Bernhard Bielesz1, Matthias Lorenz2, Rossella Monteforte3, Thomas Prikoszovich2, Michaela Gabriel2, Michael Wolzt4, Andreas Gleiss5, Walter H Hörl3, Gere Sunder-Plassmann3. 1. Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria bernhard.bielesz@meduniwien.ac.at. 2. Vienna Dialysis Center, Vienna, Austria. 3. Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria. 4. Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria. 5. Center for Medical Statistics, Informatics, and Intelligent Systems, Institute of Clinical Biometrics, Medical University of Vienna, Vienna, Austria.
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.
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: Iain C Macdougall; William E Strauss; Justin McLaughlin; Zhu Li; Frank Dellanna; Joachim Hertel Journal: Clin J Am Soc Nephrol Date: 2014-01-23 Impact factor: 8.237
Authors: Iain C Macdougall; Sunil Bhandari; Claire White; Stefan D Anker; Kenneth Farrington; Philip A Kalra; Patrick B Mark; John J V McMurray; Chante Reid; Michele Robertson; Charles R V Tomson; David C Wheeler; Christopher G Winearls; Ian Ford Journal: J Am Soc Nephrol Date: 2020-04-06 Impact factor: 10.121
Authors: Soheir Beshara; Jens Sörensen; Mark Lubberink; Vladimir Tolmachev; Bengt Långström; Gunnar Antoni; Bo G Danielson; Hans Lundqvist Journal: Br J Haematol Date: 2003-03 Impact factor: 6.998
Authors: Chaim Charytan; Marializa V Bernardo; Todd A Koch; Angelia Butcher; David Morris; David B Bregman Journal: Nephrol Dial Transplant Date: 2012-12-05 Impact factor: 5.992
Authors: Sunil Bhandari; Philip A Kalra; Mario Berkowitz; Diogo Belo; Lars L Thomsen; Myles Wolf Journal: Nephrol Dial Transplant Date: 2021-01-01 Impact factor: 5.992