Optimal Serum Ferritin Levels for Iron Deficiency Anemia during Oral Iron Therapy (OIT) in Japanese Hemodialysis Patients with Minor Inflammation and Benefit of Intravenous Iron Therapy for OIT-Nonresponders.

Background: We determined optimal serum ferritin for oral iron therapy (OIT) in hemodialysis (HD) patients with iron deficiency anemia (IDA)/minor inflammation, and benefit of intravenous iron therapy (IIT) for OIT-nonresponders. Methods: Inclusion criteria were IDA (Hb <120 g/L, serum ferritin <227.4 pmol/L). Exclusion criteria were inflammation (C-reactive protein (CRP) ≥ 5 mg/L), bleeding, or cancer. IIT was withheld >3 months before the study. ΔHb ≥ 20 g/L above baseline or maintaining target Hb (tHB; 120-130 g/L) was considered responsive. Fifty-one patients received OIT (ferrous fumarate, 50 mg/day) for 3 months; this continued in OIT-responders but was switched to IIT (saccharated ferric oxide, 40 mg/week) in OIT-nonresponders for 4 months. All received continuous erythropoietin receptor activator (CERA). Hb, ferritin, hepcidin-25, and CERA dose were measured. Results: Demographics before OIT were similar between OIT-responders and OIT-nonresponders except low Hb and high triglycerides in OIT-nonresponders. Thirty-nine were OIT-responders with reduced CERA dose. Hb rose with a peak at 5 months. Ferritin and hepcidin-25 continuously increased. Hb positively correlated with ferritin in OIT-responders (r = 0.913, p = 0.03) till 5 months after OIT. The correlation equation estimated optimal ferritin of 30-40 ng/mL using tHb (120-130 g/L). Seven OIT-nonresponders were IIT-responders. Conclusions: Optimal serum ferritin for OIT is 67.4-89.9 pmol/L in HD patients with IDA/minor inflammation. IIT may be a second line of treatment for OIT-nonreponders.

Financial impact of intravenous iron treatments on the management of anaemia inpatients: a 1 year observational study.

Background Intravenous (IV) iron preparations bypass the difficulties (malabsorption and side effects) associated with oral iron for the treatment of iron deficiency anaemia (IDA). Ferric carboxymaltose (FCM) can be administered as a single infusion over short periods of time but is more expensive than iron sucrose (IS) when the patients are hospitalized. Objectives To evaluate the appropriateness of FCM prescriptions and to establish the economic impact of this management (including disease coding) compared to the use of IV IS. Setting This study was conducted for inpatients in all departments (orthopaedic department, gastroenterology department and two units of the internal medicine department) where FCM was widely prescribed. Method We retrospectively identified 224 patients, diagnosed with IDA using laboratory parameters and/or disease coding, who received FCM between January and December 2014. Main outcome measure The primary outcome was the rate of appropriateness of FCM prescriptions and the financial impact compared to IV IS. Results 89 Patients were included. The total additional cost for an inappropriate prescription of IV FCM (68% of cases) was of 6053 €. The total incremental cost of unsuitable disease coding was estimated at 31,688 €. Indications for IV FCM were categorized: intestinal bleeding (31%), malabsorption (17%), intolerance (9%) and refractory to oral iron (7%). The majority of patients (62%) received 1000 mg of FCM per week. The average length of hospital stay was of 10 days. Conclusion The prescription of IV iron was appropriate in most cases but did not necessarily require FCM. The use of IV IS, in many cases, could present a cost-saving option for inpatients with IDA. The lack of an IDA coding generated incremental costs.

A robust and easily reproducible protocol for the determination of size and size distribution of iron sucrose using dynamic light scattering.

Iron sucrose (IS), a nanocolloidal solution used in the treatment of iron deficiency anemia, is currently under investigation for the elucidation of its critical quality attributes. Assessment of IS's size and size distribution has been recently attempted using dynamic light scattering (DLS). However, due to heterogeneous interpretation of DLS data, variable results were retrieved. The aim of this work was to establish a simple and reproducible DLS protocol to unequivocally define the size and size distribution of IS by using size distribution approximation in Number. Underlining the limitations of the commonly used DLS approximations, we identified the drug as being composed of a population of monodisperse nanoparticles of about 7 nm in diameter. The method here described might therefore be useful for the evaluation of quality, safety and efficacy of IS and its follow-on versions.

