title: Ferric carboxymaltose in patients with iron-deficiency anemia and impaired renal function: the REPAIR-IDA trial. A randomized controlled trial comparing intravenous ferric carboxymaltose with oral iron for treatment of iron deficiency anaemia of non-dialysis-dependent chronic kidney disease patients Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin concentration. Evaluation of a Single Dose of Ferric Carboxymaltose in Fatigued, Iron-Deficient Women – PREFER a Randomized, Placebo-Controlled Study Iron Deficiency Generates Secondary Thrombocytosis and Platelet Activation in IBD: the Randomized, Controlled ThromboVIT Trial Combination of direct and indirect evidence in mixed treatment comparisons. Cost-effectiveness analysis of ferric carboxymaltose in iron-deficient patients with chronic heart failure in Sweden A randomized, double-blind, placebo-controlled trial of intravenous iron sucrose in restless legs syndrome. Safety and tolerability of intravenous ferric carboxymaltose in patients with iron deficiency anemia Comparative efficacy and safety of intravenous ferric carboxymaltose in the treatment of postpartum iron deficiency anemia. A Novel Intravenous Iron Formulation for Treatment of Anemia in Inflammatory Bowel Disease: The Ferric Carboxymaltose (FERINJECT®) Randomized Controlled Trial Ferric carboxymaltose prevents recurrence of anemia in patients with inflammatory bowel disease. Intravenous Ferric Carboxymaltose Compared With Oral Iron in the Treatment of Postpartum Anemia: A Randomized Controlled Trial A Randomized Controlled Trial of Oral versus Intravenous Iron in Chronic Kidney Disease Ferric carboxymaltose injection in the treatment of postpartum iron deficiency anemia: a randomized controlled clinical trial. Large-dose intravenous ferric carboxymaltose injection for iron deficiency anemia in heavy uterine bleeding: a randomized, controlled trial. Intravenous iron reduces NT-pro-brain natriuretic peptide in anemic patients with chronic heart failure and renal insufficiency. FERGIcor, a randomized controlled trial on ferric carboxymaltose for iron deficiency anemia in inflammatory bowel disease. Iron deficiency and its management in patients undergoing lipoprotein apheresis. Comparison of two parenteral iron formulations. Hepcidin levels predict nonresponsiveness to oral iron therapy in patients with iron deficiency anemia Sodium ferric gluconate complex in hemodialysis patients. II. Adverse reactions in iron dextran-sensitive and dextran-tolerant patients.
abstract: BACKGROUND Iron-deficiency anemia in non-dialysis-dependent chronic kidney disease ( NDD-CKD ) frequently requires parenteral iron replacement , but existing therapies often require multiple administrations . We evaluated the efficacy and cardiovascular safety of ferric carboxymaltose ( FCM ) , a non-dextran parenteral iron permitting large single-dose infusions , versus iron sucrose in patients with iron-deficiency anemia and NDD-CKD . METHODS A total of 2584 participants were r and omized to two doses of FCM 750 mg in one week , or iron sucrose 200 mg administered in up to five infusions in 14 days . The primary efficacy endpoint was the mean change to highest hemoglobin from baseline to Day 56 . The primary composite safety endpoint included all-cause mortality , nonfatal myocardial infa rct ion , nonfatal stroke , unstable angina , congestive heart failure , arrhythmias and hyper- and hypotensive events . RESULTS The mean hemoglobin increase was 1.13 g/dL in the FCM group and 0.92 g/dL in the iron sucrose group ( 95 % CI , 0.13 - 0.28 ) . Similar results were observed across all subgroups , except Stage 2 CKD . More subjects in the FCM group achieved a hemoglobin increase of ≥ 1.0 g/dL between baseline and Day 56 ( 48.6 versus 41.0 % ; 95 % CI , 3.6 - 11.6 % ) . There was no significant difference between FCM and iron sucrose recipients with respect to the primary composite safety endpoint , including the major adverse cardiac events of death , myocardial infa rct ion , or stroke . A significant difference in the number of protocol -defined , predominantly transient hypertensive episodes was observed in the FCM group . CONCLUSIONS Two 750-mg infusions of FCM are a safe and effective alternative to multiple lower dose iron sucrose infusions in NDD-CKD patients with iron-deficiency anemia Background . Iron deficiency is a common cause of anaemia and hyporesponsiveness to erythropoiesis-stimulating agents ( ESAs ) in non-dialysis-dependent chronic kidney disease ( ND-CKD ) patients .  