Primary studies included in this systematic review

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28 articles (28 References) Revert Studify

Primary study

Unclassified

Journal American journal of kidney diseases : the official journal of the National Kidney Foundation
Year 2015
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BACKGROUND: Iron deficiency anemia and serum phosphate levels > 4.0mg/dL are relatively common in chronic kidney disease stages 3 to 5 and are associated with higher risks of progressive loss of kidney function, cardiovascular events, and mortality. STUDY DESIGN: Double-blind, placebo-controlled, randomized trial. SETTING & PARTICIPANTS: 149 patients with estimated glomerular filtration rates < 60 mL/min/1.73 m(2), iron deficiency anemia (hemoglobin, 9.0-12.0 g/dL; transferrin saturation [TSAT]≤ 30%, serum ferritin ≤ 300 ng/mL), and serum phosphate levels ≥ 4.0 to 6.0mg/dL. Use of intravenous iron or erythropoiesis-stimulating agents was prohibited. INTERVENTION: Randomization to treatment for 12 weeks with ferric citrate coordination complex (ferric citrate) or placebo. OUTCOMES & MEASUREMENTS: Coprimary end points were change in TSAT and serum phosphate level from baseline to end of study. Secondary outcomes included change from baseline to end of treatment in values for ferritin, hemoglobin, intact fibroblast growth factor 23 (FGF-23), urinary phosphate excretion, and estimated glomerular filtration rate. RESULTS: Ferric citrate treatment increased mean TSAT from 22% ± 7% (SD) to 32% ± 14% and reduced serum phosphate levels from 4.5 ± 0.6 to 3.9 ± 0.6 mg/dL, while placebo exerted no effect on TSAT (21% ± 8% to 20% ± 8%) and less effect on serum phosphate level (4.7 ± 0.6 to 4.4 ± 0.8 mg/dL; between-group P<0.001 for each). Ferric citrate increased hemoglobin levels (from 10.5 ± 0.8 to 11.0 ± 1.0 g/dL; P<0.001 vs placebo), reduced urinary phosphate excretion 39% (P<0.001 vs placebo), and reduced serum intact FGF-23 levels from a median of 159 (IQR, 102-289) to 105 (IQR, 65-187) pg/mL (P=0.02 vs placebo). The incidence and severity of adverse effects were similar between treatment arms. LIMITATIONS: The study is limited by relatively small sample size and short duration and by having biochemical rather than clinical outcomes. CONCLUSIONS: Short-term use of ferric citrate repletes iron stores, increases hemoglobin levels, and reduces levels of serum phosphate, urinary phosphate excretion, and FGF-23 in patients with chronic kidney disease stages 3 to 5.

Primary study

Unclassified

Authors Lee CT , Wu IW , Chiang SS , Peng YS , Shu KH , Wu MJ , Wu MS
Journal Journal of nephrology
Year 2015
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BACKGROUND: Hyperphosphatemia is a common complication in dialysis patients that can be treated by oral phosphate binders. We investigated the efficacy and safety of oral ferric citrate as a phosphate binder for Taiwanese patients with end stage renal disease and with hyperphosphatemia who were undergoing hemodialysis. METHODS: This was a prospective, double-blind, placebo-controlled, randomized trial carried out in 5 hospitals in Taiwan. Ferric citrate (4 or 6 g/day) or placebo was administered for 56 days. Serum calcium, phosphorous levels, calcium × phosphorus product, serum ferritin level, transferrin saturation, and adverse events were recorded. RESULTS: A total of 166 patients completed the trial. The placebo group had relatively constant serum data. Serum phosphorus declined significantly in the 6 g/day group (p < 0.05 for 4 and 8 weeks) and the 4 g/day group (p < 0.05 for 4 and 8 weeks). There were similar changes in the calcium × phosphorus product. The serum ferritin level increased significantly in the 6 g/day group (p < 0.05) and the 4 g/day group (p < 0.05). There were similar changes in transferrin saturation. Most adverse events were mild to moderate and were comparable among the three groups. CONCLUSIONS: A 56-day treatment with ferric citrate effectively controlled hyperphosphatemia and was well tolerated in maintenance hemodialysis patients. There were also moderate increases in serum ferritin and transferrin saturation.

