Dose Of Ferric Carboxymaltose Research Articles

Ferric carboxymaltose in reducing blood transfusions and infections after cardiac surgery

ObjectiveIron supplementation may reduce postoperative anemia, blood transfusions, and infections in patients undergoing surgery. We sought to assess efficacy and safety of prophylactic intravenous iron supplementation in patients without anemia undergoing cardiac surgery. MethodsIn this investigator-initiated industry-sponsored single-center randomized double-blind parallel group trial, we enrolled patients undergoing coronary bypass, aortic or mitral valve or ascending aortic surgery who fulfilled prespecified iron blood test safety criteria. Patients were randomized to receive either a single intravenous 1000 mg dose of ferric carboxymaltose (FCM) or placebo (saline only). Independent unblinded study nurse administered the infusion with masked lines and cannula 2 to 21 days before surgery. Primary efficacy end point was a composite of in-hospital blood transfusions >2 U and nosocomial infection. The trial was registered in Eudract (2017-004901-41). ResultsAltogether 171 patients were screened and 78 randomly assigned to FCM (n = 39) or placebo (n = 39). Trial was prematurely discontinued for futility with regard to reaching the primary end point by the recommendation of the independent data monitoring committee. The primary end point occurred in 3 (7.7%) versus 3 (7.7%) (P = 1.00) of patients assigned to FCM and placebo, respectively, with no difference in blood transfusions >2 U. Fewer hospital readmissions by 3 months follow-up (1 [2.6%] vs 8 [20.5%]; P = .028) were noted in FCM group in a post hoc analysis. Ferritin levels were higher in the FCM group at 3 months indicating more preserved iron stores. ConclusionsProphylactic treatment with FCM was safe but did not reduce the need for blood transfusions or postoperative infections at index hospitalization in patients without anemia undergoing cardiac surgery.

Implementation fidelity of intravenous ferric carboxymaltose administration for iron deficiency anaemia in pregnancy: a mixed-methods study nested in a clinical trial in Nigeria

BackgroundIron deficiency anaemia is common among pregnant women in Nigeria. The standard treatment is oral iron therapy, which can be sub-optimal due to side effects. Intravenous ferric carboxymaltose (FCM) is an evidenced-based alternative treatment with a more favourable side effect profile requiring administration according to a standardized protocol. In this study, we assessed the fidelity of administering a single dose of FCM according to protocol and identified factors influencing implementation fidelity.MethodsWe used a mixed-method approach with a sequential explanatory design nested in a clinical trial across 11 facilities in Lagos and Kano States, Nigeria. Guided by a conceptual framework of implementation fidelity, we quantitatively assessed adherence to protocol by directly observing every alternate FCM administration, using an intervention procedure checklist, and compared median adherence by facility and state. Qualitative fidelity assessment was conducted via in-depth interviews with 14 skilled health personnel (SHP) from nine purposively selected health facilities, using a semi-structured interview guide. We analyzed quantitative data using descriptive and inferential statistics in Stata and used thematic analysis to analyze the transcribed interviews in NVivo.ResultsA total of 254 FCM administrations were observed across the 11 study sites, with the majority in secondary (63%), followed by primary healthcare facilities (PHCs) (30%). Overall, adherence to FCM administration as per protocol was moderate (63%) and varied depending on facility level. The lowest level of adherence was observed in PHCs (36%). Median, adherence level showed significant differences by facility level (p = 0.001) but not by state (p = 0.889). Teamwork and availability of protocols are facilitation strategies that contributed to high fidelity. However, institutional/ logistical barriers are contextual factors that influenced the varied fidelity levels observed in some facilities.ConclusionsCollaborative teams and access to operating protocols resulted in high fidelity in some facilities. However, in some PHCs, fidelity to FCM was low due to contextual factors and intervention complexities, thereby influencing the quality of delivery. In Nigeria, scale-up of FCM will require attention to staff strength, teamwork and availability of administration protocols, in order to optimize its impact on anaemia in pregnancy.

Trends of phosphorus levels after intravenous administration of ferric carboxymaltose

Abstract Background Iron deficiency and anaemia are present in a large number of patients with heart failure. Intravenously ferric carboxymaltose (FCM) is the recommended treatment, but it may be associated with hypersensitivity reaction and hypophosphatemia, the later mainly in subjects with normal renal function. The prevalence of hypophosphatemia driven by FCM in patients with heart failure (HF) is not well established. Purpose To assess the prevalence and trends of serum phosphorus levels after FCM administration in outpatients with HF. Methods Prospective, observational, consecutive, and descriptive study of patients admitted in a HF clinic eligible to receive FCM between January 2022 and June 2022. Phosphorus and calcium homeostasis regulators (magnesium, vitamin D, parathyroid hormone, alkaline phosphatase) were drawn at baseline and after 3 weeks of the infusion. In those patients with documented hypophosphatemia after iron administration, a third measurement was performed at three months from baseline. Paired T-test was used to compare mean values and logistic regression to predict relationship of changes in serum phosphorus with other factors. Results 101 patients were included (71.5 ± 10.6 years, 31.7% women, LVEF 43.9 ±11.9%, 49.5% of ischaemic aetiology, glomerular filtration rate 39.44 ±10 mL/min/m2). Mean baseline phosphorous was 3.64 ± 0.66 mg/dL, declining to 2.74 ±0.88 mg/dL (p for trend = 0.001). Calcium, magnesium, and vitamin D also showed a post-infusion declining tendency (p = 0.001, p = 0.05 and p= 0.002, respectively), whereas PTH significantly increased (p = 0.015). At three weeks, 38 (37.6%) patients had phosphorous levels below the normal threshold (mean 2.15 ± 0.76 mg/dl), which normalized at three months from baseline (mean 3.12 ±0.77 mg/dl; p = 0.71) without specific treatment. Figure 1 shows phosphorus dynamics of the 38 patients with infusion hypophosphatemia. There was no predicted correlation between FCM dose, glomerular filtration rate and phosphorous trends (p = 0.627, P = 0.234 respectively). No clinical adverse event was reported. Conclusion Ferric carboxymaltose infusion in patients with HF is associated with a decline in circulating phosphorous, with 1 in 3 patients showing frank hypophosphatemia. This effect is transient and does not require treatment nor active phosphorus monitoring.Trends of hypophosphatemia

Ferric Carboxymaltose in Patients with Acute Decompensated Heart Failure and Iron Deficiency: A Real-Life Study.

