Comparison of Iron Dosing Strategies in Patients Undergoing Long-Term Hemodialysis: A Randomized Controlled Trial.

Abstract

BACKGROUND AND OBJECTIVES:

Whether iron supplementation in patients on hemodialysis could be delivered by less frequent but higher single doses compared with the currently more common higher-frequency schedules of lower single iron doses is unknown.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:

We carried out an open-label, randomized, controlled noninferiority trial over 40 weeks in patients on prevalent hemodialysis (n=142). We administered in total 2 g iron as 100 mg iron sucrose biweekly in a continuous (20 × 100 mg) fashion or 500 mg ferric carboxymaltose every 10 weeks in a periodic (4 × 500 mg) fashion. The primary end point was the change in hemoglobin at week 40 from baseline with a noninferiority margin of -0.8 g/dl. Secondary end points were changes in ferritin, transferrin, transferrin saturation, and erythropoiesis-stimulating agent use.

RESULTS:

In total, 108 patients completed the study. At 40 weeks, hemoglobin changed by -0.27 g/dl (95% confidence interval, -0.64 to 0.09) in the iron sucrose arm and by -0.74 g/dl (95% confidence interval, -1.1 to -0.39) in the ferric carboxymaltose arm compared with baseline. Noninferiority was not established in the per-protocol population as hemoglobin changes compared with baseline differed by -0.47 g/dl (95% confidence interval, -0.95 to 0.01) in the ferric carboxymaltose arm compared with the iron sucrose arm. Proportional changes from baseline to week 40 differed by -31% (98.3% confidence interval, -52 to -0.1) for ferritin, by 1% (98.3% confidence interval, -7 to 10) for transferrin, and by -27% (98.3% confidence interval, -39 to -13) for transferrin saturation in the ferric carboxymaltose arm compared with the iron sucrose arm. Erythropoiesis-stimulating agent dosing did not differ between groups. The overall number of adverse events was similar; however, more infections were observed in the iron sucrose arm.

CONCLUSIONS:

An equal cumulative dose of ferric carboxymaltose administered less frequently did not meet noninferiority for maintaining hemoglobin levels compared with iron sucrose administered more frequently.

CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER:

Comparison Study of Two Iron Compounds for Treatment of Anemia in Hemodialysis Patients (COPEFER), NCT02198495.

• Authors: Bernhard Bielesz, Matthias Lorenz, Rossella Monteforte, Thomas Prikoszovich, Michaela Gabriel, Michael Wolzt, Andreas Gleiss, Walter H Hörl, Gere Sunder-Plassmann
• Journal: Clinical journal of the American Society of Nephrology : CJASN (Clin J Am Soc Nephrol) Vol. 16 Issue 10 Pg. 1512-1521 (10 2021) ISSN: 1555-905X [Electronic] United States
• PMID: 34470831 (Publication Type: Comparative Study, Equivalence Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 by the American Society of Nephrology.

Chemical References

• Biomarkers
• Ferric Compounds
• Hematinics
• Hemoglobins
• Transferrin
• ferric carboxymaltose
• Maltose
• Ferritins
• Ferric Oxide, Saccharated

Topics

• Adult
• Aged
• Anemia, Iron-Deficiency (blood, diagnosis, etiology, prevention & control)
• Austria
• Biomarkers (blood)
• Drug Administration Schedule
• Female
• Ferric Compounds (administration & dosage, adverse effects)
• Ferric Oxide, Saccharated (administration & dosage, adverse effects)
• Ferritins (blood)
• Hematinics (administration & dosage, adverse effects)
• Hemoglobins (metabolism)
• Humans
• Infusions, Intravenous
• Male
• Maltose (administration & dosage, adverse effects, analogs & derivatives)
• Middle Aged
• Prospective Studies
• Renal Dialysis (adverse effects)
• Renal Insufficiency, Chronic (blood, diagnosis, therapy)
• Time Factors
• Transferrin (metabolism)
• Treatment Outcome