Primary study

Unclassified

Journal Journal of the American Society of Nephrology : JASN
Year 2015
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Patients on dialysis require phosphorus binders to prevent hyperphosphatemia and are iron deficient. We studied ferric citrate as a phosphorus binder and iron source. In this sequential, randomized trial, 441 subjects on dialysis were randomized to ferric citrate or active control in a 52-week active control period followed by a 4-week placebo control period, in which subjects on ferric citrate who completed the active control period were rerandomized to ferric citrate or placebo. The primary analysis compared the mean change in phosphorus between ferric citrate and placebo during the placebo control period. A sequential gatekeeping strategy controlled study-wise type 1 error for serum ferritin, transferrin saturation, and intravenous iron and erythropoietin-stimulating agent usage as prespecified secondary outcomes in the active control period. Ferric citrate controlled phosphorus compared with placebo, with a mean treatment difference of -2.2±0.2 mg/dl (mean±SEM) (P&lt;0.001). Active control period phosphorus was similar between ferric citrate and active control, with comparable safety profiles. Subjects on ferric citrate achieved higher mean iron parameters (ferritin=899±488 ng/ml [mean±SD]; transferrin saturation=39%±17%) versus subjects on active control (ferritin=628±367 ng/ml [mean±SD]; transferrin saturation=30%±12%; P&lt;0.001 for both). Subjects on ferric citrate received less intravenous elemental iron (median=12.95 mg/wk ferric citrate; 26.88 mg/wk active control; P&lt;0.001) and less erythropoietin-stimulating agent (median epoetin-equivalent units per week: 5306 units/wk ferric citrate; 6951 units/wk active control; P=0.04). Hemoglobin levels were statistically higher on ferric citrate. Thus, ferric citrate is an efficacious and safe phosphate binder that increases iron stores and reduces intravenous iron and erythropoietin-stimulating agent use while maintaining hemoglobin.

Primary study

Unclassified

Journal Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
Year 2014
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BACKGROUND: JTT-751 is a novel phosphate binder containing ferric citrate as the active ingredient. METHODS: In this Phase 3, multicenter, randomized, open-label, parallel-group study, we compared the efficacy and safety of JTT-751 and sevelamer hydrochloride in patients undergoing hemodialysis. A total of 230 patients with a serum phosphate ≥1.97 and <3.23 mmol/L were randomized to JTT-751 (dose adjusted between 1.5 and 6.0 g/day) or sevelamer hydrochloride (dose adjusted between 3.0 and 9.0 g/day) for 12 weeks. The primary outcome was change in serum phosphate from baseline to end of treatment. Secondary outcomes included the changes in corrected serum calcium and intact parathyroid hormone (PTH). The changes in ferritin, transferrin saturation and erythropoiesis-stimulating agent dose were additional outcomes. RESULTS: Changes in serum phosphate at the end of treatment were -0.82 mmol/L in the JTT-751 group and -0.78 mmol/L in the sevelamer group, establishing non-inferiority of JTT-751 compared with sevelamer (least squares mean, -0.03 mmol/L; 95% confidence interval, -0.13 to 0.07 mmol/L). Corrected serum calcium increased and PTH decreased from baseline within both groups; changes between groups were similar. Gastrointestinal disorders were the most common adverse events in both groups; the incidence of diarrhea was higher in the JTT-751 group, while constipation occurred frequently in the sevelamer group. Treatment with JTT-751 resulted in significant relative increases in serum ferritin and transferrin saturation. CONCLUSIONS: Efficacy and safety of JTT-751 was comparable to sevelamer in patients on hemodialysis with hyperphosphatemia. Differential adverse effects were observed; biochemical markers of iron status increased in patients treated with JTT-751. TRIAL REGISTRATION NUMBER: CTI-111433 (The Japan Pharmaceutical Information Center at: http//www.clinicaltrials.jp). Date of registration: 7 March 2011.

Primary study

Unclassified

Journal BMC nephrology
Year 2014
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BACKGROUND: High levels of circulating fibroblast growth factor 23 (FGF23) are associated with chronic kidney disease (CKD) progression and high mortality. In the Phosphate Reduction Evaluation of FGF23 in Early CKD Treatment (PREFECT) study, we assessed the effect of reducing intestinal phosphate absorption using lanthanum carbonate on FGF23 levels in normophosphatemic patients with CKD stage 3. METHODS: Thirty-five individuals were randomized to lanthanum carbonate 3000 mg/day (n=23) or placebo (n=12) for 12 weeks. Levels of intact FGF23 (iFGF23), C-terminal FGF23, serum and urinary phosphate and calcium, intact parathyroid hormone and 1,25-dihydroxyvitamin D were assessed. RESULTS: The median age was 65 years in the lanthanum group and 73 years in the placebo group; 58.8% and 41.7% were men, respectively. No significant difference was seen in mean iFGF23 between groups at week 12. There was, however, a transient reduction from baseline in iFGF23 in the lanthanum group at week 1, from 70.5 pg/ml to 51.9 pg/ml, which was not seen in the placebo group; this between-group difference in percentage change from baseline was significant in post hoc analyses (p=0.0102). Urinary phosphate decreased after 1 week of lanthanum treatment and remained low at week 12. CONCLUSIONS: Reducing intestinal phosphate absorption with lanthanum carbonate did not lead to sustained reductions in iFGF23 in patients with CKD stage 3, although phosphaturia decreased. This suggests that factors other than phosphate burden may be responsible for driving increases in circulating FGF23 in patients with CKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT01128179, 20 May 2010.