Background: The correction of iron deficiency (ID) with ferric carboxymaltose (FCM) is a recommended intervention in heart failure (HF) with reduced ejection fraction. Our aim is to evaluate, in a real-life setting, the clinical significance of ID screening and FCM treatment in acute decompensated HF (ADHF). Methods: In a cohort of ADHF patients, the prevalence of ID and FCM administration were investigated. Among the 104 patients admitted for ADHF, in n = 90 (median age 84, 53.5% with preserved left ventricular ejection fraction-LVEF), a complete iron status evaluation was obtained. ID was detected in n = 73 (81.1%), 55 of whom were treated with in-hospital FCM. The target dose was reached in n = 13. Results: No significant differences were detected in terms of age, sex, comorbidities, or LVEF between the FCM-supplemented and -unsupplemented patients. During a median follow-up of 427 days (IQR 405-466) among the FCM-supplemented patients, only 14.5% received FCM after discharge; the mortality and rehospitalizations among FCM-supplemented and -unsupplemented patients were similar (p = ns). In a follow-up evaluation, ID was still present in 75.0% of the FCM-supplemented patients and in 69.2% of the unsupplemented patients (p = ns). Conclusions: In this real-life ADHF cohort, FCM was administered at lower-than-prescribed doses, thus having no impact on ID correction. The significance of our findings is that only achieving the target dose of FCM and pursuing outpatient treatment can correct ID and produce long-term clinical benefits.

Patient-Reported Outcomes After Ferric Carboxymaltose Treatment for Iron Deficiency Anemia: A Prospective Observational Study.

Iron deficiency anemia (IDA) is a common cause of fatigue and impaired quality of life. The present study aimed to evaluate the impact of intravenous iron supplementation with ferric carboxymaltose (FCM) on fatigue, physical function, and general health among patients with IDA attending routine clinical care. This was a prospective, single arm, observational study of adult patients prescribed with intravenous FCM for the treatment of IDA during routine clinical care. We used Patient-Reported Outcomes Measurement Information System (PROMIS) instruments to evaluate fatigue (PROMIS Short Form v1.0 13a [FACIT-Fatigue]), general health status (PROMIS Scale v1.2), and physical function (PROMIS Short Form v2.0 4a) before and at 3 and 6 months after FCM treatment. A total of 152 patients were enrolled. Mean age was 47.4 ± 16.0 years and 82.2% were female. Mean serum hemoglobin was 10.2 ± 1.4 g/dL at baseline. All patients were treated with at least one FCM dose at baseline, with 77.6% receiving a two-dose treatment course. The mean baseline FACIT-Fatigue score was 61.0 ± 9.0, improving significantly to 50.2 ± 9.5 at 3 months after FCM treatment. A minimum 5-point improvement, pre-defined as clinically meaningful, was seen in the FACIT-Fatigue, PROMIS Global Physical Health, Global Mental Health and PROMIS Physical Function scores for 72.7%, 52.8%, 41.7% and 39.8% of patients at 3 months (p < 0.0001 for each change from baseline), with statistically significant improvement continuing at 6 months. Mean serum hemoglobin was significantly increased at both 3 and 6 months (12.8 g/dL [N = 44] and 12.4 g/dL [N = 54], respectively). IDA patients attending routine clinical practice reported substantial levels of fatigue and impairments in physical function and global health prior to intravenous iron treatment. Patients experienced significant improvements in fatigue symptoms, physical function, and global health at 3 months after treatment with FCM, which were sustained at 6 months.

Ferric carboxymaltose for patients with heart failure in all-range ejection fraction

Introduction and objectivesIron deficiency (ID) is common in heart failure (HF) patients and is linked to exercise impairment, worse quality of life, and HF hospitalisation. Clinical practice guidelines recommend checking and correcting ID with ferric carboxymaltose (FCM). However, there is a lack of evidence in patients with left ventricular ejection fraction (LVEF) >40%. MethodsWe included all HF outpatients treated with FCM after ID diagnosis (ferritin <100ng/mL or ferritin 100–299ng/mL and transferrin saturation <20%). We analysed clinical and analytical parameters before FCM administration and at 3 months according to LVEF: preserved (>50%), mildly reduced (41–49%), and reduced (<40%). ResultsWe included 235 patients (51.5% female) aged 73.5±10.7 years. Ninety-six patients have reduced LVEF (40.8%), 41 mildly reduced (17.4%), and 98 preserved (41.7%). Patients with preserved LVEF have more anaemia (42.6% vs 26.8% vs 52.6%; P=.02). Less than 50% of patients received the correct dose of FCM, especially patients with preserved LVEF (P=.004). One patient (0.4%) presented a local exanthema with no other adverse effects. At 3 months, all analytical parameters significantly improved, except haemoglobin (12.9 vs 13.0mg/dL; P=.95) and natriuretic peptides (3261 vs 3471pg/mL; P=.56) in mildly reduced LVEF patients. The functional class did not improve in preserved LVEF patients, but it did in the rest. ConclusionsFCM is safe and effective in correcting ID in HF patients regardless of LVEF. Natriuretic peptides are reduced in all patients except those with mildly reduced LVEF. Functional class improvement is less likely in patients with preserved LVEF.