Current intravenous iron agents can not be administered in a single high dose because of adverse effects . Ferric carboxymaltose , a non-dextran parenteral iron preparation , can be rapidly administered in high doses . Methods . This open-label trial r and omized 255 subjects with glomerular filtration rates ≤ 45 mL/min/1.73 m2 , haemoglobin ≤ 11 g/dL , transferrin saturation ≤ 25 % , ferritin ≤ 300 ng/mL , and stable ESA dose to either intravenous ferric carboxymaltose 1000 mg over 15 min ( with up to two additional doses of 500 mg at 2-week intervals ) or oral ferrous sulphate 325 mg thrice daily for a total of 195 mg elemental iron daily for 56 days . Results . In the modified intent-to-treat population , the proportion of subjects achieving a haemoglobin increase ≥ 1 g/dL at any time was 60.4 % with ferric carboxymaltose and 34.7 % with oral iron ( P < 0.001 ) . At Day 42 , mean increase in haemoglobin was 0.95 ± 1.12 vs 0.50 ± 1.23 g/dL ( P = 0.005 ) , mean increase in ferritin was 432 ± 189 ng/mL vs 18 ± 45 ng/mL ( P < 0.001 ) and mean increase in transferrin saturation was 13.6 ± 11.9 % vs 6.1 ± 8.1 % ( P < 0.001 ) . Treatment-related adverse events were significantly fewer with ferric carboxymaltose than with oral iron ( 2.7 % and 26.2 % , respectively ; P < 0.0001 ) . Conclusions . We conclude that 1000 mg ferric carboxymaltose can be rapidly administered , is more effective and is better tolerated than oral iron for treatment of iron deficiency in ND-CKD patients This is the first study to investigate the efficacy of intravenous iron in treating fatigue in nonanemic patients with low serum ferritin concentration . In a r and omized , double-blinded , placebo-controlled study , 90 premenopausal women presenting with fatigue , serum ferritin ≤ 50 ng/mL , and hemoglobin ≥ 120 g/L were r and omized to receive either 800 mg of intravenous iron (III)-hydroxide sucrose or intravenous placebo . Fatigue and serum iron status were assessed at baseline and after 6 and 12 weeks . Median fatigue at baseline was 4.5 ( on a 0 - 10 scale ) . Fatigue decreased during the initial 6 weeks by 1.1 in the iron group compared with 0.7 in the placebo group ( P = .07 ) . Efficacy of iron was bound to depleted iron stores : In patients with baseline serum ferritin ≤ 15 ng/mL  , fatigue decreased by 1.8 in the iron group compared with 0.4 in the placebo group ( P = .005 ) , and 82 % of iron-treated compared with 47 % of placebo-treated patients reported improved fatigue ( P = .03 ) . Drug-associated adverse events were observed in 21 % of iron-treated patients and in 7 % of placebo-treated patients ( P = .05 ) ; none of these events was serious . Intravenous administration of  iron improved fatigue in iron-deficient , nonanemic women with a good safety and tolerability profile . The efficacy of intravenous iron was bound to a serum ferritin concentration ≤ 15 ng/mL. This study was registered at the International St and ard R and omized Controlled Trial Number Register ( www.is rct n.org ) as IS RCT N78430425 Background Unexplained fatigue is often left untreated or treated with antidepressants . This r and omized , 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 . Methods Fatigued 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 Switzerl and , blinded to the study drug and r and omized ( computer-generated r and omization 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 ) . Results The 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 . Conclusion A 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 can not 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 Clinical Trials.gov Background : Secondary thrombocytosis is a common clinical feature . In patients with cancer , it is a risk factor for venous thromboembolic events . In inflammatory bowel disease ( IBD ) , thrombocytosis is so far considered a marker of active disease and may contribute to the increased thromboembolic risk in this population . Observed effects of iron therapy on normalization of platelet counts led us to hypothesize that iron itself may regulate megakaryopoiesis . Here , we want to test the effect of iron replacement on platelet count and activity in IBD-associated thrombocytosis . Methods : We performed a r and omized , single-blinded placebo-controlled trial testing the effect of ferric carboxymaltose ( FCM ) in patients with IBD with secondary thrombocytosis ( platelets > 450 G/L ) . Changes in platelet counts , hemoglobin , iron parameters , disease activity , megakaryopoietic growth factors , erythropoietin , and platelet activity were assessed . Patients received placebo or up to 1500 mg iron as FCM . Endpoints were evaluated at week 6 . Results : A total of 26 patients were included in the