Comparison of the Anaemia and Transfusion Rates of Pregnant Women Treated with Intravenous versus Oral Iron in the Third Trimester.

OBJECTIVE: To evaluate and compare the blood transfusion requirements during delivery in third-trimester pregnant women with iron deficiency anaemia (IDA) who were treated with intravenous (IV) ferric carboxymaltose (FCM) versus those treated with oral iron supplementation. STUDY DESIGN: Comparative study. Place and Duration of the Study: Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkiye, from January 2017 to December 2022. METHODOLOGY: Pregnant women with haemoglobin (Hb) levels <10 g/dL in their third trimester were included. One group (n = 50) received IV FCM, while the other group (n = 96) received oral iron therapy. Key outcome measures included Hb levels at delivery and the need for a postpartum blood transfusion. Inclusion criteria were third-trimester pregnancy with IDA, and exclusion criteria included haematological or chronic systemic diseases and high-risk pregnancies. RESULTS: The mean initial Hb levels in the third trimester of pregnancy in the FCM group and oral iron group were 8.31 ± 0.96 g/dL and 9.29 ± 1.20 g/dL, respectively (p <0.001). The mean Hb levels in the delivery room were 11.09 ± 1.38 and 9.44 ± 1.16 g/dL, respectively (p <0.001). The rates of postpartum erythrocyte transfusion requirement were 6% (n = 3) and 18.75% (n = 18), respectively (p = 0.037). CONCLUSION: IV FCM administration to pregnant patients with IDA during the third trimester was found to be more effective than oral iron treatment in reducing blood transfusion rates. KEY WORDS: Anaemia, Ferric carboxymaltose, Pregnancy, Iron deficiency, Intravenous iron.

A Cost-Utility Analysis of Ferric Derisomaltose Versus Ferric Carboxymaltose in Patients with Iron Deficiency Anemia in China.

INTRODUCTION: Intravenous (IV) iron is the recommended treatment for patients with iron deficiency anemia (IDA) unresponsive to oral iron treatment, in whom oral iron is contraindicated, or where rapid iron replenishment is required. Ferric derisomaltose (FDI) and ferric carboxymaltose (FCM) are high-dose, rapid-infusion, IV iron formulations that have recently been compared in three head-to-head randomized controlled trials (RCTs), which showed significantly higher incidence of hypophosphatemia after administration of FCM than FDI. The present study objective was to evaluate the cost-utility of FDI versus FCM in a population of patients with IDA in China. METHODS: A previously-published patient-level simulation model was used to model the cost-utility of FDI versus FCM in China. The number of infusions of FDI and FCM was modeled based on the approved posology of the respective formulations using simplified tables of iron need in a population of patients with body weight and hemoglobin levels informed by a Chinese RCT of FCM. Data on the incidence of hypophosphatemia was obtained from the PHOSPHARE-IDA RCT, while data on disease-related quality of life were obtained from SF-36v2 data from the PHOSPHARE-IBD RCT. RESULTS: Over the 5-year time horizon, patients received 3.98 courses of iron treatment on average, requiring 0.90 fewer infusions of FDI than FCM (7.69 vs. 6.79). This resulted in iron procurement and administration cost savings of renminbi (RMB) 206 with FDI (RMB 3,519 vs. RMB 3,312). Reduced incidence of hypophosphatemia-related fatigue resulted in an increase of 0.07 quality-adjusted life years and further cost savings of RMB 782 over 5 years, driven by reduced need for phosphate testing and replenishment. FDI was therefore the dominant intervention. CONCLUSIONS: The results showed that FDI would improve patient quality of life and reduce direct healthcare expenditure versus FCM in patients with IDA in China.

Case Report: High-Dose Ferric Carboxymaltose as an Antianaemic Agent to Avoid Haemotransfusions after Total Hip Replacement.