Primary study

Unclassified

Journal Clinical nephrology
Year 2014
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BACKGROUND: Lanthanum carbonate (LC), an effective non-calcium phosphate binder is widely used to manage hyperphosphatemia in patients with chronic kidney disease (CKD) on dialysis. Recently, the additional indication for control of hyperphosphatemia in CKD patients not on dialysis has been approved. METHODS: A multicenter, randomized, double-blind, placebo-controlled trial to confirm the efficacy and safety of LC in Japanese hyperphosphatemic stage 4 - 5 CKD patients not on dialysis. After a 4-week run-in period, 143 eligible subjects with serum phosphate levels of 5.6 - 11.0 mg/dL were randomized (2 : 1) to receive LC or placebo (88 vs. 55) for 8 weeks; 119 subjects completed the study (76 vs. 43). The starting LC dose was 750 mg/day, which was then up-titrated to 2,250 mg/day as needed while tolerated. Primary efficacy analysis was performed on the intent-to-treat (ITT) population of 141 patients (86 vs. 55). RESULTS: LC produced a significantly greater reduction in serum phosphate level compared with placebo after 8 weeks of treatment (difference, 0.97 (95% CI: 0.58, 1.37) mg/ dL; p < 0.0001). The cumulative proportion of subjects with controlled phosphate levels ≤ 4.6 mg/dL was higher in the LC group than the placebo group (59.56% vs. 10.46%). LC caused significantly greater reductions in serum Ca × P product and urinary phosphate excretion compared with placebo. The safety profile of LC was similar to that of placebo. CONCLUSIONS: This study demonstrated the effectiveness of LC to control hyperphosphatemia in pre-dialysis CKD patients.

Primary study

Unclassified

Journal Clinical journal of the American Society of Nephrology : CJASN
Year 2014
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BACKGROUND AND OBJECTIVES: Ferric citrate hydrate is a novel iron-based phosphate binder being developed for hyperphosphatemia in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A phase 3, multicenter, randomized, double blind, placebo-controlled study investigated the efficacy and safety of ferric citrate hydrate in nondialysis-dependent patients with CKD. Starting in April of 2011, 90 CKD patients (eGFR=9.21±5.72 ml/min per 1.73 m(2)) with a serum phosphate≥5.0 mg/dl were randomized 2:1 to ferric citrate hydrate or placebo for 12 weeks. The primary end point was change in serum phosphate from baseline to the end of treatment. Secondary end points included the percentage of patients achieving target serum phosphate levels (2.5-4.5 mg/dl) and change in fibroblast growth factor-23 at the end of treatment. RESULTS: The mean change in serum phosphate was -1.29 mg/dl (95% confidence interval, -1.63 to -0.96 mg/dl) in the ferric citrate hydrate group and 0.06 mg/dl (95% confidence interval, -0.20 to 0.31 mg/dl) in the placebo group (P<0.001 for difference between groups). The percentage of patients achieving target serum phosphate levels was 64.9% in the ferric citrate hydrate group and 6.9% in the placebo group (P<0.001). Fibroblast growth factor-23 concentrations were significantly lower in patients treated with ferric citrate hydrate versus placebo (change from baseline [median], -142.0 versus 67.0 pg/ml; P<0.001). Ferric citrate hydrate significantly increased serum iron, ferritin, and transferrin saturation compared with placebo (P=0.001 or P<0.001). Five patients discontinued active treatment because of treatment-emergent adverse events with ferric citrate hydrate treatment versus one patient with placebo. Overall, adverse drug reactions were similar in patients receiving ferric citrate hydrate or placebo, with gastrointestinal disorders occurring in 30.0% of ferric citrate hydrate patients and 26.7% of patients receiving placebo. CONCLUSION: In patients with nondialysis-dependent CKD, 12-week treatment with ferric citrate hydrate resulted in significant reductions in serum phosphate and fibroblast growth factor-23 while simultaneously increasing serum iron parameters.