study , 15 patients were available for the per protocol analysis . A drop in platelets > 25 % ( primary endpoint ) was observed in 4 of 8 ( 50 % , iron group ) and 1 of 7 patients ( 14 % , placebo group , P = 0.143 ) . Mean platelet counts dropped on FCM but not on placebo ( 536 G/L to 411 G/L versus 580 G/L to 559 G/L ; P = 0.002 ) . Disease activity and megakaryopoietic growth factors remained unchanged and hemoglobin and iron parameters increased on FCM . The normalization of platelet counts was associated with a decrease in platelet aggregation and P-selectin expression . Conclusion : FCM lowers platelet counts and platelet activation in patients with IBD-associated secondary thrombocytosis Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed Abstract Objective : Iron deficiency is a common but treatable comorbidity in chronic heart failure ( CHF ) that is associated with impaired health-related quality -of-life ( HRQoL ) . This study evaluates the cost-effectiveness of the intravenous iron preparation ferric carboxymaltose ( FCM ) for the treatment of iron deficiency in CHF from a Swedish healthcare perspective . Methods : A cost-effectiveness analysis with a time horizon of 24 weeks was performed to compare FCM treatment with placebo . Data on health outcomes and medical re source use were mainly taken from the FAIR-HF trial and combined with Swedish cost data . An incremental cost-effectiveness ratio ( ICER ) was calculated as well as the change in per-patient costs for primary care and hospital care . Results : In the FCM group compared with placebo  , quality -adjusted life years ( QALYs ) are higher ( difference = 0.037 QALYs ) , but so are per-patient costs [ ( difference = SEK 2789 ( € 303 ) ] . Primary care and hospital care equally share the additional costs , but within hospitals there is a major shift of costs from inpatient care to outpatient care . The ICER is SEK 75,389 ( € 8194 ) per QALY . The robustness of the result is supported by sensitivity analyses . Conclusions : Treatment of iron deficiency in CHF with FCM compared with placebo is estimated to be cost-effective . The ICER in the base case scenario is twice as high as previously thought , but noticeably below SEK 500,000 ( € 54,300 ) per QALY , an informal average reference value used by the Swedish Dental and Pharmaceutical Benefits Agency . Increased HRQoL and fewer hospitalizations are the key drivers of this result OBJECTIVE The aim of this study was to ascertain whether high-dose intravenous ( IV ) iron sucrose could improve symptoms and change brain iron concentrations in idiopathic RLS . METHODS The study was a r and omized , parallel-group double-blind study of 1000 mg iron sucrose given IV versus placebo . Primary measures of the clinical status were global rating scale ( GRS ) and periodic leg movements of sleep ( PLMS ) . Primary measures of brain iron status were CSF ferritin and MRI-determined iron in the substantia nigra . RESULTS At the time of the interim analysis there were 7 placebo and 11 iron-treated subjects . At 2-weeks post-treatment , iron treatment result ed in a small but significant increase in CSF ferritin and a decrease in RLS severity ( GRS ) but did not change PLMS or MRI iron index . None of the secondary outcomes changed with treatment . There was no single case of clear treatment benefit in any of the patients . This interim analysis revealed an effect size that was too small to allow for adequate power to find significant differences with the planed 36-subject enrollment for either the primary objective outcome of PLMS or any of the secondary outcomes . The study was stopped at this planned break-point given the lack of both adequate power and any indication for clinical ly significant benefit . CONCLUSIONS High-dose IV iron failed to demonstrate the robust changes reported in three prior open-label studies . Differences in iron formulation , dosing regiment , and peripheral iron status may explain some of the discrepancies between this and previous IV iron treatment studies There is limited safety information about ferric carboxymaltose ( FCM ) , a new intravenous iron preparation . This r and omized , crossover study compared the safety and tolerability of double‐blinded intravenous doses of FCM or placebo in patients with iron deficiency anemia . Subjects ( 559 ) with iron deficiency anemia received a dose of either FCM ( 15 mg/kg , maximum 1000 mg ) over 15 minutes or placebo on day 0 . On day 7 , subjects received the other agent . Safety evaluations were performed on days 7 and 14 . The primary endpoint was the incidence of treatment‐emergent adverse events