This article highlights a case of high-dose ferric carboxymaltose (Ferinject®) for the treatment of perioperative iron deficiency anaemia in a 39-year-old patient with dysplastic coxarthrosis. The patient was admitted routinely for a total hip replacement of the left hip joint. She had been suffering from pain, lameness, and restriction of movement in her left hip joint for the past several years. The patient was admitted with initial iron deficiency anaemia of a medium severity (Hgb-96.5 g/L, RBC-3.97 × 1012/L). Laboratory tests were taken to determine the iron deficiency, and transfusion readiness was submitted. The patient received ferric carboxymaltose infusion before surgery. The intraoperative blood loss was-100 mL with an operation duration of 50 min. On the first postoperative day, haemoglobin decreased to 86 g/L. No haemoglobin decrease was observed in the postoperative period, and 92 g/L was the amount of haemoglobin at the time of hospital discharge. The optimal dose for the treatment of perioperative anaemia has not been established; some studies recommend ferric carboxymaltose at a dose of 15 to 20 mg/kg and a maximum of 1000 mg once on the first day after surgery. The uniqueness of this case report is that a high dose of ferric carboxymaltose (1340 mg) during the preoperative period was applied. No side effects such as hypophosphatemia were reported. We believe that, in this clinical case, the patient managed to avoid large intraoperative blood loss and transfusions by using high doses of ferric carboxymaltose.

Response to iron supplementation is similar between boys and girls with pediatric sleep movement disorders.

OBJECTIVES: This study aims to investigate sex differences in response to iron supplementation in children and adolescents suffering from sleep-related movement disorders such as Restless Legs Syndrome (RLS), Periodic Limb Movement Disorder (PLMD), and Restless Sleep Disorder (RSD). METHODS: Data were retrieved and reanalyzed from previous studies involving children with RLS, PLMD, or RSD. The analysis included 54 patients treated with intravenous (IV) ferric carboxymaltose (FCM) and 31 patients treated with oral ferrous sulfate (FS). Demographic, biological, and clinical parameters were compared between sexes. Clinical outcomes were measured using the Clinical Global Impression rating scales for severity (CGI-S) and improvement (CGI-I). RESULTS: In the group treated with IV FCM, no significant differences were found between males and females in demographic (age), biological (ferritin, iron, total iron-binding capacity, transferrin), or clinical parameters (CGI-S and CGI-I). However, among adolescents, females showed significantly better clinical improvement (CGI-I) compared to males (t-value 2.428, p < 0.024). In the group treated with oral FS, no significant sex differences were observed in any parameters. Side effects were reported by a small number of patients, with no significant difference between sexes. CONCLUSION: The findings indicate no major significant sex-based differences in response to iron supplementation for treating sleep-related movement disorders in children and adolescents, despite distinct hormonal and physiological differences in iron metabolism. Both boys and girls benefit similarly from iron treatment during this developmental stage, suggesting that a standardized approach to iron supplementation may be effective. However, individual assessment and monitoring remain crucial to ensure optimal outcomes.

Intravenous ferric carboxymaltose is associated with lowering of plasma phosphate levels in patients with gastric bypass surgery: a retrospective case series.

AIMS: Bariatric surgery induces several micronutrient deficiencies that require supplementation. For iron, parenteral infusions are usually preferred over oral supplementation. Ferric carboxymaltose infusion has been associated with hypophosphataemia, mostly transient and asymptomatic. However, in some cases, ferric carboxymaltose-induced hypophosphataemia may persist for weeks to months and may induce muscle weakness, osteomalacia and bone fractures. The aim of this study was to identify possible predictors of a clinically relevant decrease in serum phosphate after ferric carboxymaltose infusion in patients with previous Roux-en-Y gastric bypass. METHODS: Patients with previous Roux-en-Y gastric bypass who received ferric carboxymaltose infusions between January 2018 and September 2019 and had recorded phosphataemia before and after ferric carboxymaltose infusion at the Lausanne University Hospital, Lausanne, Switzerland, were studied retrospectively. A multiple linear regression model was built with delta phosphataemia as the outcome to investigate the factors related to magnitude of serum phosphate lowering. RESULTS: Seventy-seven patients (70 females and 7 males) with previous Roux-en-Y gastric bypass were studied. Mean age (SD) was 43.2 (10.7) years and median BMI was 30.9 kg/m2 (IQR 27.9-36.4). Sixty-eight patients (88.3%) received an infusion of 500 mg ferric carboxymaltose and 9 patients (11.7%) received 250 mg ferric carboxymaltose. Forty-nine patients (63.6%) developed hypophosphataemia (<0.8 mmol/l) after ferric carboxymaltose infusion. Median plasma phosphate significantly decreased by 0.33 mmol/l (IQR 0.14-0.49) (p<0.0001). Multiple linear regression identified the ferric carboxymaltose dose as the only risk factor significantly associated with the magnitude of serum phosphate lowering, with an additional mean loss of 0.26 mmol/l with a 500 mg infusion compared to a 250 mg infusion (p = 0.020). CONCLUSION: Ferric carboxymaltose infusions substantially decreased plasma phosphate levels in patients with previous Roux-en-Y gastric bypass. Compared to a dose of 250 mg, infusion of a dose of 500 mg ferric carboxymaltose decreased the plasma phosphate further in this population.

