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Jürgen Floege - One of the best experts on this subject based on the ideXlab platform.
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effects of sucroferric oxyhydroxide and Sevelamer Carbonate on chronic kidney disease mineral bone disorder parameters in dialysis patients
Nephrology Dialysis Transplantation, 2019Co-Authors: Markus Ketteler, Viatcheslav Rakov, Anjay Rastogi, Bruce Spinowitz, Adrian Covic, Stuart M. Sprague, Sebastian Walpen, Jürgen FloegeAbstract:BACKGROUND Treatment of hyperphosphataemia is the primary goal of chronic kidney disease-mineral and bone disorder (CKD-MBD) management. This post hoc analysis of a randomized, Phase 3 study evaluated the effects of 1-year treatment with the phosphate binders sucroferric oxyhydroxide or Sevelamer Carbonate ('Sevelamer') on CKD-MBD indices among dialysis patients with hyperphosphataemia. METHODS After a 2- to 4-week washout from previous phosphate binders, 1059 patients were randomized 2:1 to sucroferric oxyhydroxide 1.0-3.0 g/day (n = 710) or Sevelamer 2.4-14.4 g/day (n = 349) for up to 24 weeks. Eligible patients enrolled in a 28-week extension. This post hoc analysis was performed for patients who completed ≥1 year of continuous treatment (n = 549). As the treatment groups showed similar CKD-MBD outcomes, the data were pooled for this analysis. RESULTS Phosphate-binder therapy was associated with significant and sustained 30% reductions in serum phosphorus (P < 0.001). Median intact fibroblast growth factor-23 (FGF-23) also significantly decreased (P < 0.001) by 64% over 1 year. Intact parathyroid hormone decreased significantly after 24 weeks (P < 0.001), but levels returned to near baseline values by Week 52; minimal changes in serum calcium were observed. Of the bone resorption markers evaluated, tartrate-resistant acid phosphatase 5b (TRAP5b) decreased significantly (P < 0.001), whereas CTx increased transiently but returned to baseline levels by Week 52. The bone formation markers bone-specific alkaline phosphatase and osteocalcin both increased over 1 year of treatment. CONCLUSIONS Overall, 1 year of sucroferric oxyhydroxide or Sevelamer treatment significantly reduced serum FGF-23, which has been associated with clinical benefit in patients with CKD. The trend towards increased bone formation marker levels indicates a beneficial effect on bone metabolism.
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one year efficacy and safety of the iron based phosphate binder sucroferric oxyhydroxide in patients on peritoneal dialysis
Nephrology Dialysis Transplantation, 2017Co-Authors: Jürgen Floege, Viatcheslav Rakov, Anjay Rastogi, Bruce Spinowitz, Laura J Lisk, Johannes F.e. Mann, Markus Ketteler, Adrian Covic, Stuart M. SpragueAbstract:Background: Sucroferric oxyhydroxide is a noncalcium, iron-based phosphate binder that demonstrated sustained serum phosphorus control, good tolerability and lower pill burden compared with Sevelamer Carbonate (Sevelamer) in a Phase 3 study conducted in dialysis patients. This subanalysis examines the efficacy and tolerability of sucroferric oxyhydroxide and Sevelamer in the peritoneal dialysis (PD) patient population. Methods: The initial study (NCT01324128) and its extension (NCT01464190) were multicenter, Phase 3, open-label, randomized (2:1), active-controlled trials comparing sucroferric oxyhydroxide (1.0-3.0 g/day) with Sevelamer (2.4-14.4 g/day) in dialysis patients over 52 weeks in total. Results: In the overall study, 84/1055 (8.1%) patients received PD and were eligible for efficacy analysis (sucroferric oxyhydroxide, n = 56; Sevelamer, n = 28). The two groups were broadly comparable to each other and to the overall study population. Serum phosphorus concentrations decreased comparably with both phosphate binders by week 12 (mean change from baseline - 0.6 mmol/L). Over 52 weeks, sucroferric oxyhydroxide effectively reduced serum phosphorus concentrations to a similar extent as Sevelamer; 62.5% and 64.3% of patients, respectively, were below the Kidney Disease Outcomes Quality Initiative target range (≤1.78 mmol/L). This was achieved with a lower pill burden (3.4 ± 1.3 versus 8.1 ± 3.7 tablets/day) with sucroferric oxyhydroxide compared with Sevelamer. Treatment adherence rates were 91.2% with sucroferric oxyhydroxide and 79.3% with Sevelamer. The proportion of patients reporting at least one treatment-emergent adverse event was 86.0% with sucroferric oxyhydroxide and 93.1% with Sevelamer. The most common adverse events with both treatments were gastrointestinal: diarrhea and discolored feces with sucroferric oxyhydroxide and nausea, vomiting and constipation with Sevelamer. Conclusions: Sucroferric oxyhydroxide is noninferior to Sevelamer for controlling serum phosphorus in patients undergoing PD, while providing a relatively low pill burden and a high rate of adherence.