during each 7‐day study period . During the first 24 hours and during the 7‐day treatment period , at least one treatment‐emergent adverse event was experienced by 15.0 % and 29.3 % of subjects after FCM and 11.4 % and 19.7 % after placebo , respectively . Most were classified as Grade 1 or 2 . Six subjects had Grade 3 treatment‐emergent adverse events  after FCM and 9 subjects after placebo . One subject had a Grade 4 , and 1 subject had a Grade 5 treatment‐emergent adverse event , but neither was considered study drug‐related . During the first 24 hours of the treatment period , drug‐related adverse events were reported in 9.3 % of subjects receiving FCM and 4.8 % receiving placebo . Of drug‐related Grade 3 events , 4 subjects received FCM and 5 subjects received placebo . Administration of FCM ( 15 mg/kg , maximum of 1000 mg ) over 15 minutes was well tolerated and associated with minimal risk of adverse reactions in patients with iron deficiency anemia OBJECTIVES To compare the safety and efficacy of iron carboxymaltose with ferrous sulfate to treat iron deficiency anemia in the post partum . METHODS Patients were r and omized ( 2:1 ratio ) to receive iron carboxymaltose  ( up to 3 weekly doses of 1000 mg maximum , applied in 15 min ; n=227 ) or ferrous sulfate ( 100 mg twice daily , 12 weeks ; n=117 ) . Changes in hemoglobin and iron stores up to week 12 were analyzed . RESULTS Iron carboxymaltose was as effective as oral iron sulfate in changing hemoglobin , despite the much shorter treatment period ( 2 weeks vs 12 weeks ) . Ferritin levels were significantly higher . Except for injection site burning , iron carboxymaltose was better tolerated than ferrous sulfate , mainly concerning gastrointestinal side effects . There were no safety concerns identified in breast-fed infants . CONCLUSION Parenteral iron carboxymaltose is a safe and effective treatment option for postpartum anemia , with advantages of a shorter treatment period , better compliance , rapid normalization of iron storages , and lower incidence of gastrointestinal side effects BACKGROUND AIMS : Anemia is a common complication of inflammatory bowel diseases ( IBD ) This multicenter study tested the noninferiority and safety of a new intravenous iron preparation , ferric carboxymaltose ( FeCarb ) , in comparison with oral ferrous sulfate ( FeSulf ) in reducing iron deficiency anemia ( IDA ) in IBD . METHODS : Two hundred patients were r and omized in a 2:1 ratio ( 137 FeCarb:63 FeSulf ) to receive FeCarb ( maximum 1,000 mg iron per infusion ) at 1-wk intervals until the patients ' calculated total iron deficit was reached or FeSulf ( 100 mg b.i.d . ) for 12 wk . The primary end point was change in hemoglobin ( Hb ) from baseline to week 12 . RESULTS : The median Hb improved from 8.7 to 12.3 g/dL in the FeCarb group and from 9.1 to 12.1 g/dL in the FeSulf group , demonstrating noninferiority ( P = 0.6967 ) . Response ( defined as Hb increase of > 2.0 g/dL ) was higher for FeCarb at week 2 ( P = 0.0051 ) and week 4 ( P = 0.0346 ) . Median ferritin increased from 5.0 to 323.5 μg/L at week 2 , followed by a continuous decrease in the FeCarb group ( 43.5 μg/L at week 12 ) . In the FeSulf group , a moderate increase from 6.5 to 28.5 μg/L at week 12 was observed . Treatment-related adverse events ( AEs ) occurred in 28.5 % of the FeCarb and 22.2 % of the FeSulf groups , with discontinuation of study medication due to AEs in 1.5 % and 7.9 % , respectively . CONCLUSIONS : FeCarb is effective and safe in  IBD-associated anemia  . It is noninferior to FeSulf in terms of Hb change over 12 wk , and provides a fast Hb increase and a sufficient refill of iron stores BACKGROUND & AIMS Iron-deficiency anemia is the most common systemic complication of inflammatory bowel diseases ( IBD ) . Iron-deficiency anemia recurs frequently and rapidly after iron-replacement therapy in patients with IBD . We performed a r and omized , placebo-controlled trial to determine if administration of ferric carboxymaltose ( FCM ) prevents anemia in patients with IBD and low levels of serum ferritin . METHODS We performed a single-blind , multicenter study of nonanemic patients who had completed the FERGIcor study .  