Intravenous iron in patients undergoing maintenance hemodialysis

, Iain C. Macdougall, Claire White, Stefan D. Anker, Sunil Bhandari, Kenneth Farrington, Philip A. Kalra, John J. V. McMurray, Heather Murray, Charles R. V. Tomson, David C. Wheeler, Christopher G. Winearls, Ian Ford

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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 320 patients (29.3%) in the high-dose group had a primary end-point event, as compared with 338 (32.3%) in the low-dose group (hazard ratio, 0.85; 95% CI, 0.73 to 1.00; P<0.001 for noninferiority; P=0.04 for superiority). In an analysis that used a recurrent-events approach, there were 429 events in the high-dose group and 507 in the low-dose group (rate ratio, 0.77; 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 superior 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 .).

Original languageEnglish
Pages (from-to)447-458
Number of pages12
JournalNew England Journal of Medicine
Volume380
Issue number5
DOIs
Publication statusPublished - 31 Jan 2019

Keywords

  • Administration, Intravenous
  • Adult
  • Aged
  • Anemia/drug therapy
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Ferric Oxide, Saccharated/administration & dosage
  • Ferritins/blood
  • Follow-Up Studies
  • Hematinics/administration & dosage
  • Humans
  • Kidney Failure, Chronic/therapy
  • Male
  • Middle Aged
  • Prospective Studies
  • Renal Dialysis/adverse effects
  • Single-Blind Method
  • Transferrin/analysis

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    , 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., & Ford, I. (2019). Intravenous iron in patients undergoing maintenance hemodialysis. New England Journal of Medicine, 380(5), 447-458. https://doi.org/10.1056/NEJMoa1810742