Intravenous ferric carboxymaltose versus oral ferrous sulphate for the treatment of moderate to severe postpartum anaemia in Nigerian women (IVON-PP): protocol for an open-label randomised controlled type 1 hybrid effectiveness-implementation trial.

INTRODUCTION: Postpartum anaemia is often caused by iron deficiency with onset during the antepartum period and can be exacerbated by excessive blood loss at birth. Its prevalence is estimated as 50-80% in low-income and middle-income countries. It poses adverse consequences on the mother and negatively impacts her ability to care for her newborn. Prompt treatment of postpartum anaemia is thus important. Adherence to oral iron is reportedly low in Nigeria due to its side effects and forgetfulness by the mothers. Intravenous iron such as ferric carboxymaltose, given as a single dose, might help overcome adherence issues, but investigation in a high-quality randomised control trial in Nigeria is first required while evaluation of challenges around its implementation is also warranted. OBJECTIVE: To determine the clinical effectiveness, tolerability and safety, of using intravenous ferric carboxymaltose (intervention) vs oral ferrous sulphate (control) for treating moderate to severe iron deficiency anaemia in postpartum women and to evaluate implementation of ferric carboxymaltose in treating postpartum anaemia in Nigeria. METHODS AND ANALYSIS: This study is an open-label randomised controlled trial with a concurrent implementation study. It is a hybrid type 1 effectiveness-implementation design conducted in four states across Northern and Southern Nigeria. A total of 1400 eligible and consenting women with postpartum moderate to severe anaemia (haemoglobin concentration <100 g/L) will be randomised to intravenous ferric carboxymaltose; a single dose at 20 mg/kg to a maximum of 1000 mg infusion administered at enrolment (intervention) or oral ferrous sulphate; 200 mg (65 mg elemental iron) two times per day from enrolment until 6 weeks postpartum (control). The primary outcome, proportion of participants who are anaemic (Hb <110 g/L) at 6 weeks postpartum will be analysed by intention-to-treat. Haemoglobin concentration, full blood count, serum iron, serum ferritin, transferrin saturation and total iron binding capacity will be measured at specific intervals. Implementation outcomes such as acceptability and feasibility of using ferric carboxymaltose for postpartum anaemia treatment in Nigeria will be assessed. ETHICS AND DISSEMINATION: This study is approved by the ethics committee of the teaching hospitals, Ministry of Health of the four states as required, National Health Research Ethics Committee and the drug regulatory agency, National Agency for Food and Drug Administration and Control (NAFDAC). Findings of this research will be presented at conferences and will be published in international peer-reviewed journals and shared with stakeholders within and outside Nigeria. TRIAL REGISTRATION NUMBER: International standard randomised controlled trial number: ISRCTN51426226.

Hypophosphatemia attenuates improvements in vitality after intravenous iron treatment in patients with inflammatory bowel disease.

PURPOSE: Iron deficiency anemia is common in people with inflammatory bowel disease (IBD), causing deterioration in quality of life, which can be reversed by treatment that increases iron stores and hemoglobin levels. The present post hoc analyses estimate health state utility values for patients with IBD after treatment with ferric derisomaltose or ferric carboxymaltose and evaluate the health domains driving the changes. METHODS: SF-36v2 responses were recorded at baseline and day 14, 35, 49, and 70 from 97 patients enrolled in the randomized, double-blind, PHOSPHARE-IBD trial (ClinicalTrials.gov ID: NCT03466983), in which patients with IBD across five European countries were randomly allocated to either ferric derisomaltose or ferric carboxymaltose. Changes in SF-36v2 scale scores and SF-6Dv2 health utility values were analyzed by mixed models. RESULTS: In both treatment arms, SF-6Dv2 utility values and all SF-36v2 scale scores, except Bodily Pain, improved significantly (p = < 0.0001). The improvement in SF-6Dv2 utility values showed no significant treatment group difference. The improvement in utility values was completely explained by improvement in Vitality scores. Vitality scores showed significantly larger improvement with ferric derisomaltose versus ferric carboxymaltose (p = 0.026). Patients with the smallest decrease in phosphate had significantly larger improvements in Vitality scores at each time point (p = < 0.05 for all comparisons) and overall (p = 0.0006). CONCLUSIONS: Utility values improved significantly with intravenous iron treatment. Improvement in utility values was primarily driven by Vitality scores, which showed significantly greater improvement in the ferric derisomaltose arm. Smaller decreases in phosphate were associated with significantly higher Vitality scores, suggesting that quality of life improvement is attenuated by hypophosphatemia. The utility values can inform future cost-utility analysis.

