Intravenous Iron in Patients Undergoing Maintenance Hemodialysis

PIVOTAL Investigators and Committees, 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

Research output: Contribution to journalArticle (Academic Journal)peer-review

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

Fingerprint Dive into the research topics of 'Intravenous Iron in Patients Undergoing Maintenance Hemodialysis'. Together they form a unique fingerprint.

Cite this