Intravenous iron in patients undergoing maintenance hemodialysis

Macdougall, I. C. et al. (2019) Intravenous iron in patients undergoing maintenance hemodialysis. New England Journal of Medicine, 380(5), pp. 447-458. (doi: 10.1056/NEJMoa1810742) (PMID:30365356)

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Abstract

Background: Intravenous iron is a standard treatment for patients undergoing hemodialysis, but comparative data regarding clinically effective regimens are limited. Methods: In a multicenter, open-label trial with blinded end-point evaluation, we 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 primary end point was the composite of nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, or death, assessed in a time-to-first-event analysis. These end points were also analyzed as recurrent events. Other secondary end points included death, infection rate, and dose of an erythropoiesis-stimulating agent. Noninferiority of the high-dose group to the low-dose group would be established if the upper boundary of the 95% confidence interval for the hazard ratio for the primary end point did not cross 1.25. Results: A total of 2141 patients underwent randomization (1093 patients to the high-dose group and 1048 to the low-dose group). The median follow-up was 2.1 years. Patients in the high-dose group received a median monthly iron dose of 264 mg (interquartile range [25th to 75th percentile], 200 to 336), as compared with 145 mg (interquartile range, 100 to 190) in the low-dose group. 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). A total of 333 patients (30.5%) in the high-dose group had a primary end-point event, 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). In an analysis that used a recurrent-events approach, there were 456 events in the high-dose group and 538 in the low-dose group (rate ratio, 0.78; 95% CI, 0.66 to 0.92). The infection rate was the same in the two groups. Conclusions: Among patients undergoing hemodialysis, a high-dose intravenous iron regimen administered proactively was noninferior to a low-dose regimen administered reactively and resulted in lower doses of erythropoiesis-stimulating agent being administered. (Funded by Kidney Research UK; PIVOTAL EudraCT number, 2013-002267-25.)

Item Type:Articles
Additional Information:Funded by Kidney Research UK; PIVOTAL EudraCT number, 2013-002267-25. A correction to this article is available at https://doi.org/10.1056/NEJMx180044.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Murray, Mrs Heather and Ford, Professor Ian and McMurray, Professor John
Authors: Macdougall, I. C., White, C., Anker, S. D., Bhandari, S., Farrington, K., Kalra, P. A., McMurray, J. J.V., Murray, H., Tomson, C. R.V., Wheeler, D. C., Winearls, C. G., and Ford, I.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:New England Journal of Medicine
Publisher:Massachusetts Medical Society
ISSN:0028-4793
ISSN (Online):1533-4406
Published Online:26 October 2018
Copyright Holders:Copyright © 2018 Massachusetts Medical Society
First Published:First published in New England Journal of Medicine 380(5): 447-458
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher
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