Evaluation of a Single Dose of Ferric Carboxymaltose in Fatigued, Iron-Deficient Women – PREFER a Randomized, Placebo-Controlled Study

Abstract

BackgroundUnexplained fatigue is often left untreated or treated with antidepressants. This randomized, placebo-controlled, single-blinded study evaluated the efficacy and tolerability of single-dose intravenous ferric carboxymaltose (FCM) in iron-deficient, premenopausal women with symptomatic, unexplained fatigue.MethodsFatigued women (Piper Fatigue Scale [PFS] score ≥5) with iron deficiency (ferritin <50 µg/L and transferrin saturation <20%, or ferritin <15 µg/L) and normal or borderline hemoglobin (≥115 g/L) were enrolled in 21 sites in Austria, Germany, Sweden and Switzerland, blinded to the study drug and randomized (computer-generated randomization sequence) to a single FCM (1000 mg iron) or saline (placebo) infusion. Primary endpoint was the proportion of patients with reduced fatigue (≥1 point decrease in PFS score from baseline to Day 56).ResultsThe full analysis included 290 women (FCM 144, placebo 146). Fatigue was reduced in 65.3% (FCM) and 52.7% (placebo) of patients (OR 1.68, 95%CI 1.05–2.70; p = 0.03). A 50% reduction of PFS score was achieved in 33.3% FCM- vs. 16.4% placebo-treated patients (p<0.001). At Day 56, all FCM-treated patients had hemoglobin levels ≥120 g/L (vs. 87% at baseline); with placebo, the proportion decreased from 86% to 81%. Mental quality-of-life (SF-12) and the cognitive function scores improved better with FCM. ‘Power of attention’ improved better in FCM-treated patients with ferritin <15 µg/L. Treatment-emergent adverse events (placebo 114, FCM 209; most frequently headache, nasopharyngitis, pyrexia and nausea) were mainly mild or moderate.ConclusionA single infusion of FCM improved fatigue, mental quality-of-life, cognitive function and erythropoiesis in iron-deficient women with normal or borderline hemoglobin. Although more side effects were reported compared to placebo, FCM can be an effective alternative in patients who cannot tolerate or use oral iron, the common treatment of iron deficiency. Overall, the results support the hypothesis that iron deficiency can affect women’s health, and a normal iron status should be maintained independent of hemoglobin levels.Trial Registration ClinicalTrials.gov NCT01110356

Ferric carboxymaltose vs. oral iron in the treatment of pregnant women with iron deficiency anemia: an international, open-label, randomized controlled trial (FER-ASAP)

“…It should be noted that study participants were not blinded to treatment and, therefore, the assessment of quality-of-life could have been influenced by subject bias. However, our findings are in accordance with those from a previous randomized, controlled trial in which FCM was found to significantly improve symptomatic fatigue in iron-deficient women [21]. Increased vitality can be of particular benefit in coping with the extreme physical stresses experienced by women during pregnancy and childbirth.…”

“…Pregnant women aged ≥ 18 years, in their second or third trimester (gestational weeks [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] and with serum ferritin levels ≤ 20 ng/mL and IDA [defined as hemoglobin (Hb) 8.0-10.4 g/dL for gestation weeks [16][17][18][19][20][21][22][23][24][25][26] or Hb ≤ 11.0 g/dL for gestation weeks 27-33] were eligible for this study. Women were excluded if they had a significant bleed or surgery within 3 months prior to screening, received a blood transfusion, erythropoietin treatment, oral iron (unless the dose was ≤ 100 mg iron per day) or parenteral iron treatment during the month prior to screening, or were anticipated to need a blood transfusion during the study period.…”

How we diagnose and treat iron deficiency anemia

“…FCM, the most recently approved formulation, has been safely administered as a 1,000-mg infusion over 15 min [66], and is approved in Europe at this dose. In the US, its current approval is for not more than 750 mg administered over the same interval.…”

Hypersensitivity reactions to intravenous ferric carboxymaltose in a patient with iron deficiency anemia: a rare case report

“…7 The adverse effects like rashes (in form of allergy), vomiting, breathlessness and myalgia were also seen in the population who were involved in the clinical trial phases but these adverse reaction were rare (<1%), which is also known as type 1 Hypersensitivity reactions. 3,8 A fast iron infusion rate is a well-recognized risk factor, one possible explanation being the rapid increase in labile free iron.…”