Incidence and predictors of hypophosphataemia after ferric carboxymaltose use-A 3-year experience from a single institution in Singapore.

Ferric carboxymaltose (FCM) administration helps reduce transfusion requirements in the perioperative situation, which improves patient outcomes and reduces healthcare costs. However, there is increasing evidence of hypophosphataemia after FCM use. We aim to determine the incidence of hypophosphataemia after FCM administration and elucidate potential biochemical factors associated with the development of subsequent hypophosphataemia. A retrospective review of anonymised data of all FCM administrations in a single institution was conducted from August 2018 to August 2021. Each unique FCM dose administered was examined to assess its effect on Hb and serum phosphate levels within the subsequent 28 days from each FCM administration. Phosphate levels were repeatedly measured within the 28-day interval and the lowest phosphate level within that period was determined. Patients' serum phosphate levels within 28 days of FCM administration were compared against normal serum phosphate levels within 2 weeks before FCM administration. The odds ratios of various pre-FCM serum markers were calculated to elucidate potential biochemical predictors of post-FCM hypophosphataemia. In 3 years, a total of 1296 doses of FCM were administered to 1069 patients. The mean improvement in Hb was 2.45 g/dL (SD = 1.94) within 28 days of FCM administration, with the mean time taken to peak Hb levels being 6.3 days (SD = 8.63), which is earlier than expected, but was observed in this study and hence reported. The incidence of hypophosphataemia <0.8 mmol/L was 22.7% (n = 186), and <0.4 mmol/L was 1.6% (n = 9). This figure is lower than the numbers reported in previously published meta-analyses given that routine checks of serum phosphate levels were not conducted initially and hence could possibly be higher. The odds of developing hypophosphataemia (<0.8 mmol/L) were 27.7 (CI: 17.3-44.2, p < 0.0001) if baseline serum phosphate was less than 1 mmol/L. The odds of developing hypophosphataemia (<0.8 mmol/L) were 1.3 (CI: 1.08-1.59, p < 0.01) if the change in Hb levels observed after FCM administration were more than 4 g/dL. Hypophosphataemia after FCM administration is significant and FCM should be used by clinicians with caution.

Incidence, evolution and risk factors of hypophosphatemia in patients with solid tumors receiving ferric carboxymaltose: a retrospective cohort study

ABSTRACT Objectives Ferric carboxymaltose (FCM) is increasingly used in the management of cancer-related anemia, yet it may cause hypophosphatemia. This retrospective study describes the incidence, evolution and risk factors of hypophosphatemia in a cohort of patients with solid tumors receiving FCM. Methods Serum phosphorus concentration was assessed longitudinally using a random intercepts model. The probability of developing hypophosphatemia, as graded by CTCAE version 4.0, was investigated using a multi-state model. Transition hazards were modeled non-parametrically and semi-parametrically by a Cox model. Causal marginal risk differences between baseline interventions on serum phosphorus and/or FCM dose were obtained via G-computation. Results In 174 ambulatory patients with solid tumors receiving FCM at two university hospitals between October 2020 and September 2021, the risk of developing moderate-to-severe hypophosphatemia was 36.0% (95% confidence interval (CI) 28.2–43.9%) and peaked within 16 days after first FCM administration. The average duration of moderate-to-severe hypophosphatemia was 12.4 days. After adjustment for confounders, lower baseline serum phosphorus (adjusted hazard ratio (aHR) 0.88 per 0.1 mmol/L increase, 95% CI 0.79–0.98) and higher FCM dose (first dose: aHR 1.12 per 1 mg/kg increase, 95% CI 1.01–1.25; second dose: aHR 1.06 per 1 mg/kg increase, 95% CI 1.00–1.13) significantly increased the hazard of moderate-to-severe hypophosphatemia. Conclusion Approximately one out of three ambulatory patients with solid tumors may develop moderate-to-severe hypophosphatemia after FCM administration. Baseline serum phosphorus and FCM dose may be modifiable risk factors that should be considered for intervention in order to mitigate the risk of hypophosphatemia.

Retrospective Assessment of Total Cost of Care in Non-Dialysis Dependent Chronic Kidney Disease Patients Receiving Parenteral Iron Therapy for Iron Deficiency Anemia