Clinical management of iron deficiency anemia in Japan: iron prescription patterns, treatment effectiveness, and assessments.

Iron deficiency anemia is one of the most common types of anemia, but real-world clinical management practices in Japan are unclear. This study retrospectively explored iron prescription patterns, treatment effectiveness, and assessments. Patients with at least one treatment period between September 2020 and September 2022 were included and classified into three groups (ferric carboxymaltose [FCM]: 7437 patients, saccharated ferric oxide [SFO]: 98,648 patients, and oral iron: 359,547 patients). Iron-related laboratory values over time and testing proportions were evaluated. Median baseline hemoglobin levels were lowest with FCM (FCM: 8.10 g/dL, SFO: 8.70 g/dL, oral iron: 9.70 g/dL), but changes in hemoglobin levels by 12 weeks were greatest with FCM (FCM: 3.20 g/dL, SFO: 2.60 g/dL, oral iron: 1.70 g/dL). The median serum ferritin level at 8 weeks after FCM treatment was 43.70 ng/mL for ≤500 mg, versus 123.30 ng/mL for >500 to ≤1500 mg. All groups had a low proportion of serum ferritin and transferrin saturation (TSAT) testing at diagnosis (<38%), which decreased further for post-treatment assessment (<24%). This study suggests the importance of prescribing an appropriate total iron cumulative dose per the package insert, along with diagnosis and assessments based on serum ferritin/TSAT.

Efficacy of ferric carboxymaltose on haemoglobin response among older patients with gastrointestinal bleeding: a randomised clinical trial.

BACKGROUND: Acute gastrointestinal bleeding (AGIB) is common in older patients but the use of iron in this context remains understudied. AIMS: This study aimed to evaluate prospectively the efficacy of ferric carboxymaltose to treat anaemia in older patients after AGIB. METHODS: This randomised double-blinded placebo-controlled clinical trial was conducted in 10 French centres. Eligible patients were 65 years or more, had controlled upper or lower gastrointestinal bleeding and a haemoglobin level of 9-11 g/dl. Patients were randomly assigned, in a 1:1 ratio, to receive either one intravenous iron injection of ferric carboxymaltose or one injection of saline solution. The primary endpoint was the difference in haemoglobin level between day 0 and day 42. Secondary endpoints were treatment-emergent adverse events, serious adverse events, rehospitalisation and improvement of quality of life (QOL) at day 180. RESULTS: From January 2013 to January 2017, 59 patients were included. The median age of patients was 81.9 [75.8, 87.3] years. At day 42, a significant difference in haemoglobin level increase was observed (2.49 g/dl in the ferric carboxymaltose group vs. 1.56 g/dl in the placebo group, P = 0.02). At day 180, QOL, measured on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, improved by 10.5 points in the ferric carboxymaltose group and by 8.2 points in the placebo group (P = 0.56). Rates of adverse events and rehospitalisation were similar in the two groups. CONCLUSIONS: Intravenous iron seems safe and effective to treat anaemia in older patients after AGIB and should be considered as a standard-of-care treatment. ClinicalTrials.gov (NCT01690585).

A meta-analysis of ferric carboxymaltose versus other intravenous iron preparations for the management of iron deficiency anemia during pregnancy.