Primary study

Unclassified

Journal Kidney international
Year 2014
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Efficacy of PA21 (sucroferric oxyhydroxide), a novel calcium-free polynuclear iron(III)-oxyhydroxide phosphate binder, was compared with that of sevelamer carbonate in an open-label, randomized, active-controlled phase III study. Seven hundred and seven hemo- and peritoneal dialysis patients with hyperphosphatemia received PA21 1.0-3.0 g per day and 348 received sevelamer 4.8-14.4 g per day for an 8-week dose titration, followed by 4 weeks without dose change, and then 12 weeks maintenance. Serum phosphorus reductions at week 12 were -0.71 mmol/l (PA21) and -0.79 mmol/l (sevelamer), demonstrating non-inferiority of, on average, three tablets of PA21 vs. eight of sevelamer. Efficacy was maintained to week 24. Non-adherence was 15.1% (PA21) vs. 21.3% (sevelamer). The percentage of patients that reported at least one treatment-emergent adverse event was 83.2% with PA21 and 76.1% with sevelamer. A higher proportion of patients withdrew owing to treatment-emergent adverse events with PA21 (15.7%) vs. sevelamer (6.6%). Mild, transient diarrhea, discolored feces, and hyperphosphatemia were more frequent with PA21; nausea and constipation were more frequent with sevelamer. After 24 weeks, 99 hemodialysis patients on PA21 were re-randomized into a 3-week superiority analysis of PA21 maintenance dose in 50 patients vs. low dose (250 mg per day (ineffective control)) in 49 patients. The PA21 maintenance dose was superior to the low dose in maintaining serum phosphorus control. Thus, PA21 was effective in lowering serum phosphorus in dialysis patients, with similar efficacy to sevelamer carbonate, a lower pill burden, and better adherence.

Primary study

Unclassified

Authors Wada K , Wada Y
Journal Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy
Year 2014
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Vascular calcification (VC) contributes to cardiovascular disease in hemodialysis (HD) patients, especially with diabetes mellitus (DM) complications. No randomized studies have been published regarding the effect of lanthanum carbonate (LC) on VC progression in DM patients. The aim of this study was to evaluate the effects of lanthanum carbonate on the progression of VC in HD patients with type 2 DM. We conducted a randomized controlled trial comparing LC with calcium carbonate (CC) in 43 HD patients at a single dialysis center. Estimations of aortic calcification index (ACI) by abdominal computed tomography were performed twice for each patient (at baseline and 12 months). Forty-one patients completed the study (19 LC, 22 CC). When ACI at baseline was ≦0.48 (median of baseline ACI), median change in ACI (Δ%ACI) was 20.44 (11.50-36.80%) in the LC group, and 40.00 (33.30-92.60%) in the CC group (P = 0.026). On the other hand, when ACI at baseline was >0.48, the median change in ACI (Δ%ACI) was 6.42 (3.13-24.40%) in the LC group, and 8.08 (5.68-12.20%) in the CC group (P = 1.000). Serum markers of chronic kidney disease-mineral and bone disorder (CKD-MBD), HbA1c, dose of vitamin D analogues, and side-effects of medications did not change in either group throughout the study except int-PTH increased in the LC group. This study indicated that administration of LC inhibited the progression of VC in patients receiving HD for type 2 DM, only in cases of slight VC compared with CC.

Primary study

Unclassified

Journal Journal of cardiovascular pharmacology and therapeutics
Year 2013
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BACKGROUND AND OBJECTIVES: Coronary artery calcification (CAC) is associated with future cardiovascular events and/or death of patients on hemodialysis (HD). We investigated whether progression of CAC in patients on HD could be delayed by switching from a calcium (Ca)-based phosphate (Pi) binder to lanthanum carbonate. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: The CAC scores were evaluated at study enrollment and after 6 months in 52 patients on HD using calcium carbonate (CC) as a Pi binder. Patients were randomly divided into 2 groups assigned to receive either CC or lanthanum carbonate (LC), and the CAC scores were evaluated after a 6-month treatment period. Progression of CAC was assessed, as were serum levels of Ca, Pi, and intact parathyroid hormone (iPTH). RESULTS: Forty-two patients completed the study (23 receiving CC and 19 receiving LC). In the 6 months prior to randomization, all patients were treated with CC. During this 6-month period, the CAC scores increased significantly in all 42 patients. Once randomized, there was significantly less progression in the group treated with LC than with CC. Changes in CAC scores from 6 to 12 months were significantly smaller in the LC group than the CC group (-288.9 ± 1176.4 vs 107.1 ± 559.6, P = .036), and percentage changes were also significantly different (-6.4% vs 41.2%, P = .024). Serum Ca, Pi, and iPTH levels were similar in both groups during the study period. CONCLUSIONS: This pilot study suggested that LC delayed progression of CAC in patients on HD compared with CC.