Introduction Iron deficiency anemia (IDA) is a common comorbidity among patients with chronic kidney disease. Iron deficiency occurs in 15% to 48% of non-dialysis dependent chronic kidney disease (ND-CKD) patients with anemia. Parenteral iron therapy is often required in ND-CKD patients with IDA who cannot tolerate or are nonresponsive to oral iron. Available IV iron treatments vary in the amount of iron dose per administration, the number of infusions required to achieve complete iron repletion and drug acquisition cost. The objective of this study was to compare healthcare costs between ferric carboxymaltose (FCM) and low dose IV iron (LDI) for the treatment of IDA in ND-CKD patients. Methods Medical and pharmacy claims from IQVIA PharMetrics® Plus data were analyzed. Adult patients who received first (index) dose of FCM or LDI (i.e., iron sucrose, iron dextran, sodium ferric gluconate complex in sucrose) from 2017 to 2019 were included. Eligible patients were required to be continuously eligible 6 months before (baseline) and 12 months after index IV iron infusion and had medical claims associated with diagnosis of chronic kidney disease (ICD-10: N18.1 to N18.5) and IDA (ICD-10: D50.x) anytime during the 18-month study observation period. In addition, eligible FCM patients were required to receive a second dose of FCM within 21 days of index date. Patients who had claims associated with end stage renal disease (ICD-10: N18.5 and N18.6) or dialysis (HCPCS CPT code: 90935-90999) and patients who had received other IV iron products in the 6-month baseline period were excluded. Unadjusted mean number of IV iron infusions, outpatient visits and hospital admissions in the 6 months before and 12 months following index IV iron dose were summarized on a per-patient-per-month basis. Post-index monthly inpatient, outpatient, and total healthcare costs for FCM and LDI were compared using generalized linear model with gamma log-link adjusting for pre-index monthly cost, age, gender, year of index treatment and the Charlson Comorbidity Index (CCI). Sensitivity analyses comparing FCM versus iron sucrose were performed. Results Data from 3,727 FCM patients [mean (SD) age= 67.9 (13.8) years, 61% females, CCI (SD)=1.9 (2.5)] and 5,068 LDI patients [mean (SD) age=64.8 (15.0) years, 60% females, CCI (SD)=1.6 (2.4)] were analyzed. Within the LDI cohort, 3,489 patients received index iron sucrose treatment [mean (SD) age=64.6 (15.1) years, 60% females, CCI (SD)=1.5(2.4)]. Mean (SD) number of IV iron infusions was 0.24 (0.26) for FCM, 0.43 (0.52) for LDI and 0.46 (0.52) for iron sucrose during the post-index period. During the post-index period, FCM has a smaller increase in the number of outpatient visits (mean change from baseline=0.13) than LDI (mean change from baseline=0.64) and iron sucrose (mean change from baseline=0.70). The number of hospital admissions in the post-index period were numerically lower for FCM (mean change from baseline=-0.05) but numerically higher for LDI (mean change from baseline=0.04) and iron sucrose (mean change from baseline=0.05). Mean total health care cost increased during the 12-month period after IV iron treatment compared to baseline in all treatment groups. After adjusting for pre-index cost and other covariates, FCM treatment was associated with significantly lower post-index inpatient costs [adjusted cost ratio (ACR)= 0.73, p<0.0001], ER costs (ACR=0.76, p<0.0001), outpatient costs (ACR=0.73, p<0.0001) and total costs (including IV iron) (ACR = 0.81, p<0.0001) than LDI. Similar results were observed in the comparisons between FCM and iron sucrose. Conclusion Higher drug acquisition cost of FCM compared to LDI was primarily offset by lower inpatient and outpatient costs during the 12 months after FCM treatment for IDA in ND-CKD patients than LDI, resulting in significantly lower overall total health care cost for FCM compared to LDI. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Patient Reported Outcomes after Ferric Carboxymaltose Treatment for Iron Deficiency Anemia: A Prospective Observational Study

Objective: Fatigue is a common symptom reported by iron deficiency anemia (IDA) patients. Iron deficiency has also been shown to reduce physical function independent of anemia. Parenteral iron therapy is indicated for the treatment of iron deficiency anemia (IDA) in patients who are intolerant or nonresponsive to oral iron. This study assessed fatigue symptoms and patient-reported functioning in IDA patients for up to 6 months after treatment with ferric carboxymaltose (FCM). Methods: This prospective, single arm, longitudinal observational study included adult patients diagnosed with IDA who were prescribed FCM under routine clinical care across 7 clinical practice sites in US. Eligible patients had baseline serum hemoglobin of >7 g/dL and <13 for males or <12 for females, no potential contraindications to FCM, and no parenteral iron therapy within 3 months before study enrollment. Patients completed patient-reported outcome (PRO) questionnaires prior to receiving FCM treatment, and at 3 months and 6 months after the first course of FCM. PROs included the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) scale, the Patient Reported Outcomes Measurement and Information System (PROMIS) Physical Function v2.0 Short Form, and the PROMIS Global Health v1.2 Short Form (physical and mental health). A higher FACIT-Fatigue or a lower PROMIS Physical Function, PROMIS Global Physical Health or Mental Health score indicate more health problems. For each measure, a mean change from baseline of ≥5 points was considered clinically meaningful. Associations between baseline serum hemoglobin and each PRO score were assessed using Spearman's rank correlation coefficient. Results: 152 patients with median IDA history of 2.0 years were included in the intent-to-treat population (mean age=47.4 ± 16.0 years, 82.2% females, 17.1% with inflammatory bowel disease, 13.8% with abnormal uterine bleeding, 9.2% with cancer, mean baseline serum Hgb =10.19±1.35 g/dL). About one-third of patients (34.9%) had oral iron treatment and 2.6% had a blood transfusion within 3 months prior to FCM treatment. A small proportion of patients (6.6%) had parenteral iron treatment in the 12 months before study enrollment. Most patients (83.6%) were prescribed 2 doses of FCM (total dose of 1500mg) at baseline. Within 6 months after the first course of FCM, no patient received treatment with erythropoietin stimulating agents, 1 patient received a blood transfusion, and 14 (9.7%) patients required additional IV iron treatment after the initial course of FCM treatment prescribed at baseline. Median time from baseline to additional IV treatment was 86.5 days. Fatigue symptoms were improved after FCM treatment, as indicated by significantly lower mean FACIT-Fatigue scores at 3 months (50.19 ± 9.51) and at 6 months (52.42 ± 9.31) compared to baseline (61.01 ± 8.96), with p<0.0001 each. A majority of patients had a reduction of at least 5 points in FACIT-Fatigue score from baseline to 3 months (72.7%) and 6 months (67.3%), respectively. Physical function also improved, as indicated by significantly higher mean PROMIS Physical Function score at 3 months (46.08 ± 8.52) and 6 months (45.15±8.85) compared to baseline (41.31±8.63), with p<0.0001 each. Improvements in PROMIS Global Physical Health (p<0.0001) and the PROMIS Global Mental Health score (p=0.0027) were also observed at 3 months and 6 months compared to baseline. Correlations between baseline serum hemogloblin levels and PRO scores were borderline to highly significant, with correlation coefficients of 0.151 (p=0.0647) with PROMIS Global Mental Health, 0.276 (p=0.0006) with Global Physical Health, 0.286 (p=0.0004) with PROMIS Physician Function and -0.294 (p=0.0002) with FACIT-Fatigue. Conclusions: IDA patients treated with FCM reported significant reduction in fatigue symptoms and improvements in physical function, physical health and mental health at 3 months after treatment. These benefits were sustained at 6 months after treatment, with only a small proportion of patients requiring re-treatment with additional IV iron beyond the initial course of FCM treatment. Significant correlations between serum Hgb and PRO scores observed in this study suggest that data collected directly from patients in a real-world setting can provide a valuable supplement to traditional clinical outcomes for evaluating treatment effectiveness. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