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long term effects of the iron based phosphate binder sucroferric oxyhydroxide in dialysis patients
Nephrology Dialysis Transplantation, 2015Co-Authors: Jürgen Floege, Sylvain Gaillard, Anjay Rastogi, Bruce Spinowitz, Edward M F Chong, Laura J Lisk, Johannes F.e. Mann, Markus Ketteler, Adrian Covic, Stuart M. SpragueAbstract:Background. Hyperphosphatemia necessitates the use of phosphate binders in most dialysis patients. Long-term efficacy and tolerability of the iron-based phosphate binder, sucroferric oxyhydroxide (previously known as PA21), was compared with that of Sevelamer Carbonate (Sevelamer) in an open-label Phase III extension study. Methods. In the initial Phase III study, hemo- or peritoneal dialysis patients with hyperphosphatemia were randomized 2:1 to receive sucroferric oxyhydroxide 1.0−3.0 g/day (2−6 tablets/day; n = 710) or Sevelamer 2.4−14.4 g/day (3−18 tablets/day; n = 349) for 24 weeks. Eligible patients could enter the 28-week extension study, continuing the same treatment and dose they were receiving at the end of the initial study. Results. Overall, 644 patients were available for efficacy analysis (n = 384 sucroferric oxyhydroxide; n= 260 Sevelamer). Serum phosphorus concentrations were maintained during the extension study. Mean ± standard deviation (SD) change in serum phosphorus concentrations from extension study baseline to Week 52 end point was 0.02±0.52 mmol/L with sucroferric oxyhydroxide and 0.09±0.58 mmol/L with Sevelamer. Mean serum phosphorus concentrations remained within Kidney Disease Outcomes Quality Initiative target range (1.13– 1.78 mmol/L) for both treatment groups. Mean (SD) daily tablet number over the 28-week extension study was lower for
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a phase iii study of the efficacy and safety of a novel iron based phosphate binder in dialysis patients
Kidney International, 2014Co-Authors: Jürgen Floege, Sylvain Gaillard, Anjay Rastogi, Edward M F Chong, Laura J Lisk, Markus Ketteler, Adrian Covic, Stuart M. SpragueAbstract: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 1.0–3.0g per day and 348 received Sevelamer 4.8–14.4g 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 -0.71mmol/l (PA21) and -0.79mmol/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 (250mg 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.
Stuart M. Sprague - One of the best experts on this subject based on the ideXlab platform.
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effects of sucroferric oxyhydroxide and Sevelamer Carbonate on chronic kidney disease mineral bone disorder parameters in dialysis patients
Nephrology Dialysis Transplantation, 2019Co-Authors: Markus Ketteler, Viatcheslav Rakov, Anjay Rastogi, Bruce Spinowitz, Adrian Covic, Stuart M. Sprague, Sebastian Walpen, Jürgen FloegeAbstract:BACKGROUND Treatment of hyperphosphataemia is the primary goal of chronic kidney disease-mineral and bone disorder (CKD-MBD) management. This post hoc analysis of a randomized, Phase 3 study evaluated the effects of 1-year treatment with the phosphate binders sucroferric oxyhydroxide or Sevelamer Carbonate ('Sevelamer') on CKD-MBD indices among dialysis patients with hyperphosphataemia. METHODS After a 2- to 4-week washout from previous phosphate binders, 1059 patients were randomized 2:1 to sucroferric oxyhydroxide 1.0-3.0 g/day (n = 710) or Sevelamer 2.4-14.4 g/day (n = 349) for up to 24 weeks. Eligible patients enrolled in a 28-week extension. This post hoc analysis was performed for patients who completed ≥1 year of continuous treatment (n = 549). As the treatment groups showed similar CKD-MBD outcomes, the data were pooled for this analysis. RESULTS Phosphate-binder therapy was associated with significant and sustained 30% reductions in serum phosphorus (P < 0.001). Median intact fibroblast growth factor-23 (FGF-23) also significantly decreased (P < 0.001) by 64% over 1 year. Intact parathyroid hormone decreased significantly after 24 weeks (P < 0.001), but levels returned to near baseline values by Week 52; minimal changes in serum calcium were observed. Of the bone resorption markers evaluated, tartrate-resistant acid phosphatase 5b (TRAP5b) decreased significantly (P < 0.001), whereas CTx increased transiently but returned to baseline levels by Week 52. The bone formation markers bone-specific alkaline phosphatase and osteocalcin both increased over 1 year of treatment. CONCLUSIONS Overall, 1 year of sucroferric oxyhydroxide or Sevelamer treatment significantly reduced serum FGF-23, which has been associated with clinical benefit in patients with CKD. The trend towards increased bone formation marker levels indicates a beneficial effect on bone metabolism.
