Hemoglobin response to ferric citrate in patients with nondialysis-dependent chronic kidney disease and iron deficiency anemia.
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ABSTRACT:
SUBMITTER: Pergola PE
PROVIDER: S-EPMC6001801 | biostudies-literature | 2018 Jun
REPOSITORIES: biostudies-literature
Publications
Hemoglobin response to ferric citrate in patients with nondialysis-dependent chronic kidney disease and iron deficiency anemia.
Pergola Pablo E PE Fishbane Steven S LeWinter Robin D RD Neylan John F JF Uhlig Katrin K Block Geoffrey A GA Chertow Glenn M GM
American journal of hematology 20180330 6
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Project description:Iron deficiency anemia is common and consequential in nondialysis-dependent CKD (NDD-CKD). Efficacy and tolerability of conventional oral iron supplements are mixed; intravenous iron administration associates with finite but important risks. We conducted a randomized double-blind clinical trial in adults with NDD-CKD and iron deficiency anemia to compare the safety and efficacy of oral ferric citrate (n=117) and placebo (n=115). The primary end point was the proportion of patients who achieved a ≥1.0 g/dl increase in hemoglobin at any time during a 16-week randomized period. Patients who completed the 16-week period could also participate in an 8-week open-label extension period. Significantly more patients randomized to ferric citrate achieved the primary end point (61 [52.1%] versus 22 [19.1%] with placebo; P<0.001). All secondary end points reached statistical significance in the ferric citrate group, including the mean relative change in hemoglobin (0.84 g/dl; 95% confidence interval, 0.58 to 1.10 g/dl; P<0.001) and the proportion of patients who achieved a sustained increase in hemoglobin (≥0.75 g/dl over any 4-week period during the randomized trial; 57 [48.7%] versus 17 [14.8%] with placebo; P<0.001). Rates of serious adverse events were similar in the ferric citrate (12.0%) and placebo groups (11.2%). Gastrointestinal disorders were the most common adverse events, with diarrhea reported in 24 (20.5%) and 19 (16.4%) and constipation in 22 (18.8%) and 15 (12.9%) patients treated with ferric citrate and placebo, respectively. Overall, in patients with NDD-CKD, we found oral ferric citrate to be a safe and efficacious treatment for iron deficiency anemia.
| S-EPMC5461803 | biostudies-literature
Project description:Two randomized, placebo-controlled trials conducted in patients with nondialysis-dependent (NDD) chronic kidney disease (CKD), iron deficiency anemia, and normal or elevated serum phosphorus demonstrated that ferric citrate (FC) significantly increased hemoglobin and decreased serum phosphate concentrations. Pooling these trial results could provide a more robust evaluation of the safety and efficacy of FC in this population. We pooled results of a phase 2 (n = 149) and 3 trial (n = 233) of patients randomized and treated for up to 12 and 16 weeks, respectively. The starting dose in both trials was three 1-g (elemental iron 210 mg) tablets/day with food, up to 12 tablets/day. Doses were titrated in the phase 2 and 3 trials to lower serum phosphate concentrations to a target range (0.97-1.13 mmol/L) and to achieve a ≥10-g/L hemoglobin increase, respectively. Safety was assessed in all patients who received ≥1 dose of FC (n = 190) and placebo (n = 188). Treatment-emergent adverse events (AEs) were reported in 143 of 190 (75.3%) FC-treated and 116 of 188 (61.7%) placebo-treated patients; gastrointestinal AEs were the most frequent (94 [49.5%] vs. 52 [27.7%], respectively). Specific events reported in >5% of patients (FC vs. placebo, respectively) included discolored feces (41 [21.6%] vs. 0 [0.0%]), diarrhea (39 [20.5%] vs. 23 [12.2%]), constipation (35 [18.4%] vs. 19 [10.1%]), and nausea (18 [9.5%] vs. 8 [4.3%]). Twenty FC-treated (10.5%) and 21 placebo-treated patients (11.2%) experienced a serious AE. Two patients (1.1%) died in each group. A pooled efficacy assessment demonstrated a consistent hemoglobin rise and modest serum phosphate decline, with few excursions below the normal range. When used for treatment of patients with NDD-CKD, FC contributes to gastrointestinal AEs at higher rates than placebo, while simultaneously correcting two of the principal metabolic manifestations of CKD (iron deficiency anemia and relative hyperphosphatemia).
| S-EPMC5706696 | biostudies-literature
Project description:BackgroundA combination of safety concerns and labeling changes impacted use of erythropoiesis-stimulating agents (ESAs) in renal anemia. Data regarding contemporary utilization in pre-dialysis chronic kidney disease (CKD) are lacking.MethodsElectronic healthcare records and medical claims data of pre-dialysis CKD patients were aggregated from a large US managed care provider (2011-13). ESA use patterns, characteristics, and outcomes of ESA-treated/untreated patients were quantified.ResultsAt baseline, 109/32,308 patients (0.3%) were ESA users. Treated patients were older, had more advanced CKD (58.8% vs 5.4% with stage 4/5 vs 3) and greater prevalence of comorbid diabetes, hypertension, heart failure, and peripheral vascular disease. An additional 266 patients initiated ESA: hemoglobin at initiation was 8-10 g/dL in 193 of these and >10 g/dL in the remainder; 61.7% had stage 4/5 CKD; prevalence of cardiovascular disease was high (50.8% heart failure; 25.2% prior myocardial infarction; 24.1% prior stroke). During follow-up, rates of death and cardiovascular events were higher in baseline ESA users and ESA naives versus non-users.ConclusionsESA use in pre-dialysis CKD patients was exceedingly rare and directed disproportionately to older, sicker patients; these patients had high rates of death and cardiovascular events. These data provide context for contemporary use of ESA in pre-dialysis CKD.