IRON DEFICIENCY MANAGEMENT IN HYPERTENSIVE SUBJECTS WITH ACUTE HEART FAILURE: FROM CLINICAL TRIALS TO CLINICAL PRACTICE

Objective: Iron deficiency (ID) is common in heart failure (HF) and independently increases the risk of re-hospitalisation for HF. Intravenous ferric carboxymaltose (FCM) has been shown to improve symptoms and quality of life in patients with chronic HF and ID deficiency. We aimed to evaluate the effect of FCM on outcomes in hypertensive patients (HTs) who were stabilised after an episode of acute HF. Design and method: From november 2020 to july 2021, in 148 HTs consecutively admitted in our Hypertension Unit for acute HF with ejection fraction &lt; 50%, a ID was found in 39 of them (51% men, mean age 71.1 ± 18.5 yrs). ID was defined as serum ferritin &lt; 100ng/mL or serum ferritin 100–299ng/mL with transferrin saturasion &lt; 20%. Before hospital discharge, HTs received FCM dose according to the extent of ID and then reapeated it at 4-week interval. The primary outcome was to assess first HF hospitalisation or cardiovascular (CV) death at 4 and at 12 weeks after discarged. The analysis of variance for repeated measures assesed the differences in the values of systolic blood pressure (SBP), diastolic blood pressure (DBP), N-terminal pro-B-type-natriuretic peptide (NT-pro-BNP, (in pg/mL) and haemoglobin (in g/L) from baseline to the follow-up (FU). Results: At 4 and 12-week SBP and DBP values were not different from baseline (123.2 ± 13.8 and 124.4 ± 13.2 vs. 124.1 ± 14.1, NS and 70.9 ± 9.8, 71.0 ± 10.0 vs. 71.8 ± 10.2 mmHg, NS, respecively). NT-pro-BNP values significantly decreased from baseline to the FU (8.100 ± 8.132 vs. 6.244 ± 4.280 and 4.126 ± 3.485, p &lt; 0.05). Haemoglobin values significantly increased from baseline to the FW (9.5 ± 1.2 vs. 11.9 ± 1.3 and 12.2 ± 1.4, p &lt; 0.005). At 4-week no patient was re-admitted for HF, while at the 12-week a re-hospitalisation was observed in 17,9% of cases. No CV death was observed during the FW. Conclusions: Administration of FDC is effective to prevent first HF re-hospitalization and as recommended in 2021 ESC HF-guidelines, iron supplementation with FDC should be considered for the reduction of HF re-hospitalizations also in HTs with LVEF &lt; 50% recently hospitalized for worsening HF. However, our results must be confirmed in studies involving a greater number of subjects, and with a longer FW.

Ferric Carboxymaltose Improves the Quality of Life of Patients with Inflammatory Bowel Disease and Iron Deficiency without Anaemia.

Background: Iron deficiency (ID) without anaemia is a common comorbidity associated with inflammatory bowel disease (IBD) that has a negative impact on health-related quality of life (HRQoL). Methods: This multicentre, prospective, observational study examined the response to, safety of and impact on HRQoL of a single 500 mg dose of intravenous ferric carboxymaltose (FCM) in patients with IBD and ID without anaemia. The diagnostic criteria for ID were low serum ferritin (<30 µg/L in the absence of inflammatory activity or <100 µg/L with inflammation) and transferrin saturation index (TSAT) < 16%. The effect on iron levels and HRQoL, according to the health status questionnaires SF-12v2 and EQ-5D, was evaluated 1 month after FCM infusion in an outpatient setting. Results: Of the 105 patients who received FCM, 98 patients completed the study. After 1 month, a single dose of FCM significantly increased serum ferritin, serum iron and TSAT. Importantly, patients reported fewer ID symptoms and problems on all EQ-5D dimensions. They also had higher EQ-5D visual analogue scale and SF-12v2 scores after treatment. FCM had similar clinical effects on men and women and on patients with Crohn’s disease (n = 66) and ulcerative colitis (n = 32). Conclusion: A single dose of FCM rapidly restored iron parameters and significantly improved patients’ symptoms and HRQoL at 1 month after treatment.