Metabonomics of d-glucaro-1,4-lactone in preventing diethylnitrosamine-induced liver cancer in rats.

CONTEXT: d-Glucaro-1,4-lactone (1,4-GL) exists in many vegetables and fruits. Metabonomics has not been used to investigate the role of 1,4-GL in preventing liver cancer. OBJECTIVE: The pharmacological effects and metabolite alterations of 1,4-GL on the prevention of diethylnitrosamine (DEN)-induced liver cancer were investigated. MATERIALS AND METHODS: Ten healthy Sprague-Dawley rats served as control and 46 were used to establish rat liver cancer model. 1HNMR-based metabonomics was used to compare the effects of oral 1,4-GL (50 mg/kg) in liver cancer rats (n = 26) after 10 consecutive weeks of intervention. The amino acids in rat serum were quantified by HPLC-UV, and the changes in Fischer's ratio were calculated. RESULTS: The 20-week survival rate of DEN-induced liver cancer rats administered with oral 1,4-GL was increased from 45.0 to 70.0% with reduced carcinogenesis of the liver and significantly lowered serum α-fetoprotein level (14.28 ± 2.89 ng/mL vs. 18.56 ± 4.65 ng/mL, p = 0.012). The serum levels of leucine, valine, 3-hydroxybutyrate, lactate, acetate and glutamine in the DEN + 1,4-GL group returned to normal levels compared with those of the DEN group on week 20. Fischer's ratio in the rat serum of DEN group was 1.62 ± 0.21, which was significantly lower than that in healthy rats (2.3 ± 0.12). However, Fischer's ratio increased to 1.89 ± 0.22 in the DEN + 1,4-GL group. DISCUSSION AND CONCLUSIONS: 1,4-GL exerted positive effects on liver carcinogenesis in rats by pathological examination and metabonomic analysis. Its mechanism may be related to the restoration of amino acid and energy metabolism.

Iron sucrose: assessing the similarity between the originator drug and its intended copies.

Iron sucrose (IS) is a complex nanocolloidal intravenous suspension used in the treatment of iron-deficiency anemia. Follow-on IS products (iron sucrose similars (ISSs)) have obtained marketing authorization by the generic pathway, implying that identical copies of IS may be manufactured. However, recent prospective and retrospective clinical studies showed discrepancies in clinical outcomes, which might be related to differences in physicochemical properties. The aim of this work is to measure and compare the physicochemical properties of IS and three ISSs available in the market using innovative analytical procedures. The comprehensive elucidation of size, size distribution, morphology, and stability of these complex drugs revealed very significant differences between the products. This study serves to provide the basis to define critical quality attributes that may be linked to differences in clinical outcome and thus may contribute to an adequate regulatory approach for IS and its follow-on products.

Parenteral irons versus transfused red blood cells for treatment of anemia during canine experimental bacterial pneumonia.

BACKGROUND: No studies have been performed comparing intravenous (IV) iron with transfused red blood cells (RBCs) for treating anemia during infection. In a previous report, transfused older RBCs increased free iron release and mortality in infected animals when compared to fresher cells. We hypothesized that treating anemia during infection with transfused fresh RBCs, with minimal free iron release, would prove superior to IV iron therapy. STUDY DESIGN AND METHODS: Purpose-bred beagles (n = 42) with experimental Staphylococcus aureus pneumonia rendered anemic were randomized to be transfused RBCs stored for 7 days or one of two IV iron preparations (7 mg/kg), iron sucrose, a widely used preparation, or ferumoxytol, a newer formulation that blunts circulating iron levels. RESULTS: Both irons increased the alveolar-arterial oxygen gradient at 24 to 48 hours (p = 0.02-0.001), worsened shock at 16 hours (p = 0.02-0.003, respectively), and reduced survival (transfusion 56%; iron sucrose 8%, p = 0.01; ferumoxytol 9%, p = 0.04). Compared to fresh RBC transfusion, plasma iron measured by non-transferrin-bound iron levels increased with iron sucrose at 7, 10, 13, 16, 24, and 48 hours (p = 0.04 to p < 0.0001) and ferumoxytol at 7, 24, and 48 hours (p = 0.04 to p = 0.004). No significant differences in cardiac filling pressures or performance, hemoglobin (Hb), or cell-free Hb were observed. CONCLUSIONS: During canine experimental bacterial pneumonia, treatment of mild anemia with IV iron significantly increased free iron levels, shock, lung injury, and mortality compared to transfusion of fresh RBCs. This was true for iron preparations that do or do not blunt circulating free iron level elevations. These findings suggest that treatment of anemia with IV iron during infection should be undertaken with caution.