Objective: We conducted a meta-analysis of randomized clinical trials evaluating the clinical effects of ferric carboxymaltose therapy compared to other intravenous iron in improving hemoglobin and serum ferritin in pregnant women. We also assessed the safety of ferric carboxymaltose vs. other intravenous iron. Data source: EMBASE, PubMed, and Web of Science were searched for trials related to ferric carboxymaltose in pregnant women, published between 2005 and 2021. We also reviewed articles from google scholar. The keywords "ferric carboxymaltose," "FCM," "intravenous," "randomized," "pregnancy," "quality of life," and "neonatal outcomes" were used to search the literature. The search was limited to pregnant women. Selection of studies: Studies related to ferric carboxymaltose in pregnancy were scanned. Observational studies, review articles, and case reports were excluded. Randomized studies in pregnant women involving ferric carboxymaltose and other intravenous iron formulations were shortlisted. Of 256 studies, nine randomized control trials were selected. Data collection: Two reviewers independently extracted data from nine selected trials. Data synthesis: The final effect size for increase in hemoglobin after treatment was significant for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 0.89g/dl [95% confidence interval 0.27,1.51]). The final effect size for the increase in ferritin after treatment was more for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 22.53µg/L [-7.26, 52.33]). No serious adverse events were reported with ferric carboxymaltose or other intravenous iron. Conclusion: Ferric carboxymaltose demonstrated better efficacy than other intravenous iron in increasing hemoglobin and ferritin levels in treating iron deficiency anemia in pregnant women.

Clinical efficacy and safety of intravenous ferric carboxymaltose for treatment of restless legs syndrome: a multicenter, randomized, placebo-controlled clinical trial.

STUDY OBJECTIVES: Iron therapy is associated with improvements in restless legs syndrome (RLS). This multicenter, randomized, double-blind study evaluated the effect of intravenous ferric carboxymaltose (FCM) on RLS. METHODS: A total of 209 adult patients with a baseline International RLS (IRLS) score ≥ 15 were randomized (1:1) to FCM (750 mg/15 mL) or placebo on study days 0 and 5. Ongoing RLS medication was tapered starting on Day 5, with the goal of discontinuing treatment or achieving the lowest effective dose. Co-primary efficacy endpoints were changed from baseline in IRLS total score and the proportion of patients rated as much/very much improved on the Clinical Global Impression (CGI)-investigator (CGI-I) scale at day 42 in the "As-Treated" population. RESULTS: The "As-Treated" population comprised 107 FCM and 101 placebo recipients; 88 (82.2%) and 68 (67.3%), respectively, completed the day 42 assessment. The IRLS score reduction was significantly greater with FCM versus placebo: least-squares mean (95% confidence interval [CI]) -8.0 (-9.5, -6.4) versus -4.8 (-6.4, -3.1); p = .0036. No significant difference was observed in the proportion of FCM (35.5%) and placebo (28.7%) recipients with a CGI-I response (odds ratio 1.37 [95% CI: 0.76, 2.47]; p = .2987). Fewer patients treated with FCM (32.7%) than placebo (59.4%) received RLS interventions between day 5 and study end (p = .0002). FCM was well tolerated. CONCLUSIONS: The IRLS score improved with intravenous FCM versus placebo, although the combination of both co-primary endpoints was not met. Potential methodological problems in the study design are discussed.

Randomized Controlled Trial of Intravenous Ferric Carboxymaltose vs Oral Iron to Treat Iron Deficiency Anemia After Variceal Bleed in Patients With Cirrhosis.

INTRODUCTION: Limited evidence exists on the optimal strategy to correct iron deficiency anemia after variceal bleeding (VB) in cirrhosis. This trial compared the efficacy and safety of intravenous ferric carboxymaltose (IV-FCM) with those of oral iron therapy in this cohort. METHODS: In this open-label, single-center, randomized controlled trial, eligible patients with hemoglobin <10 g/dL and iron deficiency (ferritin <100 ng/mL) after VB received either IV-FCM (1,500-2,000 mg) divided into 2 doses (n = 48) or oral carbonyl iron (100 mg elemental iron/day) (n = 44) for 3 months. The primary outcome was change in hemoglobin at 3 months. Secondary outcomes included improvement in anemia (last hemoglobin >12 g/dL), normalization of iron stores (ferritin >100 ng/mL), liver-related adverse events, adverse drug reactions, and changes in quality of life (CLDQOL questionnaire). RESULTS: Baseline characteristics, including median Child-Turcotte-Pugh score 7 (interquartile range [IQR] 6-9), Model for End-Stage Liver Disease score 12 (IQR 10-17), blood hemoglobin (8.25 ± 1.06 g/dL), and ferritin (30.00 ng/mL [15.00-66.50]), were comparable in both arms. The median increase in hemoglobin at 3 months in the IV and oral arms was 3.65 g/dL (IQR 2.55-5.25) and 1.10 g/dL (IQR 0.05-2.90 g/dL) ( P < 0.001), respectively. Iron stores normalized in 84.6% and 21% of the IV and oral arms, respectively ( P < 0.001). Anemia improved in 50% and 21.9% in the IV and oral arms, respectively ( P < 0.009). Patients in the IV arm showed a significant improvement in all domains of CLDQOL. Liver-related adverse events were comparable in both arms. Transient mild/moderate hypophosphatemia developed in 43% of patients receiving IV-FCM. DISCUSSION: Intravenous iron replacement is efficacious and safe to treat iron deficiency anemia after VB in patients with cirrhosis.