Serum levels of ferritin were assessed every second month , and patients were given FCM ( total iron dose , 1181 ± 662 mg ; n = 105 ) or placebo ( n = 99 ) when levels decreased to less than 100 μg/L. The primary end point was time to recurrence of anemia within 8 months . Secondary end points included changes of quality of life , disease activity , results from laboratory tests , and adverse events . RESULTS Anemia recurred in 26.7 % of subjects given FCM and in 39.4 % given placebo . The time to anemia recurrence was longer in the FCM group ( hazard ratio , 0.62 ; 95 % confidence interval , 0.38 - 1.00 ; P = .049 ) . Markers of body levels of iron increased or remained at normal levels in subjects given FCM ( ferritin increased by 30.3 μg/L , transferrin saturation increased by 0.6 % ) but decreased in the group given placebo ( ferritin decreased by 36.1 μg/L , transferrin saturation decreased by 4.0 % ) . Changes in quality of life and disease activity were comparable between groups . Adverse events were reported in 59.0 % of the FCM group and 50.5 % of the placebo group , and serious adverse events were reported in 6.7 % and 8.1 % , respectively . CONCLUSIONS FCM prevents recurrence of anemia in patients with IBD , compared with placebo . Nevertheless , the high rate of anemia recurrence warrants optimization of the frequency and requirements for FCM treatment OBJECTIVE : To estimate efficacy of rapid , large-dose intravenous ( IV ) administration of ferric carboxymaltose compared with oral iron therapy in anemic postpartum women . METHODS : In a r and omized , controlled trial , we assigned anemic women ( hemoglobin [ Hb ] less than or equal to 10 g/dL ) within 10 days postpartum to receive either IV ferric carboxymaltose ( less than or equal to1,000 mg over 15 minutes , repeated weekly to achieve a total calculated replacement dose ) or ferrous sulfate ( FeSO4 ) 325 mg orally thrice daily for 6 weeks . RESULTS : One hundred seventy-four patients received 350 IV doses of ferric carboxymaltose ( mean total dose 1,403.1 mg ) in 3 , 2 , or 1 injection ( 10.9 % , 79.3 % , or 9.8 % of patients , respectively ) ; 178 received FeSO4 . Patients assigned to IV ferric carboxymaltose compared with those assigned to oral iron achieved a Hb rise greater than or equal to 2.0 g/dL earlier ( 7.0 compared with 14.0 days , P<.001 ) , were more likely to achieve a Hb rise greater than or equal to 3.0 g/dL at any time ( 86.3 % compared with 60.4 % , P<.001 ) , and were more likely to achieve a Hb greater than 12.0 g/dL ( 90.5 % compared with 68.6 % , P<.001 ) . A similar proportion of patients achieved a Hb rise greater than or equal to 2.0 g/dL ( 96.4 % compared with 94.1 % , IV compared with oral , P=.443 ) . There were no serious adverse drug reactions . CONCLUSION : Large-dose IV ferric carboxymaltose administration is a new iron agent that is effective for the treatment of postpartum anemia . When compared with oral ferrous sulfate , IV ferric carboxymaltose is better tolerated , prompts a more rapid Hb response , and corrects anemia more reliably . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00396292 LEVEL OF EVIDENCE : Background : It is unknown whether intravenous iron or oral iron repletion alone can correct anemia associated with chronic kidney disease ( CKD ) . We conducted a r and omized multicenter controlled trial in adult anemic , iron-deficient non-dialysis CKD ( ND-CKD ) patients ( ≧stage 3 ) not receiving erythropoiesis-stimulating agents ( ESAs ) . Methods : The participants were r and omized to receive either a sodium ferric gluconate complex ( intravenous iron ) 250 mg i.v . weekly × 4 or ferrous sulfate ( oral iron ) 325 mg t.i.d . × 42 days . Hemoglobin ( Hgb ) , ferritin and transferrin saturation ( TSAT ) were measured serially , and the Kidney Disease Quality of Life ( KDQoL ) question naire was administered on days 1 and 43 . The primary outcome variable was change from baseline ( CFB ) to endpoint in Hgb values . Results : Seventy-five patients were analyzed  ( intravenous iron n = 36 , oral iron n = 39 ) . CFB in Hgb was similar in the two groups ( intravenous iron 0.4 g/dl vs. oral iron 0.2 g/dl , p = n.s . ) . However , the increase in Hgb was only significant with intravenous iron ( p < 0.01 ) . In comparison to oral iron , intravenous iron achieved greater improvements in ferritin ( 232.0 ± 160.8 vs. 55.9 ± 236.2 ng/ml , p < 0.001 ) and TSAT ( 8.3 ± 7.5 vs. 2.9 ± 8.8 % , p = 0.007 ) . Intravenous iron caused greater improvements in KDQoL scores than oral iron ( p < 0.05 ) . The most common side effect reported with intravenous iron was hypotension , while constipation was more common with oral iron . Conclusions : Oral and intravenous iron similarly increase Hgb  in anemic iron-depleted ND-CKD patients not receiving ESAs . Although in comparison to oral iron , intravenous iron may result in a more rapid repletion of iron stores and greater improvement in quality of life , it exposes the patients to a greater risk of adverse effects and increases inconvenience and cost OBJECTIVE