MO526: Renal Function in Patients With Non-Dialysis Kidney Disease Treated With Ferric Carboxymaltose

Abstract BACKGROUND AND AIMS Iron deficiency anemia occurs in most patients with non-dialysis chronic kidney disease (ND-CKD). Several studies have suggested the efficacy and safety of ferric carboxymaltose (FCM) in this group of patients, but none have shown a positive impact on renal function. The aim our study was to investigate the impact of FCM on renal function in ND-CKD patients. METHOD Prospective observational study of ND-CKD stages 3 to 5 patients, with anemia and iron deficiency [ferritin level &amp;lt;100 µg/L or &amp;lt;200 µg/L with transferrin saturation (TSAT) &amp;lt;20%], treated with FCM from 01 January 2019 to 31 June 2021. FCM was administrated as a single IV infusion. Patients were categorized into two cohorts according to the dose of FCM received: 500 mg or 1000 mg. Clinical and analytical data were compared among groups at baseline and 24 weeks after infusion. Renal function was assessed using estimated glomerular filtration rate (eGFR), calculated using the CKD-EPI formula. Statistical analysis was executed using SPSS (Version 23 for Mac OSX). RESULTS The mean age of 140 patients was 77.31 ± 9.68 years, 62 (44.3%) were male, 86 (61.4%) were diabetic, 84 (60%) had congestive heart failure and 121 (86.4%) had hypertension. Thirty-five (25%) patients had CKD stage 3, 74 (52.9%) had stage 4 and 31 (22.1%) had stage 5. Seventy-eight (55.7%) patients were treated with 1000 mg of FCM. There were no gender, comorbidity, CKD etiology or stage differences among groups. Patients treated with 1000 mg were younger (74.36 ± 13.59 versus 78.44 ± 9.28 years, P = .046). At baseline, mean Hb was 10.4 ± 1.35, 10.27 ± 1.47 and 10.54 ± 1.2 g/dL and mean eGFR was 26.18 ± 17.167, 23.55 ± 4.17 and 28.71 ± 19.43 mL/min/1.73 m2 for the whole group, 1000 mg and 500 mg cohorts. At 24 weeks, Hb showed an increase of 1.24 ± 1.78 (P = .001), 1.54 ± 1.99 (P = .001) and 0.86 ± 1.4 g/dL (P = .001), and eGFR an increase of 1.13 ± 6.49 (P = .041) and 1.55 ± 6.87 mL/min/1.73 m2 (P = .049) for the whole group and 1000 mg cohort, but not 500 mg cohort. A Pearson correlation was performed and revealed a positive correlation between the variation of Hb and eGFR during the study follow-up period (r = .283, P = .001 and r = .310, P = .008) in the same groups. CONCLUSION In addition to the effectiveness in correcting iron deficiency anemia in patients with ND-CKD, our results suggest a positive impact on renal function of higher doses of FCM after 6 months of administration.

Short-term treatment of iron deficiency anemia after cardiac surgery.

Iron deficiency anemia (IDA) is frequent after cardiac surgery and is associated with increased morbidity and mortality. In a retrospective study, we analyzed 106 patients with IDA (hemoglobin [Hb] ≤ 12 g/dl in women and ≤ 13 g/dl in men, transferrin saturation [TSAT] ≤ 20%) on admission to a Cardiac Rehabilitation Unit after cardiac surgery. The patients were divided into two groups, one was treated with oral sucrosomial iron (SI) and the other with intravenous ferric carboxymaltose (FCM). Patients received a single 1000 mg dose of FCM from the day after admission to rehabilitation (T1), or a 120 mg/day dose of SI from T1 until discharge (T2); after discharge, SI was reduced to 30 mg/day until the end of follow-up (T3). Hb was evaluated at T1, T2 and T3; the other hematological parameters at T1 and T3; natriuretic peptides at T1, T2 and T3; 6-minute walk test (6MWT) at T1 and T2. Folate, vitamin B12 and reticulocytes were sampled on admission. Folate deficiency was documented in 60.4% of patients. Hb increased in both groups with no significant differences between the two treatments (p = 0.397). The other iron metabolism parameters (sideremia, transferrin, TSAT) displayed similar behavior, showing a significant increase at T3 (p < 0.001) with both therapies, although the increase was faster with FCM. Ferritin – high on admission – decreased at T3 in the SI group and rose significantly in the FCM group (SI 219.5 vs. FCM 689 ng/ml p < 0.0001). The 6MWT increased significantly at T2, with an overlap between SI and FCM. In conclusion, the results of this study show that SI and FCM exhibit the same effectiveness on IDA; the response time to therapy of both treatments is also equally fast. SI and FCM induce a similar increase in functional capacity. The study shows that SI can be a viable alternative to FCM after cardiac surgery in terms of effectiveness and tolerability.

Intravenous Iron-Induced Hypophosphatemia: An Emerging Syndrome.

Some, but not all, intravenous iron formulations have been recognized to induce renal phosphate wasting syndrome. Most commonly this has been reported following treatment of iron deficiency anemia (IDA) with ferric carboxymaltose (FCM). A search of PubMed identified relevant randomized controlled trials (RCTs), and case studies evaluating hypophosphatemia (HPP) resulting from intravenous iron treatment. While more recent larger comparative RCTs have confirmed that the majority of patients receiving FCM, especially those with normal renal function, may experience severe HPP, complete documentation is hampered by inconsistent reporting of serum phosphate in such trials. Similarly, while case series and RCTs have documented the persistence of HPP for several weeks or even months, the lack of studies lasting beyond 5–6 weeks has constrained full understanding of the duration of effect. Clinical trials have established that the mechanism involves the bone/metabolic axis with the elevation of intact fibroblast growth factor 23 playing the central role. Reports continue to accumulate of the clinical consequences of severe HPP which are, most commonly, bone abnormalities following repetitive dosing. Case reports and studies, however, have also shown that symptomatic hypophosphatemia can occur after a single FCM dose. The frequency of such events remains unknown, in part due to lack of awareness of hypophosphatemia coupled with the fact that the most common acute symptoms of HPP (fatigue and weakness) are the same for IDA and for many of the chronic diseases that cause IDA. Changes to US and European prescribing information for FCM should raise awareness of the potential for HPP and need to monitor patients at risk for it.