The Ferumoxytol for Anemia of CKD Trial (FACT)-a randomized controlled trial of repeated doses of ferumoxytol or iron sucrose in patients on hemodialysis: background and rationale.

BACKGROUND: Iron deficiency anemia (IDA) is a common manifestation of chronic kidney disease (CKD), affecting most patients on hemodialysis and imposing a substantial clinical burden. Treatment with iron supplementation increases hemoglobin levels and can reduce the severity of anemia in patients with CKD. While correcting anemia in these patients is an important therapeutic goal, there is a lack of long-term trials directly comparing intravenous iron therapies in patients with CKD receiving hemodialysis. METHODS/DESIGN: The Ferumoxytol for Anemia of CKD Trial (FACT) is a 13-month, open-label, randomized, multicenter, international, prospective study with 2 substudies. Entry criteria for the main study include adults with IDA (defined as hemoglobin <11.5 g/dL [<115.0 g/L] and a transferrin saturation <30%), serum ferritin <800 ng/mL (<1798 pmol/L), and receiving hemodialysis for ≥3 months. Patients are randomized to receive ferumoxytol (1.02 g over 2 doses) or iron sucrose (1.0 g over 10 doses) during the initial 5-week treatment period. Those with persistent/recurrent IDA over the 11-month observation period will receive additional 5-week treatment periods, as appropriate. The primary efficacy endpoint of the main study is the mean change in hemoglobin from Baseline to Week 5 for each treatment period. The secondary efficacy endpoints include the mean change in transferrin saturation from Baseline to Week 5 and the proportion of patients with a hemoglobin increase of ≥1.0 g/dL at any time from Baseline to Week 5. Safety will be assessed through an examination of the adverse event profile over the course of the study. An "oxidative stress" substudy in approximately 100 patients will assess the effects of treatment on biomarkers of oxidative stress/inflammation during the initial 5-week treatment period, and a magnetic resonance imaging substudy in approximately 70 patients will assess the potential for iron deposition in target tissues over 24 months. DISCUSSION: FACT fulfills the need for a long-term comparative trial in patients with IDA and CKD receiving hemodialysis. The efficacy and safety results will provide useful information for guiding therapy in this population. Two hundred ninety-six patients have been enrolled, and completion of the main study is expected soon. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01227616 (registered October 22, 2010); EudraCT number: 2010-022133-28.

Safety of Intravenous Iron in Hemodialysis: Longer-term Comparisons of Iron Sucrose Versus Sodium Ferric Gluconate Complex.