| S-EPMC5996482 | biostudies-literature
Project description:BackgroundAmong patients with nondialysis-dependent chronic kidney disease (NDD-CKD) and iron-deficiency anemia (IDA), ferric citrate increases hemoglobin and iron parameters and reduces serum phosphate and fibroblast growth factor 23 (FGF23), a key phosphate-regulating hormone. We conducted post hoc analyses of a phase 3 trial to explore associations between iron replacement, serum phosphate changes and FGF23 regulation.MethodsWe employed multivariable regression and longitudinal mixed-effects models to identify and confirm, respectively, whether baseline demographic and laboratory variables were associated with ferric citrate-induced changes in serum phosphate or FGF23 concentrations. We employed path analyses to determine whether changes in FGF23 concentrations were mediated via changes in serum phosphate and/or transferrin saturation (TSAT).ResultsWe analyzed a total of 117 and 115 ferric citrate-treated and placebo-treated patients, respectively. At 16 weeks, ferric citrate significantly reduced serum phosphate versus placebo (P = 0.006) only among patients with elevated baseline serum phosphate (≥4.5 mg/dL) and did not reduce serum phosphate among patients with baseline serum phosphate within the population reference range. Ferric citrate reduced intact FGF23 and C-terminal FGF23 partially via changes in TSAT (for C-terminal FGF23) and serum phosphate (for intact FGF23) and partially via unknown/unmeasured mechanisms.ConclusionsFerric citrate reduced serum FGF23 concentrations (partially via effects on serum phosphate and iron balance) and did not reduce serum phosphate among patients with baseline serum phosphate concentrations within the population reference range.
| S-EPMC6603396 | biostudies-literature
Project description:AIMS:To compare the efficacy and safety of intravenous (IV) ferric carboxymaltose (FCM) versus oral iron and other IV iron therapies in patients with iron-deficiency anemia (IDA) resulting from gastrointestinal (GI) disorders. METHODS:A pooled analysis of four prospective, randomized, active-controlled trials in patients with IDA was performed. Efficacy measures included change from baseline in hemoglobin (Hb), ferritin, and transferrin saturation (TSAT) and correlations of baseline Hb, ferritin, and TSAT to change in Hb. The incidence and type of adverse events were evaluated. RESULTS:A total of 191 patients were evaluated. The mean change in Hb from baseline to the maximum value was 0.8 g/dL with oral iron (P?=?0.001 vs. FCM), 2.2 g/dL with FCM, 2.0 g/dL with any IV iron (P?=?0.391 vs. FCM), and 1.9 g/dL with iron sucrose (P?=?0.329 vs. FCM). Patients treated with FCM and iron sucrose had larger increases in Hb. This effect may have been attributed to a lower baseline Hb level. Drug-related adverse events occurred in 11.9, 12, 26.2, and 25% and serious adverse events (SAEs) occurred in 6.9, 4, 9.8, and 12.5% of patients in the FCM, oral iron, other IV iron therapies, and iron sucrose groups, respectively. No SAEs were considered treatment related in the FCM group, compared with two treatment-related SAEs in two patients (6.3%) in the iron sucrose group. CONCLUSIONS:FCM is an effective therapy in patients with IDA who have GI disorders and has a safety profile comparable to that of other IV iron agents.
| S-EPMC6182423 | biostudies-literature
Project description:BackgroundAdministration of ferric pyrophosphate citrate (FPC, Triferic™) via hemodialysate may allow replacement of ongoing uremic and hemodialysis-related iron losses. FPC donates iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration.MethodsTwo identical Phase 3, randomized, placebo-controlled trials (CRUISE 1 and 2) were conducted in 599 iron-replete chronic hemodialysis patients. Patients were dialyzed with dialysate containing 2 µM FPC-iron or standard dialysate (placebo) for up to 48 weeks. Oral or intravenous iron supplementation was prohibited, and doses of erythropoiesis-stimulating agents were held constant. The primary efficacy end point was the change in hemoglobin (Hgb) concentration from baseline to end of treatment (EoT). Secondary end points included reticulocyte hemoglobin content (CHr) and serum ferritin.ResultsIn both trials, Hgb concentration was maintained from baseline to EoT in the FPC group but decreased by 0.4 g/dL in the placebo group (P < 0.001, combined results; 95% confidence interval [CI] 0.2-0.6). Placebo treatment resulted in significantly larger mean decreases from baseline in CHr (-0.9 pg versus -0.4 pg, P < 0.001) and serum ferritin (-133.1 µg/L versus -69.7 µg/L, P < 0.001) than FPC treatment. The proportions of patients with adverse and serious adverse events were similar in both treatment groups.ConclusionsFPC delivered via dialysate during hemodialysis replaces iron losses, maintains Hgb concentrations, does not increase iron stores and exhibits a safety profile similar to placebo. FPC administered by hemodialysis via dialysate represents a paradigm shift in delivering maintenance iron therapy to hemodialysis patients.