MO557EFFICIENCY OF FERRIC CARBOXYMALTOSE IN NON-DIALYSIS CKD PATIENTS AND ITS IMPACT ON KIDNEY FUNCTION: A PROSPECTIVE OBSERVATIONAL STUDY

Abstract Background and Aims Iron deficiency anemia occurs in the vast majority of patients with chronic kidney disease (CKD). The aim of this study was to investigate the efficacy of ferric carboxymaltose (FCM) iron deficiency anemia’s treatment in non-dialysis CKD patients and to clarify its impact on kidney function. Method Prospective observational study of non-dialysis CKD stage 3 to 5 patients, with anemia and iron deficiency treated with FCM from 01 January 2019 to 31 June 2020. FCM was administrated as a single IV infusion of 500mg or 1000mg. Baseline clinical, analytical and demographic data were recorded. FCM efficacy was evaluated by comparing hemoglobin (Hb), serum ferritin and transferrin saturation index (TSAT) 24 ± 8 weeks after the infusion with analytical values at baseline. Renal function was also assessed at baseline and at 24 ± 8 weeks using estimated glomerular filtration rate (eGFR), calculated by CKD-EPI formula. Statistical analysis was executed using SPSS (Version 23 for Mac OSX). Results The average age of 71 patients was 77.31 ± 9.68 years, 29 (40.8%) were male, 46 (64.8%) were diabetic and 41 (57.8%) had congestive heart failure. Sixteen (22.5%) patients had CKD stage 3, 41 (57.7%) stage 4 and 14 (19.7%) stage 5. Twenty-five (35.2%) patients were treated with 1000mg of FCM. At baseline, average hemoglobin level (Hb) was 10.16 ± 1.12g/dL, serum ferritin 83.25 ± 96.55µg/L, TSAT 14.48 ± 6.72mg/dL and eGFR 24.21± 13.09ml/min/1.73m2. At 24 ± 8 weeks, Hb showed an increase of 1.31 ± 1.49 g/dL (p=0.001) and TSAT 10.68 ± 10.40% (p=0.001). Serum ferritin showed also an increase of 4.75 ± 180.53µg/L but did not reach statistical significance. The increase in Hb was observed uniformly across all stages of CKD. A Pearson correlation revealed a positive correlation between the variation of Hb and eGFR during the study follow-up period (r=0.310, p=0.008). A subgroup analysis was performed, patients were classified in 2 groups according to FCM dose. At baseline, there was no age, comorbidities or eGFR difference among groups. Patients treated with 1000mg had lower Hb (p=0.03) and serum ferritin (p=0.01). At 24±8 weeks both groups showed increases in Hb (p=0.001) and TSAT (p=0.001). Patients treated with 1000mg showed also a significant increase in ferritin (p=0.004). The Pearson correlation confirmed a positive correlation between the variation of Hb and eGFR in the group of patients treated with 1000mg (r=0.467, p=0.019) but not in the group treated with 500mg. Conclusion FCM was effective in the treatment of iron deficiency anemia in non-dialysis CKD stage 3 to 5 patients. In our population, the increase of Hb levels correlated with an improvement in eGFR in patients treated with higher doses of FCM, suggesting a positive impact of FCM on kidney function.

584 Response to Intravenous Ferric Carboxymaltose in the Treatment of Childhood Restless Legs Syndrome/Periodic Limb Movement Disorder

Abstract Introduction Pediatric Restless Legs Syndrome (RLS)/Periodic Limb Movement Disorder (PLMD) are treatable disorders affecting quality of life. The first line therapy is oral iron, which may have gastrointestinal side effects or suboptimal absorption. Consequently, parenteral iron preparations are needed, but have been insufficiently studied in children. This study evaluates the response to intravenous ferric carboxymaltose (FCM) in pediatric RLS/PLMD. Methods We performed a retrospective chart review of children who received FCM between May 2018 and January 2019 for treating RLS/PLMD. Serum ferritin before and after the infusion were compared. Where possible, the Clinical Global Impressions of Improvement (CGI-I) was evaluated. Side effects documented in the charts were extracted. The median administered dose of FCM was 10.1 mg/kg (range 9.6–20.8) over 0.6 to2 hours. Results There were 27 patients, with mean age of 10.0 +/-4.2 years. 52% were female. 24 had RLS and 3 had PLMD. 20/27 (69.7%) had prior oral iron therapy; 4/20 (26.0%) experienced side effects. Adverse events from FCM infusion included procedure-related anxiety in 4/27, nausea in 1/27, infusion site pain in 2/27, and tachycardia in 1/27. One patient developed subcutaneous extravasation of iron with brownish skin discoloration and a resulting adjustment disorder. Three patients had phosphorus checked following infusion; all were normal. Serum ferritin was available both before and after the infusion for 17 patients. Mean serum ferritin prior to infusion was 27.2 +/-15.7 µg/L (range 6–58) and after the infusion it was 109.8 +/-49.34 µg/L (range 27–192). Mean ferritin increase was 82.6 +/-41.5 µg/L (range 14–160; p=0.0001). Post-infusion ferritin was over 50 µg/L for all but 2 of the subjects, with follow up ranging from 31–266 days (mean 120 days). A larger increase was seen at higher doses (p=0.01). Ferritin increase was not impacted by age, gender, symptom severity, PLMI or prior ferritin level. CGI-I was applied to 15 patients with sufficient follow-up documentation and showed improvement in 86%, with 79% much or very much improved. Conclusion The administration of FCM in children with RLS/PLMD is associated with a satisfactory rise in serum ferritin and modest symptomatic improvement. Support (if any):