BACKGROUND: Controversy exists about any differences in longer-term safety across different intravenous iron formulations routinely used in hemodialysis (HD) patients. We exploited a natural experiment to compare outcomes of patients initiating HD therapy in facilities that predominantly (in ≥90% of their patients) used iron sucrose versus sodium ferric gluconate complex. STUDY DESIGN: Retrospective cohort study of incident HD patients. SETTING & PARTICIPANTS: Using the US Renal Data System, we hard-matched on geographic region and center characteristics HD facilities predominantly using ferric gluconate with similar ones using iron sucrose. Subsequently, incident HD patients were assigned to their facility iron formulation exposure. INTERVENTION: Facility-level use of iron sucrose versus ferric gluconate. OUTCOMES: Patients were followed up for mortality from any, cardiovascular, or infectious causes. Medicare-insured patients were followed up for infectious and cardiovascular (stroke or myocardial infarction) hospitalizations and for composite outcomes with the corresponding cause-specific deaths. MEASUREMENTS: HRs. RESULTS: We matched 2,015 iron sucrose facilities with 2,015 ferric gluconate facilities, in which 51,603 patients (iron sucrose, 24,911; ferric gluconate, 26,692) subsequently initiated HD therapy. All recorded patient characteristics were balanced between groups. Over 49,989 person-years, 10,381 deaths (3,908 cardiovascular and 1,209 infectious) occurred. Adjusted all-cause (HR, 0.98; 95% CI, 0.93-1.03), cardiovascular (HR, 0.96; 95% CI, 0.89-1.03), and infectious mortality (HR, 0.98; 95% CI, 0.86-1.13) did not differ between iron sucrose and ferric gluconate facilities. Among Medicare beneficiaries, no differences between ferric gluconate and iron sucrose facilities were observed in fatal or nonfatal cardiovascular events (HR, 1.01; 95% CI, 0.93-1.09). The composite infectious end point occurred less frequently in iron sucrose versus ferric gluconate facilities (HR, 0.92; 95% CI, 0.88-0.96). LIMITATIONS: Unobserved selection bias from nonrandom treatment assignment. CONCLUSIONS: Patients initiating HD therapy in facilities almost exclusively using iron sucrose versus ferric gluconate had similar longer-term outcomes. However, there was a small decrease in infectious hospitalizations and deaths in patients dialyzing in facilities predominantly using iron sucrose. This difference may be due to residual confounding, random chance, or a causal effect.

Distinct in vitro Complement Activation by Various Intravenous Iron Preparations.

BACKGROUND: Intravenous (IV) iron preparations are widely used in the treatment of anemia in patients undergoing hemodialysis (HD). All IV iron preparations carry a risk of causing hypersensitivity reactions. However, the pathophysiological mechanism is poorly understood. We hypothesize that a relevant number of these reactions are mediated by complement activation, resulting in a pseudo-anaphylactic clinical picture known as complement activation-related pseudo allergy (CARPA). METHODS: First, the in-vitro complement-activating capacity was determined for 5 commonly used IV iron preparations using functional complement assays for the 3 pathways. Additionally, the preparations were tested in an ex-vivo model using the whole blood of healthy volunteers and HD patients. Lastly, in-vivo complement activation was tested for one preparation in HD patients. RESULTS: In the in-vitro assays, iron dextran, and ferric carboxymaltose caused complement activation, which was only possible under alternative pathway conditions. Iron sucrose may interact with complement proteins, but did not activate complement in-vitro. In the ex-vivo assay, iron dextran significantly induced complement activation in the blood of healthy volunteers and HD patients. Furthermore, in the ex-vivo assay, ferric carboxymaltose and iron sucrose only caused significant complement activation in the blood of HD patients. No in-vitro or ex-vivo complement activation was found for ferumoxytol and iron isomaltoside. IV iron therapy with ferric carboxymaltose in HD patients did not lead to significant in-vivo complement activation. CONCLUSION: This study provides evidence that iron dextran and ferric carboxymaltose have complement-activating capacities in-vitro, and hypersensitivity reactions to these drugs could be CARPA-mediated.

Is there any role of intravenous iron for the treatment of anemia in cancer?