| S-EPMC4656038 | biostudies-literature
Project description:Intravenous (IV) iron is the therapy of choice when oral iron is ineffective or poorly tolerated, yet use has been limited by fears of hypersensitivity reactions (HSRs). Newer formulations that bind iron more tightly and release it more slowly have made the risk of serious or severe HSRs very low. One such formulation, ferric derisomaltose, has been approved in the United States for delivery of 1000 mg iron in a single IV infusion. Ferric derisomaltose rapidly repletes iron parameters with low rates of serious or severe HSRs. Single-infusion iron repletion offers convenience, eliminates adherence concerns, and reduces healthcare resource utilization.
| S-EPMC8248147 | biostudies-literature
Project description:Objective. To evaluate safety and efficacy of intravenous ferric carboxymaltose (FCM) versus standard medical care (SMC) for iron-deficiency anemia (IDA) in postpartum women and women with heavy menstrual bleeding. Study Design. This open-label, multicenter study randomized women with IDA (hemoglobin ≤ 11.0 g/dL) to single doses of FCM (15 mg/kg [maximum 1000 mg]) or SMC (this treatment was determined by the investigator and there may have been no treatment). Safety data (primary outcome) were collected for 30 days. Results. Of 2045 subjects enrolled (FCM: n = 1023; SMC: n = 1022), 996 received FCM and 1022 received SMC. At least 1 serious adverse event (AE) was reported by 0.6% and 2.2% of subjects in the FCM and SMC groups, respectively; none were considered treatment related. The difference in serious AEs was primarily due to higher rates of uterine leiomyoma, uterine hemorrhage, and menorrhagia in SMC subjects with heavy menstrual bleeding. Common AEs were generally predictable, with higher rates of infusion site reactions in FCM subjects and gastrointestinal AEs in SMC subjects. Mean hemoglobin increases were greater in the FCM group than the SMC group. Conclusion. FCM was well tolerated and effectively increased mean hemoglobin levels in postpartum women or women with heavy menstrual bleeding and IDA. This trial is registered with ClinicalTrials.gov, NCT00548860.
| S-EPMC5406716 | biostudies-literature
Project description:PurposePerioperative transfusion is reported to be an independent risk factor not only for postoperative complications but also for early recurrence of periampullary carcinoma after pancreaticoduodenectomy (PD). The purpose of this study was to evaluate the safety and efficacy of ferric carboxymaltose (FCM) in reducing the need for perioperative transfusion in iron deficiency anemia patients scheduled for PD.MethodsTwenty-two male patients (hemoglobin [Hb] 7 to <13 g/dL) and 18 female patients (Hb 7 to <12 g/dL) were enrolled in the study group and administered FCM 1-3 weeks before PD. The perioperative transfusion rate was the primary endpoint; morbidity, length of postoperative hospital stay, change in hematological parameters after FCM injection, and adverse effects of FCM were also investigated.ResultsThe perioperative transfusion rate of the study group was 22.5% (9 of 40). Hb level was significantly higher on the day of the operation compared to baseline (P < 0.001). Levels of Hb, transferrin saturation, and ferritin were higher at the follow-up compared to baseline (P = 0.008, P = 0.033, and P < 0.001, respectively).ConclusionsFCM administration was associated with a reduced need for perioperative transfusion and can safely stabilize hematological parameters.
| S-EPMC10409636 | biostudies-literature
Project description:Oral iron preparations are used as first-line treatment for iron deficiency anemia (IDA), but their gastrointestinal side effects prevent patients from appropriate adherence. We recently conducted a randomized, double-blind, phase 3 non-inferiority study to evaluate the efficacy and safety of two dosages of ferric citrate hydrate (FC) compared with sodium ferrous citrate (SF) in patients with IDA. FC at both 500 and 1000 mg/day was non-inferior to SF at 100 mg/day in terms of the change in the hemoglobin concentration at Week 7 from baseline. Logistic regression analysis suggested that the cumulative proportion of patients who achieved the target hemoglobin concentration (≥ 13.0 g/dL in male patients and ≥ 12.0 g/dL in female patients) at Week 7 was highest among those treated with FC at 1000 mg/day, followed by SF at 100 mg/day and FC at 500 mg/day. Both dosages of FC were well tolerated in patients with IDA. The incidences of nausea and vomiting were significantly lower in the FC treatment groups than in the SF group. In conclusion, FC has potential to be an oral iron preparation with sufficient efficacy for the treatment of IDA and a lower risk of nausea and vomiting.
| S-EPMC10917848 | biostudies-literature