The objective of the study was to evaluate the efficacy , safety , and tolerability of intravenous ferric carboxymaltose , compared with oral ferrous sulfate in women with postpartum anemia . STUDY DESIGN In a multicenter , r and omized , controlled study , 291 women less than 10 days after delivery with hemoglobin 10 g/dL or less were r and omized to receive ferric carboxymaltose ( n = 143 ) 1000 mg or less intravenously over 15 minutes or less , repeated weekly to a calculated replacement dose ( maximum 2500 mg ) or ferrous sulfate ( n = 148 ) 325 mg orally thrice daily for 6 weeks . RESULTS Ferric carboxymaltose-treated subjects were significantly more likely to : ( 1 ) achieve a hemoglobin greater than 12 g/dL in a shorter time period with a sustained hemoglobin greater than 12 g/dL at day 42 , ( 2 ) achieve hemoglobin rise 3 g/dL or greater more quickly , and ( 3 ) attain higher serum transferrin saturation and ferritin levels . Drug-related adverse events occurred less frequently with ferric carboxymaltose . CONCLUSION Intravenous ferric carboxymaltose was safe and well tolerated with an efficacy superior to oral ferrous sulfate in the treatment of postpartum iron deficiency anemia BACKGROUND The objective was to evaluate efficacy and safety of rapid , large-dose intravenous ( IV ) administration of ferric carboxymaltose compared to oral iron in correcting iron deficiency anemia due to heavy uterine bleeding . STUDY DESIGN AND METHODS In a r and omized , controlled trial , 477 women with anemia , iron deficiency , and heavy uterine bleeding were assigned to receive either IV ferric carboxymaltose ( < or=1000 mg over 15 min , repeated weekly to achieve a total calculated replacement dose ) or 325 mg of ferrous sulfate ( 65 mg elemental iron ) prescribed orally thrice daily for 6 weeks . RESULTS Compared to those assigned to ferrous sulfate , more patients assigned to ferric carboxymaltose responded with a hemoglobin ( Hb ) increase of 2.0 g/dL or more ( 82 % vs. 62 % , 95 % confidence interval for treatment difference 12.2 - 28.3 , p < 0.001 ) , more achieved a 3.0 g/dL or more increase ( 53 % vs. 36 % , p < 0.001 ) , and more achieved correction ( Hb > or= 12 g/dL ) of anemia ( 73 % vs. 50 % , p < 0.001 ) . Patients treated with ferric carboxymaltose compared to those prescribed ferrous sulfate reported greater gains in vitality and physical function and experienced greater improvement in symptoms of fatigue ( p < 0.05 ) . There were no serious adverse drug events . CONCLUSIONS In patients with iron deficiency anemia due to heavy uterine bleeding , rapid IV administration of large doses of a new iron agent , ferric carboxymaltose , is more effective than oral iron therapy in correcting anemia , replenishing iron stores , and improving quality of life OBJECTIVES Our objective was to evaluate in a double-blind , r and omized , placebo-controlled study possible modifications in NT-pro-brain natriuretic peptide ( NT-proBNP ) and C-reactive protein ( CRP ) levels together with clinical and functional parameters , in a group of anemic patients with chronic heart failure ( CHF ) and chronic renal failure ( CRF ) receiving intravenous iron therapy , without recombinant human erythropoietin ( rhEPO ) , versus placebo . BACKGROUND Chronic heart failure and CRF associated with absolute or relative iron deficiency anemia is a common problem . This situation is linked with a variable inflammatory status . Both NT-proBNP and CRP are recognized markers for left ventricular dysfunction and inflammatory status , respectively . In this double-blind , r and omized , placebo-controlled study , modifications in NT-proBNP and CRP level and clinical and functional parameters , in anemic patients with CHF and CRF receiving intravenous iron therapy , without rhEPO , versus placebo were evaluated . METHODS Forty patients with hemoglobin ( Hb ) < 12.5 g/dl , transferrin saturation < 20 % , ferritin < 100 ng/ml , creatinine clearance ( CrCl ) < 90 ml/min , and left ventricular ejection fraction ( LVEF ) < or = 35 % were r and omized into 2 groups ( n = 20 for each ) . For 5 weeks , group A received isotonic saline solution and group B received iron sucrose complex , 200 mg weekly . Minnesota Living with Heart Failure Question naire ( MLHFQ ) and 6-min walk ( 6MW ) test were performed . NT-pro brain natriuretic peptide and CRP were evaluated throughout the study . No patients received erythroprotein any time . RESULTS After 6 months follow-up , group B showed better hematology values and CrCl ( p < 0.01 ) and lower NT-proBNP ( 117.5 + /- 87.4 pg/ml vs. 450.9 + /- 248.8 pg/ml , p < 0.01 ) and