BACKGROUND: Anemia is a major cause of morbidity in patients with cancer resulting in poor physical performance, prognosis and therapy outcome. The aim of this study is to assess the efficacy of intravenous (iv) iron administration for the correction of anemia, for the prevention of exacerbation of anemia, for decreasing blood transfusion rates, and for the survival of cancer patients. METHODS: Patients with different solid tumor diagnosis who received iv iron during their cancer treatment were evaluated retrospectively. Sixty-three patients with hemoglobin (Hgb) levels between ≥ 9 g/dL, and ≤ 10 g/dL, and no urgent need for red blood cell transfusion were included in this retrospective analysis. The aim of cancer treatment was palliative for metastatic patients (36 out of 63), or adjuvant or curative for patients with localized disease (27 out of 63). All the patients received 100 mg of iron sucrose which was delivered intravenously in 100 mL of saline solution, infused within 30 min, 5 infusions every other day. Complete blood count, serum iron, and ferritin levels before and at every 1 to 3 months subsequently after iv iron administration were followed regularly. RESULTS: Initial mean serum Hgb, serum ferritin and serum iron levels were 9.33 g/dL, 156 ng/mL, and 35.9 µg/dL respectively. Mean Hgb, ferritin, and iron levels 1 to 3 months, and 6 to 12 months after iv iron administration were 10.4 g/dL, 11.2 g/dL, 298.6 ng/mL, 296.7 ng/mL, and 71.6 µg/dL, 67.7 µg/dL respectively with a statistically significant increase in the levels (p < 0.001). Nineteen patients (30 %) however had further decrease in Hgb levels despite iv iron administration, and blood transfusion was necessary in 18 of these 19 patients (28.5 %). The 1-year overall survival rates differed in metastatic cancer patients depending on their response to iv iron; 61.1 % in responders versus 35.3 % in non-responders, (p = 0.005), furthermore response to iv iron correlated with tumor response to cancer treatment, and this relation was statistically significant, (p < 0.001). CONCLUSIONS: Iv iron administration in cancer patients undergoing active oncologic treatment is an effective and safe measure for correction of anemia, and prevention of worsening of anemia. Amelioration of anemia and increase in Hgb levels with iv iron administration in patients with disseminated cancer is associated with increased tumor response to oncologic treatment and overall survival. Response to iv iron may be both a prognostic and a predictive factor for response to cancer treatment and survival.

Combined iron sucrose and protoporphyrin treatment protects against ischemic and toxin-mediated acute renal failure.

Tissue preconditioning, whereby various short-term stressors initiate organ resistance to subsequent injury, is well recognized. However, clinical preconditioning of the kidney for protection against acute kidney injury (AKI) has not been established. Here we tested whether a pro-oxidant agent, iron sucrose, combined with a protoporphyrin (Sn protoporphyrin), can induce preconditioning and protect against acute renal failure. Mice were pretreated with iron sucrose, protoporphyrin, cyanocobalamin, iron sucrose and protoporphyrin, or iron sucrose and cyanocobalamin. Eighteen hours later, ischemic, maleate, or glycerol models of AKI were induced, and its severity was assessed the following day (blood urea nitrogen, plasma creatinine concentrations; post-ischemic histology). Agent impact on cytoprotective gene expression (heme oxygenase 1, hepcidin, haptoglobin, hemopexin, α1-antitrypsin, α1-microglobulin, IL-10) was assessed as renal mRNA and protein levels. AKI-associated myocardial injury was gauged by plasma troponin I levels. Combination agent administration upregulated multiple cytoprotective genes and, unlike single agent administration, conferred marked protection against each tested model of acute renal failure. Heme oxygenase was shown to be a marked contributor to this cytoprotective effect. Preconditioning also blunted AKI-induced cardiac troponin release. Thus, iron sucrose and protoporphyrin administration can upregulate diverse cytoprotective genes and protect against acute renal failure. Associated cardiac protection implies potential relevance to both AKI and its associated adverse downstream effects.

Iron Treatment Strategies in Dialysis-Dependent CKD.

Iron deficiency is common in patients on chronic dialysis, and most require iron-replacement therapy. In addition to absolute iron deficiency, many patients have functional iron deficiency as shown by a suboptimal response to the use of erythropoietin-stimulating agents. Both absolute and functional iron-deficiency anemia have been shown to respond to intravenous (IV) iron replacement. Although parenteral iron is an efficacious method and superior to standard doses of oral iron in patients on hemodialysis, there are ongoing safety concerns about repeated exposure potentially enhancing infection risk and cardiovascular disease. Each IV iron product is composed of an iron core with a carbohydrate shell. The avidity of iron binding and the type of carbohydrate shell play roles in the safe maximal dose and the frequency and severity of acute infusion reactions. All IV iron products are taken up into the reticuloendothelial system where the shell is metabolized and the iron is stored within tissue ferritin or exported to circulating transferrin. IV iron can be given as large intermittent doses (loading therapy) or in smaller doses at frequent intervals (maintenance dosing regimen). Limited trial data and observational data suggest that a maintenance dosing regimen is more efficacious and possibly safer than loading therapy. There is no consensus regarding the preferred method of iron repletion in patients on peritoneal dialysis, although small studies comparing oral and parenteral iron regimens in these patients have shown the latter to be more efficacious. Use of IV iron in virtually all hemodialysis and many peritoneal dialysis patients remains the standard of care.