Intravenous Iron Replacement in Patients with Left Ventricular Assist Devices

<h3>Purpose</h3> In patients supported by LVADs, iron deficiency is a common cause of anemia (IDA) and its associated morbidity. The clinical benefits of intravenous (IV) iron replacement in heart failure are well described, but there are fewer data supporting IDA treatment in LVAD patients. This study assessed the clinical and financial impact of IV ferric carboxymaltose (FCM) in an outpatient LVAD population through evaluation of anemia, blood transfusion requirements, readmissions, and insurance reimbursement. <h3>Methods</h3> This was a single-center prospective observational study of LVAD patients with IDA (ferritin <100 ng/mL or 100-300 ng/mL with Tsat <20%). Outpatients received FCM 750 mg x 2 doses given 1 week apart. The primary endpoint was the resolution of anemia at 1, 3, and 6 months. Blood transfusion requirements and readmissions were assessed pre- and post-FCM therapy. Financial analysis included the comparison of drug-specific reimbursement to drug acquisition cost. <h3>Results</h3> Eighty patients received FCM therapy. Baseline data are shown in Table 1. On average, patients were 19 months post-implant, 16% had experienced a gastrointestinal bleed within the last 3 months, and mean baseline Hgb was 9.9 g/dL. At 1 month, mean Hgb significantly improved (12.0±1.9 g/dL vs 9.9±1.4, p<0.0001), and this was maintained at 3 months (12.1±2.0, p<0.0001) and 6 months (12.2±2.1, p<0.0001) (Figure 1). When comparing the 3- and 6-month periods pre- and post-FCM, blood transfusion requirements and hospital admissions were both significantly reduced (Table 3). The majority of patients were covered by Medicare (67.5%) or a commercial payor (18.2%) with drug reimbursement to cost ratios of 0.81 and 1.97, respectively. <h3>Conclusion</h3> This prospective evaluation of IV iron replacement with 2 doses of FCM in a large cohort of LVAD patients demonstrated a resolution of anemia and subsequent reduction in blood transfusion and readmission requirements. In a mixed payor patient population, drug reimbursement supports utilization of FCM for this indication.

Predictors of clinical improvement in heart failure patients with iron deficiency treated with ferric carboxymaltose

Introduction and objectivesIntravenous iron is recommended to correct iron deficiency in heart failure (HF) patients, although not all patients had the same response. We evaluated the impact of ferric carboxymaltose (FCM) in analytical and clinical improvement and analyzed the response according to different parameters. MethodsWe included HF patients who received FCM in the daily hospital to correct iron deficiency. We recorded clinical and analytical parameters at baseline and 3 months follow-up. ResultsWe included 236 patients (age 73.5±10.7 years) with left ventricular ejection fraction 44.5±15.3%. There were no adverse effects during the infusion. All ferric analytical parameters significantly increased at 3 months. 25.1% of patients improved functional class, and New York Heart Association (NYHA) III patients were more likely to improve. Mean corpuscular volume predicted NYHA improvement (OR, 0.97; 95%CI, 0.93–1.00; P=.05). Body mass index (OR, 0.86; 95%CI, 0.78–0.95; P=.002) and ferritin (OR, 1.00; 95%CI, 1.00–1.01; P=.042) were also predictors of N-terminal pro-B-type natriuretic peptide reduction of at least 30% from basal levels. 61.3% received lower doses of FCM than the theoretical ones, and those with the correct dose were more likely to improve NYHA and reduce natriuretic peptides. ConclusionsFCM was useful to correct iron deficiency in clinical practice, independently to anemia, without relevant adverse effects. Clinical improvement was especially relevant in more symptomatic patients and those with absolute deficiency. Mean corpuscular volume, body mass index, ferritin, and dose of FCM were predictors of clinical improvement.

Ferric Carboxymaltose Across All Ages in Paediatric Gastroenterology Shows Efficacy Without Increased Safety Concerns.

The aim of the study was to assess the efficacy, safety and side-effect profile of ferric carboxymaltose (FCM) for correcting IDA in children and adolescents in paediatric gastroenterology, hepatology, and nutrition. This was a retrospective study of all gastroenterology patients <18 years who had FCM (October 2015 to October 2017). Haematological and biochemical parameters were recorded pre-infusion, at 4 weeks, 3 months, 6 months, and 1 year post-infusion. Recognised side-effects were documented. Sixty-six children received FCM during this period. Data was analysed on 61 children, 5 excluded because of inadequate data. The median age at administration was 14 years (IQR 7). Thirty-two (52%) were boys. Twenty-six (42%) were <14 years old. Seven (11.5%) were <5 years old. Seventeen (28%) were switched from oral iron supplements to FCM. The median dose of FCM delivered was 19 mg/kg. The median haemoglobin increased from 108 to 126 g/L at 1 month post-infusion (P value <0.00001). The mean cell volume also improved from 80 to 84 fL at 1 month post-infusion (P value = 0.0007). Forty-eight (94%) children corrected their anaemia after receiving FCM. Two patients (3%) reported side-effects with skin bruising and staining. FCM appears to be effective in correcting IDA in children across a wide range of gastroenterology indications and all ages. It is effective and generally well tolerated including in very young patients. Potential side-effects can be avoided by careful monitoring during infusions.