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one year efficacy and safety of the iron based phosphate binder sucroferric oxyhydroxide in patients on peritoneal dialysis
Nephrology Dialysis Transplantation, 2017Co-Authors: Jürgen Floege, Viatcheslav Rakov, Anjay Rastogi, Bruce Spinowitz, Laura J Lisk, Johannes F.e. Mann, Markus Ketteler, Adrian Covic, Stuart M. SpragueAbstract:Background: Sucroferric oxyhydroxide is a noncalcium, iron-based phosphate binder that demonstrated sustained serum phosphorus control, good tolerability and lower pill burden compared with Sevelamer Carbonate (Sevelamer) in a Phase 3 study conducted in dialysis patients. This subanalysis examines the efficacy and tolerability of sucroferric oxyhydroxide and Sevelamer in the peritoneal dialysis (PD) patient population. Methods: The initial study (NCT01324128) and its extension (NCT01464190) were multicenter, Phase 3, open-label, randomized (2:1), active-controlled trials comparing sucroferric oxyhydroxide (1.0-3.0 g/day) with Sevelamer (2.4-14.4 g/day) in dialysis patients over 52 weeks in total. Results: In the overall study, 84/1055 (8.1%) patients received PD and were eligible for efficacy analysis (sucroferric oxyhydroxide, n = 56; Sevelamer, n = 28). The two groups were broadly comparable to each other and to the overall study population. Serum phosphorus concentrations decreased comparably with both phosphate binders by week 12 (mean change from baseline - 0.6 mmol/L). Over 52 weeks, sucroferric oxyhydroxide effectively reduced serum phosphorus concentrations to a similar extent as Sevelamer; 62.5% and 64.3% of patients, respectively, were below the Kidney Disease Outcomes Quality Initiative target range (≤1.78 mmol/L). This was achieved with a lower pill burden (3.4 ± 1.3 versus 8.1 ± 3.7 tablets/day) with sucroferric oxyhydroxide compared with Sevelamer. Treatment adherence rates were 91.2% with sucroferric oxyhydroxide and 79.3% with Sevelamer. The proportion of patients reporting at least one treatment-emergent adverse event was 86.0% with sucroferric oxyhydroxide and 93.1% with Sevelamer. The most common adverse events with both treatments were gastrointestinal: diarrhea and discolored feces with sucroferric oxyhydroxide and nausea, vomiting and constipation with Sevelamer. Conclusions: Sucroferric oxyhydroxide is noninferior to Sevelamer for controlling serum phosphorus in patients undergoing PD, while providing a relatively low pill burden and a high rate of adherence.