Iron Treatment Strategies in Nondialysis CKD.

In contrast to managing patients on hemodialysis in whom iron strategies are more focused on intravenous iron, nondialysis chronic kidney disease (CKD) patients may receive either oral or intravenous iron. There are advantages and disadvantages for both strategies. Oral iron is simple and cheap to administer and does not require hospital visits, but is poorly absorbed in advanced CKD and is associated with unpleasant gastrointestinal side effects. Intravenous iron, on the other hand, guarantees iron bioavailability and avoids problems of variable absorption of iron from the gastrointestinal tract, but requires specialist clinic services. Intravenous iron also is associated with hypersensitivity reactions, albeit very rarely. The efficacy of intravenous iron in improving hemoglobin, ferritin, and transferrin saturation is well established, and superior to oral iron, but the long-term safety of this route of administration has not been established and there are theoretical concerns that patients may be exposed to increased oxidative stress and exacerbation of infections. The final choice of iron management strategy will depend on individual physician preference, as well as the facilities that are available.

Usefulness of Reticulocyte Hemoglobin Equivalent in Management of Regular Hemodialysis Patients with Iron Deficiency Anemia.

INTRODUCTION: Reticulocyte hemoglobin equivalent (RET-He) is a new parameter for evaluating iron status. This study aims to assess diagnostic value and investigate RET-He as early predictor of response to intravenous iron supplementation. METHODS: Seventy-two regular hemodialysis patients at Adam Malik Hospital were studied from April to May 2011. RET-He was compared with conventional iron parameters for identification of iron deficiency. Fifteen patients with iron deficiency anemia were selected to receive 100 mg iron sucrose intravenous during every dialysis session (2x/weeks) for 4 weeks. RESULTS: Receiver operating characteristic (ROC) curve for RET-He revealed the value of area under the curve was 0.818 (p < 0.0001). Using cutoff level 31.65 pg, RET-He showed 81.5% sensitivity and 61.6% specificity. Serum ferritin (r = 0.499, p < 0.0001) and transferrin saturation/ TSAT (r = 0.592, p < 0.0001) were correlated to RET-He. Significant improvement in hemoglobin, hematocrit and RET-He were found after intervention (p = 0.023, p = 0.049 and p = 0.019, respectively). CONCLUSION: RET-He is a useful marker of iron deficiency and early predictor of response to intravenous iron supplementation in regular hemodialysis patients.

Performance of a Predictive Model for Long-Term Hemoglobin Response to Darbepoetin and Iron Administration in a Large Cohort of Hemodialysis Patients.

Anemia management, based on erythropoiesis stimulating agents (ESA) and iron supplementation, has become an increasingly challenging problem in hemodialysis patients. Maintaining hemodialysis patients within narrow hemoglobin targets, preventing cycling outside target, and reducing ESA dosing to prevent adverse outcomes requires considerable attention from caregivers. Anticipation of the long-term response (i.e. at 3 months) to the ESA/iron therapy would be of fundamental importance for planning a successful treatment strategy. To this end, we developed a predictive model designed to support decision-making regarding anemia management in hemodialysis (HD) patients treated in center. An Artificial Neural Network (ANN) algorithm for predicting hemoglobin concentrations three months into the future was developed and evaluated in a retrospective study on a sample population of 1558 HD patients treated with intravenous (IV) darbepoetin alfa, and IV iron (sucrose or gluconate). Model inputs were the last 90 days of patients' medical history and the subsequent 90 days of darbepoetin/iron prescription. Our model was able to predict individual variation of hemoglobin concentration 3 months in the future with a Mean Absolute Error (MAE) of 0.75 g/dL. Error analysis showed a narrow Gaussian distribution centered in 0 g/dL; a root cause analysis identified intercurrent and/or unpredictable events associated with hospitalization, blood transfusion, and laboratory error or misreported hemoglobin values as the main reasons for large discrepancy between predicted versus observed hemoglobin values. Our ANN predictive model offers a simple and reliable tool applicable in daily clinical practice for predicting the long-term response to ESA/iron therapy of HD patients.