Cellular signaling in the hypoxic cancer microenvironment: Implications for drug resistance and therapeutic targeting.

The rewiring of cellular metabolism is a defining characteristic of cancer, as tumor cells adapt to acquire essential nutrients from a nutrient-poor environment to sustain their viability and biomass. While hypoxia has been identified as a major factor depriving cancer cells of nutrients, recent studies have revealed that cancer cells distant from supporting blood vessels also face nutrient limitations. To overcome this challenge, hypoxic cancer cells, which heavily rely on glucose as an energy source, employ alternative pathways such as glycogen metabolism and reductive carboxylation of glutamine to meet their energy requirements for survival. Our preliminary studies, alongside others in the field, have shown that under glucose-deficient conditions, hypoxic cells can utilize mannose and maltose as alternative energy sources. This review aims to comprehensively examine the hypoxic cancer microenvironment, its association with drug resistance, and potential therapeutic strategies for targeting this unique niche. Furthermore, we will critically evaluate the current literature on hypoxic cancer microenvironments and explore state-of-the-art techniques used to analyze alternate carbohydrates, specifically mannose and maltose, in complex biological fluids. We will also propose the most effective analytical methods for quantifying mannose and maltose in such biological samples. By gaining a deeper understanding of the hypoxic cancer cell microenvironment and its role in drug resistance, novel therapeutic approaches can be developed to exploit this knowledge.

Intravenous iron administration before cardiac surgery reduces red blood cell transfusion in patients without anaemia.

BACKGROUND: Reducing the need for blood transfusion among patients undergoing cardiac surgery FLA reduce postoperative complications and mortality. Our study aimed to assess the effects of administering preoperative i.v. ferric carboxymaltose on postoperative red cell transfusion requirements in patients without anaemia undergoing on-pump cardiac surgery. METHODS: This double-blind, randomised, placebo-controlled trial was conducted between October 2016 and November 2019, with a follow-up period of up to 6 weeks after surgery. Patients without anaemia who underwent on-pump cardiac surgery were included as participants and administered i.v. iron in the form of ferric carboxymaltose or placebo once, 24-72 h before surgery. The primary outcome was the number of red cell units transfused during the first four postoperative days, and the secondary outcome measures were blood haemoglobin concentrations at 4 days and 6 weeks after surgery. RESULTS: The 200 patients included were randomly assigned to the ferric carboxymaltose (n=102) and placebo (n=98) groups. By postoperative Day 4, a significantly lower mean number of red cell units were transfused in the ferric carboxymaltose than in the placebo group, 0.3 (0.8) vs 1.6 (4.4), respectively; P=0.007. The mean haemoglobin concentrations on postoperative Day 4 were 9.7 (1) g dl-1 and 9.3 (1) g dl-1, respectively (P=0.03). Corresponding values at 6 weeks after surgery were 12.6 (1.4) g dl-1 and 11.8 (1.5) g dl-1, respectively (P=0.012). CONCLUSIONS: In patients without anaemia undergoing on-pump cardiac surgery, treatment with a single dose of 1000 mg ferric carboxymaltose i.v. 1-3 days before surgery significantly reduced the need for red cell transfusions and increased the postoperative haemoglobin concentration. CLINICAL TRIAL REGISTRATION: NCT02939794.

Patient reported outcome measures and cardiovascular outcomes following high dose modern intravenous iron in non-dialysis dependent chronic kidney disease: secondary analysis of ExplorIRON-CKD.

