difference may affect clinical discussions about which method to start, particularly for patients who are unstable. But the study does not establish that intermittent treatment itself caused the deaths, or that one approach is preferable for every patient. The results also do not settle how treatment should be selected after the initial study period, when patients’ conditions and needs may change.
Hypotension was the most common reported complication in both groups, occurring in 68.8% of intermittent-treatment patients and 66.5% of continuous-treatment patients. The similar rates do not by themselves explain the mortality difference; the authors described their additional analyses of hemodynamic stress as exploratory.
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What the Trial Compared
For critically ill patients with acute kidney injury, clinicians have long debated whether intermittent or continuous renal-replacement therapy is the better initial approach. Previous randomized studies, described in an accompanying editorial, were generally small to moderately sized and had largely found no survival difference between the methods.
ICRAKI differed in part because it enrolled patients with documented indications for starting renal-replacement therapy, the researchers said. They noted that earlier trials were conducted before criteria for initiating treatment had been established through trials. That difference in the patients studied may help explain why ICRAKI’s results differ from earlier evidence, but it does not prove the reason for the observed signal.
Participants were seriously ill: most were in intensive care for medical rather than surgical reasons, about half had acute respiratory distress syndrome at baseline, and more than 70% were receiving invasive mechanical ventilation at ICU admission. The median duration of renal-replacement therapy was five days with intermittent treatment and seven days with continuous treatment.
“Unexpected”
— Stéphane Gaudry and colleagues, the ICRAKI researchers
What the Early Stop Leaves Unresolved
The trial does not identify a confirmed cause for the higher mortality in the intermittent group. The researchers said post hoc analyses suggested greater hemodynamic stress with intermittent hemodialysis, but called those findings exploratory and said they do not establish causation.
Stopping early was judged ethically justified by the monitoring board, according to the study authors. They also cautioned that early stopping may have reduced the precision of the treatment estimates and overestimated the size of the mortality effect. The confidence interval and results should therefore be read alongside that limitation, not as proof that the same effect will occur in all settings or patients.
The reported comparison concerns the initial treatment strategy and does not establish which modality is preferable after the first three days. The trial also allowed treatment changes after the initial period, and switching was more frequent in the continuous-therapy group. How those changes affected outcomes is not resolved by the information reported.
How Clinicians May Apply the Findings
The study authors said the results should be considered alongside earlier trials and the limitations created by early termination. The report does not announce a change to clinical guidelines. Existing guidance suggests continuous therapy for patients who are hemodynamically unstable, while the editorial describes variation in how health systems use continuous and intermittent treatment.
Clinicians and researchers will need to assess how the findings apply across different patients and care systems, including strategies that use more than one modality as a patient’s condition changes. The immediate unresolved issue is whether the mortality signal can be explained and reproduced, and how best to weigh the initial treatment choice against later switching. The ICRAKI results alone do not answer those questions.
Key Questions
Why was the ICRAKI trial stopped early?
The trial’s data and safety monitoring board halted it after a higher mortality signal appeared among patients initially assigned to intermittent hemodialysis. The authors said early stopping was justified on ethical grounds, while also warning it may have made the estimated effect less precise.
How many patients died by day 90?
By day 90, deaths had occurred in 63.1% of the intermittent-treatment group and 53.5% of the continuous-treatment group. The study reported a Kaplan-Meier hazard ratio of 1.30 for mortality, with a 95% confidence interval of 1.04 to 1.63.
Does the trial prove intermittent hemodialysis caused more deaths?
No. The trial found an association between initial assignment to intermittent hemodialysis and higher mortality, but the researchers said the cause was not readily explained. Their exploratory analyses did not establish a causal mechanism.
Does ICRAKI show which treatment is best for every patient?
No. The trial compared initial treatment strategies in critically ill patients with acute kidney injury. It does not determine which approach is best for every patient or which modality should be used after the initial treatment period.
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