Randomized controlled trial comparing ferric carboxymaltose and iron sucrose for treatment of iron deficiency anemia due to abnormal uterine bleeding.

OBJECTIVE: To evaluate the efficacy and safety of intravenous ferric carboxymaltose (FCM) in comparison with intravenous iron sucrose (ISC) in the treatment of anemia due to abnormal uterine bleeding (AUB). METHODS: A randomized controlled trial was conducted between April 2013 and May 2014 in patients older than 18 years of age presenting at a hospital in New Delhi, India, with anemia due to AUB. Patients were randomized in a 1:1 ratio to receive treatment with intravenous FCM or ISC. The primary outcome, increase in hemoglobin above baseline, was monitored over a 12-week period. Patients completing the full treatment and follow-up protocol were included in the analyses. Participants and investigators were not masked to treatment allocations. RESULTS: Overall, 30 patients were assigned to each group. Increases in mean hemoglobin levels from baseline were significantly higher in the FCM group at 6 weeks (P=0.005). At 12 weeks, there was no significant difference in hemoglobin increase from baseline between the two groups (P=0.11). Adverse events were similar between both treatment groups. CONCLUSION: Treatment with FCM resulted in a rapid increase in hemoglobin levels in patients with anemia due to AUB, with similar increases in hemoglobin over a 12-week period. Clinical Trial Registration (www.ctri.nic.in):CTRI/2015/09/006224.

Does IV Iron Induce Plasma Oxidative Stress in Critically Ill Patients? A Comparison With Healthy Volunteers.

OBJECTIVE: To compare the oxidative stress induced by IV iron infusion in critically ill patients and in healthy volunteers. DESIGN: Multicenter, interventional study. SETTING: Two ICUs and one clinical research center. SUBJECTS: Anemic critically ill patients treated with IV iron and healthy volunteers. INTERVENTIONS: IV infusion of 100 mg of iron sucrose. MEASUREMENTS AND MAIN RESULTS: Thirty-eight anemic patients (hemoglobin, median [interquartile range] = 8.4 g/dL [7.7-9.2]) (men, 25 [66%]; aged 68 yr [48-77]; Simplified Acute Physiology Score II, 48.5 [39-59]) and 39 healthy volunteers (men, 18 [46%]; aged 42.1 yr [29-50]) were included. Blood samples were drawn before (H0) and 2, 6, and 24 hours (H2, H6, and H24) after a 60-minute iron infusion for the determination of nontransferrin bound iron, markers of lipid peroxidation-8α-isoprostanes, protein oxidation-advanced oxidized protein product, and glutathione reduced/oxidized. Iron infusion had no effect on hemodynamic parameter in patients and volunteers. At baseline, patients had much higher interleukin-6, C-reactive protein, and hepcidin levels. 8α-isoprostanes was also higher in patients at baseline (8.5 pmol/L [6.5-12.9] vs 4.6 pmol/L [3.5-5.5]), but the area under the curve above baseline from H0 to H6 was not different (p = 0.38). Neither was it for advanced oxidized protein product and nontransferrin bound iron. The area under the curve above baseline from H0 to H6 (glutathione reduced/oxidized) was lower in volunteers (p = 0.009). Eight patients had a second set of dosages (after the fourth iron infusion), showing higher increase in 8α-isoprostanes. CONCLUSIONS: In our observation, IV iron infusion does not induce more nontransferrin bound iron, lipid, or protein oxidation in patients compared with volunteers, despite higher inflammation, oxidative stress, and hepcidin levels and lower antioxidant at baseline. In contrary, iron induces a greater decrease in antioxidant, compatible with higher oxidative stress in volunteers than in critically ill patients.