An oral iron formulation may be a safe and effective treatment for anaemia in patients with chronic kidney disease, Stanford researchers found, pointing to an alternative to intravenous iron, the only treatment approved by the US Food and Drug Administration.
Nearly 30m adults in the US are living with chronic kidney disease, and iron deficiency exists in more than half of these patients. Unfortunately, most affected patients are not receiving treatment to address their dangerously low levels of iron, which can lead to low red blood cell counts, or anemia. In addition, the only treatments approved by the US Food and Drug Administration for iron deficiency are intravenous formulations of iron, which carry certain risks including anaphylaxis.
Dr Glenn Chertow (Stanford University School of Medicine) and his colleagues conducted a study to test whether an oral iron formulation called ferric citrate might be a safe and effective alternative. In the phase 3 randomized double-blind clinical trial, 117 patients received oral ferric citrate and 115 received placebo. The primary end point was the proportion of patients who achieved a ≥1.0-g/dl increase in hemoglobin (a reflection of red blood cell counts) at any time during a 16-week randomised period.
During the trial, 52.1% of patients receiving ferric citrate achieved the primary end point compared with 19.1% of patients receiving placebo. A treatment effect was seen as early as 1-2 weeks after the start of treatment, and the response was durable. Rates of serious adverse events were similar in the ferric citrate (12.0%) and placebo groups (11.2%). Gastrointestinal disorders such as diarrhoea and constipation were the most common adverse events, and they tended to be mild or moderate.
"Secondary endpoints related to correction of anemia and lowering of serum phosphate were also reached in ferric citrate-treated patients. In addition, exploratory endpoints showed improvements in other parameters of mineral metabolism in ferric citrate-treated patients," said Chertow. In addition to affecting iron levels, ferric citrate also functions as an intestinal phosphate binder and has been approved for the treatment of hyperphosphatemia in patients on dialysis.
Chertow noted that although oral ferric citrate boosted hemoglobin levels in the study, additional research is needed to see if the drug prolongs life or improves patients' quality of life.
Abstract
Iron deficiency anemia is common and consequential in nondialysis-dependent CKD (NDD-CKD). Efficacy and tolerability of conventional oral iron supplements are mixed; intravenous iron administration associates with finite but important risks. We conducted a randomized double-blind clinical trial in adults with NDD-CKD and iron deficiency anemia to compare the safety and efficacy of oral ferric citrate (n=117) and placebo (n=115). The primary end point was the proportion of patients who achieved a ≥1.0 g/dl increase in hemoglobin at any time during a 16-week randomized period. Patients who completed the 16-week period could also participate in an 8-week open-label extension period. Significantly more patients randomized to ferric citrate achieved the primary end point (61 [52.1%] versus 22 [19.1%] with placebo; P<0.001). All secondary end points reached statistical significance in the ferric citrate group, including the mean relative change in hemoglobin (0.84 g/dl; 95% confidence interval, 0.58 to 1.10 g/dl; P<0.001) and the proportion of patients who achieved a sustained increase in hemoglobin (≥0.75 g/dl over any 4-week period during the randomized trial; 57 [48.7%] versus 17 [14.8%] with placebo; P<0.001). Rates of serious adverse events were similar in the ferric citrate (12.0%) and placebo groups (11.2%). Gastrointestinal disorders were the most common adverse events, with diarrhea reported in 24 (20.5%) and 19 (16.4%) and constipation in 22 (18.8%) and 15 (12.9%) patients treated with ferric citrate and placebo, respectively. Overall, in patients with NDD-CKD, we found oral ferric citrate to be a safe and efficacious treatment for iron deficiency anemia.
Authors
Steven Fishbane, Geoffrey A Block, Lisa Loram, John Neylan, Pablo E Pergola, Katrin Uhlig, Glenn M Chertow
[link url="https://www.sciencedaily.com/releases/2017/01/170112180936.htm"]American Society of Nephrology material[/link]
[link url="http://jasn.asnjournals.org/content/early/2017/01/11/ASN.2016101053"]Journal of the American Society of Nephrology abstract[/link]