Intravenous iron is commonly used to treat iron deficiency anemia in non-dialysis chronic kidney disease (ND-CKD). There is a paucity of information on the potential impact of intravenous iron on patient reported outcome measures, functional status and markers of cardiovascular health. As part of the secondary analysis of this double-blind exploratory randomized controlled trial focusing on patients with iron deficiency (+ /- anemia) and ND-CKD (serum ferritin < 200 µg/L or transferrin saturation ≤ 20% and serum ferritin 200-299 µg/L; CKD stages: 3a-5), 26 patients were randomized in a 1:1 ratio to receive ferric derisomaltose or ferric carboxymaltose. Participants received 1000 mg at baseline and 500-1000 mg at one month to achieve iron repletion. Quality of life and fatigue status were assessed using the Short-Form (36) questionnaire and the fatigue severity scale. Functional status was evaluated using the Duke Activity Status Index and the 1-min-sit-to-stand test. Cardiac markers such as NT-proBNP, Troponin T and pulse wave velocity were monitored. Intravenous iron was associated with similar improvements in most domains of the Short-Form (36) questionnaire, fatigue status, and 1-min-sit-to-stand ability increased significantly by the end of the trial in both groups (p < 0.001). Markers of cardiac function remained stable, with no arterial stiffness impact. Longer term studies are required to further evaluate the impact of intravenous iron on quality of life and cardiac safety in patients with ND-CKD.

In HF with iron deficiency, IV ferric derisomaltose was associated with lower rates of HF hospitalization or CV death.

SOURCE CITATION: Kalra PR, Cleland JG, Petrie MC, et al. Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): an investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial. Lancet. 2022;400:2199-209. 36347265.

Impact of ferric carboxymaltose for iron deficiency at discharge after heart failure hospitalization: a European multinational economic evaluation.

AIMS: Iron deficiency (ID) is comorbid in up to 50% patients with heart failure (HF) and exacerbates disease burden. Ferric carboxymaltose (FCM) reduced HF hospitalizations and improved quality of life when used to treat ID at discharge in patients hospitalized for acute HF with left ventricular ejection fraction <50% in the AFFIRM-AHF trial. We quantified the effect of FCM on burden of disease and the wider pharmacoeconomic implications in France, Germany, Poland, Spain and Sweden. METHODS AND RESULTS: The per country eligible population was calculated, aligning with the 2021 European Society of Cardiology (ESC) HF guidelines and the AFFIRM-AHF trial. Changes in burden of disease with FCM versus standard of care (SoC) were represented by disability-adjusted life years (DALYs), hospitalization episodes and bed days, using AFFIRM-AHF data. A Markov model was adapted to each country to estimate cost-effectiveness and combined with epidemiology data to calculate the impact on healthcare budgets. Between 335 (Sweden) and 13 237 (Germany) DALYs were predicted to be avoided with FCM use annually. Fewer hospitalizations and shorter lengths of stay associated with FCM compared to SoC were projected to result in substantial annual savings in bed days, from 5215 in Sweden to 205 630 in Germany. In all countries, FCM was predicted to be dominant (cost saving with gains in quality-adjusted life years), resulting in net savings to healthcare budgets within 1 year. CONCLUSIONS: This comprehensive evaluation of FCM therapy highlights the potential benefits that could be realized through implementation of the ESC HF guideline recommendations regarding ID treatment.

Ferric Carboxymaltose Versus Ferrous Fumarate in Anemic Children with Inflammatory Bowel Disease: The POPEYE Randomized Controlled Clinical Trial.

OBJECTIVE: To determine whether intravenous (IV) or oral iron suppletion is superior in improving physical fitness in anemic children with inflammatory bowel disease (IBD). STUDY DESIGN: We conducted a clinical trial at 11 centers. Children aged 8-18 with IBD and anemia (defined as hemoglobin [Hb] z-score < -2) were randomly assigned to a single IV dose of ferric carboxymaltose or 12 weeks of oral ferrous fumarate. Primary end point was the change in 6-minute walking distance (6MWD) from baseline, expressed as z-score. Secondary outcome was a change in Hb z-score from baseline. RESULTS: We randomized 64 patients (33 IV iron and 31 oral iron) and followed them for 6 months. One month after the start of iron therapy, the 6MWD z-score of patients in the IV group had increased by 0.71 compared with -0.11 in the oral group (P = .01). At 3- and 6-month follow-ups, no significant differences in 6MWD z-scores were observed. Hb z-scores gradually increased in both groups and the rate of increase was not different between groups at 1, 3, and 6 months after initiation of iron therapy (overall P = .97). CONCLUSION: In this trial involving anemic children with IBD, a single dose of IV ferric carboxymaltose was superior to oral ferrous fumarate with respect to quick improvement of physical fitness. At 3 and 6 months after initiation of therapy, no differences were discovered between oral and IV therapies. The increase of Hb over time was comparable in both treatment groups. TRIAL REGISTRATION: NTR4487 [Netherlands Trial Registry].