Ferumoxytol as an intravenous iron replacement therapy in hemodialysis patients.

BACKGROUND AND OBJECTIVES: Intravenous iron is a key component of anemia management for chronic kidney disease (CKD). Ferumoxytol is a unique intravenous iron product that can be administered as a rapid injection in doses up to 510 mg. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a randomized, open-label, controlled, multicenter Phase 3 trial to evaluate the safety and efficacy of intravenous ferumoxytol compared with oral iron. Anemic patients with CKD stage 5D on hemodialysis and on a stable erythropoiesis-stimulating agent regimen received either two injections of 510 mg of ferumoxytol within 7 d (n = 114) or 200 mg elemental oral iron daily for 21 d (n = 116). The primary efficacy endpoint was the change in hemoglobin from baseline to day 35. Safety was closely monitored. RESULTS: Ferumoxytol resulted in a mean increase in hemoglobin of 1.02 +/- 1.13 g/dl at day 35 compared with 0.46 +/- 1.06 g/dl with oral iron (P = 0.0002). Twice as many ferumoxytol-treated patients than oral iron-treated patients achieved a > or =1 g/dl hemoglobin increase at day 35 (P = 0.0002). There was a greater mean increase in transferrin saturation (TSAT) with ferumoxytol compared with oral iron at day 35 (P < 0.0001). The larger hemoglobin increase after ferumoxytol compared with oral iron at day 35 persisted after adjustment for baseline hemoglobin, TSAT, and serum ferritin. Overall adverse event rates were comparable between groups. CONCLUSIONS: In patients on hemodialysis, rapid intravenous injection of 510 mg of ferumoxytol led to significantly greater hemoglobin increases compared with oral iron, with comparable tolerability.

Safety of ferumoxytol in patients with anemia and CKD.

BACKGROUND: Iron deficiency anemia is a common complication in patients with chronic kidney disease (CKD). Currently available intravenous (IV) iron replacement therapies have either inconvenient regimens of administration or adverse event profiles that limit their utility in the outpatient setting. Ferumoxytol is a novel, semisynthetic, carbohydrate-coated, superparamagnetic iron oxide nanoparticle that is administered IV as an injection. The main objective of this study was to assess the safety of ferumoxytol for the treatment of patients with CKD stages 1 to 5 and 5D. STUDY DESIGN: Phase 3, randomized, double-blind, placebo-controlled, crossover, multicenter study of a single 510-mg dose of ferumoxytol versus saline as placebo. SETTING & PARTICIPANTS: 750 patients with CKD stages 1 to 5 and 5D. INTERVENTION: An IV injection of either 17 mL of ferumoxytol or saline placebo over 17 seconds on day 0 and the alternate agent on day 7. OUTCOMES & MEASUREMENTS: Descriptive comparison of adverse events, laboratory tests, and vital signs. RESULTS: Of 750 randomly assigned patients with CKD, 60% were not on dialysis therapy. 713 patients received ferumoxytol, and 711 received placebo. There were 420 adverse events reported; 242 in 152 patients (21.3%) with ferumoxytol and 178 in 119 patients (16.7%) with placebo. The incidence of related adverse events was 5.2% with ferumoxytol and 4.5% with placebo. The most common related adverse events after each treatment included symptoms related to the injection/infusion site, dizziness, pruritus, headache, fatigue, and nausea. Serious adverse events occurred in 21 patients (2.9%) after ferumoxytol and 13 patients (1.8%) after placebo. Serious related adverse events were observed in 1 patient (0.1%) after each treatment. There was no meaningful decrease in blood pressure after administration of ferumoxytol or placebo. LIMITATIONS: Follow-up was 7 days after each study treatment. CONCLUSIONS: Ferumoxytol is well tolerated and has a safety profile similar to placebo in anemic patients with CKD stages 1 to 5 and 5D.

Ferumoxytol for treating iron deficiency anemia in CKD.

Iron deficiency is an important cause of anemia in patients with chronic kidney disease (CKD), but intravenous iron is infrequently used among patients who are not on dialysis. Ferumoxytol is a novel intravenous iron product that can be administered as a rapid injection. This Phase III trial randomly assigned 304 patients with CKD in a 3:1 ratio to two 510-mg doses of intravenous ferumoxytol within 5 +/- 3 d or 200 mg of elemental oral iron daily for 21 d. The increase in hemoglobin at day 35, the primary efficacy end point, was 0.82 +/- 1.24 g/dl with ferumoxytol and 0.16 +/- 1.02 g/dl with oral iron (P < 0.0001). Among patients who were not receiving erythropoiesis-stimulating agents, hemoglobin increased 0.62 +/- 1.02 g/dl with ferumoxytol and 0.13 +/- 0.93 g/dl with oral iron. Among patients who were receiving erythropoiesis-stimulating agents, hemoglobin increased 1.16 +/- 1.49 g/dl with ferumoxytol and 0.19 +/- 1.14 g/dl with oral iron. Treatment-related adverse events occurred in 10.6% of patients who were treated with ferumoxytol and 24.0% of those who were treated with oral iron; none was serious. In summary, a regimen of two doses of 510 mg of intravenous ferumoxytol administered rapidly within 5 +/- 3 d was well tolerated and had the intended therapeutic effect. This regimen may offer a new, efficient option to treat iron deficiency anemia in patients with CKD.

Associations between demographic factors and provider structures on cost and length of stay for hemodialysis patients with vascular access failure.

Vascular access failure (VAF) is a major determinant of morbidity and cost for hemodialysis patients, but little is known about the care patterns and cost implications that are associated with VAF. A total of 952 episodes of VAF in 348 patients were identified using specific procedure codes. Demographic and care pattern characteristics were available as were detailed costs for each episode. The determinants of several important performance measures were evaluated: Cost per episode, inpatient versus outpatient treatment, and length of stay (LOS). Over 5 yr of study, the proportion of VAF episodes that were treated on an outpatient basis increased from 31 to 63%. Average costs of outpatient versus inpatient episodes were $1491 and $8265, respectively. Men were more likely to be treated as outpatients (odds ratio [OR] 1.56; 95% confidence interval [CI] 1.17 to 2.08), but once admitted, their LOS was longer (difference LOS +1.3; 95% CI +0.32 to +2.28) and more costly (delta$ +2603; 95% CI +632 to +4573). Nonblack, nonwhite patients were more likely to be treated as outpatients than were white patients (OR 2.07; 95% CI 1.27 to 3.36) and had shorter LOS once admitted (deltaLOS -2.37; 95% CI -4.23 to -0.49). Compared with Medicare, non-Medicare case-managed insurance was associated with a higher likelihood of outpatient treatment (OR 1.40; 95% CI 1.01 to 1.94) for VAF and shorter LOS (deltaLOS -1.36; 95% CI -2.48 to -0.24) and lower costs (delta$ -2742; 95% CI -5012 to -472) for inpatient treatment. It is concluded that gender and racial factors may influence VAF care. Over time, more VAF episodes are being treated in outpatient settings. Case management may lead to more outpatient treatment and shorter inpatient treatment of VAF.