CRP ( 2.3 + /- 0.8 mg/l vs. 6.5 + /- 3.7 mg/l , p < 0.01 ) . There was a correlation initially ( p < 0.01 ) between Hb and NT-proBNP ( group A : r = -0.94 and group B : r = -0.81 ) and after 6 months only in group A : r = -0.80 . Similar correlations were observed with Hb and CRP . Left ventricular ejection fraction percentage ( 35.7 + /- 4.7 vs. 28.8 + /- 2.4 ) , MLHFQ score , and 6MW test were all improved in group B ( p < 0.01 ) . Additionally , group B had fewer hospitalizations : 0 of 20 versus group A , 5 of 20 ( p < 0.01 ; relative risk = 2.33 ) . CONCLUSIONS Intravenous iron therapy without rhEPO substantially reduced NT-proBNP and inflammatory status in anemic patients with CHF and moderate CRF . This situation was associated with an improvement in LVEF , NYHA functional class , exercise capacity , renal function , and better quality of life BACKGROUND & AIMS Iron deficiency anemia ( IDA ) is common in chronic diseases and intravenous iron is an effective and recommended treatment . However , dose calculations and inconvenient administration may affect compliance and efficacy . We compared the efficacy and safety of a novel fixed-dose ferric carboxymaltose regimen ( FCM ) with individually calculated iron sucrose ( IS ) doses in patients with inflammatory bowel disease ( IBD ) and IDA . METHODS This r and omized , controlled , open-label , multicenter study included 485 patients with IDA ( ferritin < 100 μg/L , hemoglobin [ Hb ] 7 - 12 g/dL [ female ] or 7 - 13 g/dL [ male ] ) and mild-to-moderate or quiescent IBD at 88 hospitals and clinics in 14 countries . Patients received either FCM in a maximum of 3 infusions of 1000 or 500 mg iron , or Ganzoni-calculated IS dosages in up to 11 infusions of 200 mg iron . Primary end point was Hb response ( Hb increase ≥ 2 g/dL ) ; secondary end points included anemia resolution and iron status normalization by week 12 . RESULTS The results of 240  FCM-treated and 235 IS-treated patients were analyzed . More patients with FCM than IS achieved Hb response ( 150 [ 65.8 % ] vs 118 [ 53.6 % ] ; 12.2 % difference , P = .004 ) or Hb normalization ( 166 [ 72.8 % ] vs 136 [ 61.8 % ] ; 11.0 % difference , P = .015 ) . Both treatments improved quality of life scores by week 12 . Study drugs were well tolerated and drug-related adverse events were in line with drug-specific clinical experience . Deviations from scheduled total iron dosages were more frequent in the IS group . CONCLUSIONS The simpler FCM-based dosing regimen showed better efficacy and compliance , as well as a good safety profile , compared with the Ganzoni-calculated IS dose regimen OBJECTIVES There is evidence of iron deficiency ( ID ) in patients treated with lipoprotein apheresis .  Aim of this study was to assess ID in apheresis patients and to study its management comparing safety and efficacy of two approved intravenous ( i.v . ) iron formulations . METHODS Inclusion criteria were defined as a ) serum ferritin < 300 μg/l and transferrin saturation < 20 % , b ) ferritin < 100 μg/l . Both iron deficient alone and ID anemic ( IDA ) patients were included . Other causes for anemia were ruled out by thorough history-taking and examination/blood tests . Patients were treated with six different lipoprotein apheresis methods : DALI , Liposorber D , TheraSorb LDL , HELP , MONET and Lipidfiltration .  50 patients were r and omized to either ferric carboxymaltose ( FCM , 500 - 1000 mg as single shot infusion over 20 min ) or ferric gluconate ( FG , 62.5 mg once weekly ) . RESULTS 50 of 67 patients of our Lipoprotein Apheresis Center showed iron deficiency . Both i.v . iron formulations studied were equally safe ( no serious adverse events ( SAEs ) , 6 patients /group showed adverse events ( AEs ) ) and both effective ( clinical ly and with respect to laboratory data ) in lipoprotein apheresis patients , however FCM led to a more rapid and steeper rise of iron parameters . CONCLUSIONS ID and IDA are common findings in lipoprotein apheresis patients . The pathogenesis remains yet poorly understood and is probably multifactorial . Differential diagnosis of ID/IDA is as essential as differential therapy . H and led with care , older i.v . iron preparations like FG appear to be safe and effective in lipoprotein apheresis patients . However , novel formulations like FCM can be administered rapidly at higher doses due to high complex stability , allowing faster filling of iron stores . Newer laboratory parameters ( Reticulocyte-He , low/medium/high fluorescence reticulocytes ( LFR/MFR/HFR ) ) assessing iron status may be helpful in early detection of ID and in monitoring iron replacement