Macdougall IC, et al. - In a multicenter, open-label trial with blinded end-point evaluation, researchers assessed first the noninferiority, and then the safety and effectiveness, of a high-dose regimen of intravenous iron administered proactively, as compared with a low-dose regimen of intravenous iron administered reactively, in patients undergoing hemodialysis. Findings demonstrated that the use of a high-dose regimen of intravenous iron administered proactively brought about a significantly lower dose of erythropoiesis-stimulating agent and a lower incidence of blood transfusion than the use of a low-dose regimen administered reactively.

Methods

• For this investigation, researchers randomly assigned adults undergoing maintenance hemodialysis to receive either high-dose iron sucrose, administered intravenously in a proactive fashion (400 mg monthly, unless the ferritin concentration was >700 μg per liter or the transferrin saturation was ≥40%), or low-dose iron sucrose, administered intravenously in a reactive fashion (0 to 400 mg monthly, with a ferritin concentration of <200 μg per liter or a transferrin saturation of <20% being a trigger for iron administration).
• The composite of nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, or death was the primary end point, evaluated in a time-to-first-event analysis.
• They also analyzed these end points as recurrent events.
• Death, infection rate, and dose of an erythropoiesis-stimulating agent were included other secondary end points.
• If the upper boundary of the 95% confidence interval for the hazard ratio for the primary end point did not cross 1.25, noninferiority of the high-dose group to the low-dose group would be established.

Results

• According to the findings obtained, 2141 patients had randomization (1093 patients to the high-dose group and 1048 to the low-dose group).
• The median follow-up was 2.1 years in this analysis.
• As compared with 145 mg (interquartile range, 100 to 190) in the low-dose group, patients in the high-dose group received a median monthly iron dose of 264 mg (interquartile range [25th to 75th percentile], 200 to 336).
• It was noted that the median monthly dose of an erythropoiesis-stimulating agent was 29,757 IU in the high-dose group and 38,805 IU in the low-dose group (median difference, −7539 IU; 95% confidence interval [CI], −9485 to −5582).
• As compared with 343 (32.7%) in the low-dose group (hazard ratio, 0.88; 95% CI, 0.76 to 1.03; P < 0.001 for noninferiority), 333 patients (30.5%) in the high-dose group had a primary end-point event.
• Four hundred fifty-six events in the high-dose group and 538 in the low-dose group (rate ratio, 0.78; 95% CI, 0.66 to 0.92) were observed in an analysis that used a recurrent-events approach.
• In the two groups, the infection rate was the same.