therapy Levels of hepcidin , a major regulator of iron homeostasis , may identify patients with iron deficiency anemia ( IDA ) who will not respond to oral iron therapy . In this study , IDA patients underwent a 14‐day trial ( run‐in ) course of ferrous sulfate therapy . Nonresponders ( Hgb increase < 1 g/dL with 67 % compliance rate ) were r and omized to IV ferric carboxymaltose ( FCM ; two injections of 750 mg ) or further oral iron for 14 days . Screening hepcidin levels were 38.4 versus 11.3 ng/mL , P = 0.0002 in nonresponders versus responders to a trial of oral iron . Hepcidin of > 20 ng/mL , showed sensitivity of 41.3 % , specificity of 84.4 % , and positive predictive value of 81.6 % for predicting nonresponsiveness to oral iron . PPVs for ferritin > 30 ng/mL or transferrin saturation (TSAT)>15 % were 59.2 and 55 % , respectively . Negative predictive values for hepcidin , ferritin , and TSAT were 46.3 , 22.7 , and 19.7 , respectively . FCM versus oral iron showed Hgb increases of ≥1 gm/dL in 65.3 % versus 20.8 % ( P < 0.0001 ) and Hgb increases of 1.7 ± 1.3 versus 0.6 ± 0.9 g/dL ( P = 0.0025 ) , respectively . We conclude that hepcidin predicts nonresponsiveness to oral iron in patients with IDA and is superior to TSAT or ferritin for this purpose . Nonresponse  to oral iron therapy does not rule out IDA , since two‐thirds of patients subsequently responded to intravenous iron . Am . J. Hematol . 88:97–101 , 2013 . © 2012 Wiley Periodicals , BACKGROUND Iron dextran administration is associated with a high incidence of adverse reactions including anaphylaxis and death . Although dextran , rather than iron , is believed to be the cause of these reactions , it is not known whether iron dextran-sensitive patients can be safely administered another form of parenteral iron , sodium ferric gluconate in sucrose ( SFGC ) . METHODS In a 69 center , prospect i ve , double-blind , controlled trial of safety and tolerability of SFGC , the rate of reactions to SFGC and placebo in 144 iron dextran-sensitive patients was compared with 2194 patients who were previously tolerant to iron dextran preparations .  Serum tryptase levels , a marker of mast cell degranulation , also were measured . RESULTS Among 143 iron dextran-sensitive patients exposed to  SFGC  , three ( 2.1 % ) were intolerant . All three had suspected allergic events to SFGC  , including one patient with a serious reaction ( 0.7 % ) . One dextran-sensitive patient ( 0.7 % ) had a suspected allergic reaction after placebo . In contrast , among 2194 iron dextran-tolerant patients , reactions to  SFGC  were significantly less common , with  SFGC intolerance seen in seven patients ( 0.3 % ; P = 0.020 ) , including five ( 0.2 % ) who had suspected allergic events ( P = 0.010 ) , but none who had serious events ( 0.0 % ; P = 0.061 ) . Two iron dextran-tolerant patients ( 0.09 % ) had allergic-like reactions following placebo injections . Two of the three suspected allergic events in the iron dextran-sensitive group were confirmed as mast cell dependent by a 100 % increase in serum tryptase , while there were no confirmed allergic events in the iron dextran-tolerant group . Long-term exposure to SFGC in iron dextran-sensitive patients result ed in intolerance in only one additional patient and no serious adverse events . CONCLUSIONS Patients with a history of iron dextran sensitivity had approximately sevenfold higher rates of reaction to both placebo and SFGC compared to iron dextran tolerant patients . However , logistic regression analysis , performed to account for the higher reaction rate to placebo , suggests that this increased reactivity was not drug-specific nor immunologically mediated , but represented host idiosyncrasy . These results support the conclusions that reactions to SFGC can be attributed to pseudoallergy , and that SFGC is not a true allergen
target: Conclusions All currently available intravenous iron preparations appear to be safe and effective , but ferric carboxymaltose seems to provide a better and quicker correction of haemoglobin and serum ferritin levels in iron-deficient patients
background: Background Iron deficiency is very common in a number of medical conditions .
  Ferric carboxymaltose is a new stable iron preparation that can be administered in single infusions over short periods of time .
  The aim of this study was to conduct a systematic review of r and omised controlled trials ( RCTs ) regarding the efficacy and safety of the novel complex compared with other iron formulations .
  In addition , the feasibility of a network meta- analysis for indirect comparisons was investigated .