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long term effects of the iron based phosphate binder sucroferric oxyhydroxide in dialysis patients
Nephrology Dialysis Transplantation, 2015Co-Authors: Jürgen Floege, Sylvain Gaillard, Anjay Rastogi, Bruce Spinowitz, Edward M F Chong, Laura J Lisk, Johannes F.e. Mann, Markus Ketteler, Adrian Covic, Stuart M. SpragueAbstract:Background. Hyperphosphatemia necessitates the use of phosphate binders in most dialysis patients. Long-term efficacy and tolerability of the iron-based phosphate binder, sucroferric oxyhydroxide (previously known as PA21), was compared with that of Sevelamer Carbonate (Sevelamer) in an open-label Phase III extension study. Methods. In the initial Phase III study, hemo- or peritoneal dialysis patients with hyperphosphatemia were randomized 2:1 to receive sucroferric oxyhydroxide 1.0−3.0 g/day (2−6 tablets/day; n = 710) or Sevelamer 2.4−14.4 g/day (3−18 tablets/day; n = 349) for 24 weeks. Eligible patients could enter the 28-week extension study, continuing the same treatment and dose they were receiving at the end of the initial study. Results. Overall, 644 patients were available for efficacy analysis (n = 384 sucroferric oxyhydroxide; n= 260 Sevelamer). Serum phosphorus concentrations were maintained during the extension study. Mean ± standard deviation (SD) change in serum phosphorus concentrations from extension study baseline to Week 52 end point was 0.02±0.52 mmol/L with sucroferric oxyhydroxide and 0.09±0.58 mmol/L with Sevelamer. Mean serum phosphorus concentrations remained within Kidney Disease Outcomes Quality Initiative target range (1.13– 1.78 mmol/L) for both treatment groups. Mean (SD) daily tablet number over the 28-week extension study was lower for
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a phase iii study of the efficacy and safety of a novel iron based phosphate binder in dialysis patients
Kidney International, 2014Co-Authors: Jürgen Floege, Sylvain Gaillard, Anjay Rastogi, Edward M F Chong, Laura J Lisk, Markus Ketteler, Adrian Covic, Stuart M. SpragueAbstract: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 1.0–3.0g per day and 348 received Sevelamer 4.8–14.4g 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 -0.71mmol/l (PA21) and -0.79mmol/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 (250mg 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.
Markus Ketteler - One of the best experts on this subject based on the ideXlab platform.
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effects of sucroferric oxyhydroxide and Sevelamer Carbonate on chronic kidney disease mineral bone disorder parameters in dialysis patients
Nephrology Dialysis Transplantation, 2019Co-Authors: Markus Ketteler, Viatcheslav Rakov, Anjay Rastogi, Bruce Spinowitz, Adrian Covic, Stuart M. Sprague, Sebastian Walpen, Jürgen FloegeAbstract:BACKGROUND Treatment of hyperphosphataemia is the primary goal of chronic kidney disease-mineral and bone disorder (CKD-MBD) management. This post hoc analysis of a randomized, Phase 3 study evaluated the effects of 1-year treatment with the phosphate binders sucroferric oxyhydroxide or Sevelamer Carbonate ('Sevelamer') on CKD-MBD indices among dialysis patients with hyperphosphataemia. METHODS After a 2- to 4-week washout from previous phosphate binders, 1059 patients were randomized 2:1 to sucroferric oxyhydroxide 1.0-3.0 g/day (n = 710) or Sevelamer 2.4-14.4 g/day (n = 349) for up to 24 weeks. Eligible patients enrolled in a 28-week extension. This post hoc analysis was performed for patients who completed ≥1 year of continuous treatment (n = 549). As the treatment groups showed similar CKD-MBD outcomes, the data were pooled for this analysis. RESULTS Phosphate-binder therapy was associated with significant and sustained 30% reductions in serum phosphorus (P < 0.001). Median intact fibroblast growth factor-23 (FGF-23) also significantly decreased (P < 0.001) by 64% over 1 year. Intact parathyroid hormone decreased significantly after 24 weeks (P < 0.001), but levels returned to near baseline values by Week 52; minimal changes in serum calcium were observed. Of the bone resorption markers evaluated, tartrate-resistant acid phosphatase 5b (TRAP5b) decreased significantly (P < 0.001), whereas CTx increased transiently but returned to baseline levels by Week 52. The bone formation markers bone-specific alkaline phosphatase and osteocalcin both increased over 1 year of treatment. CONCLUSIONS Overall, 1 year of sucroferric oxyhydroxide or Sevelamer treatment significantly reduced serum FGF-23, which has been associated with clinical benefit in patients with CKD. The trend towards increased bone formation marker levels indicates a beneficial effect on bone metabolism.
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one year efficacy and safety of the iron based phosphate binder sucroferric oxyhydroxide in patients on peritoneal dialysis
Nephrology Dialysis Transplantation, 2017Co-Authors: Jürgen Floege, Viatcheslav Rakov, Anjay Rastogi, Bruce Spinowitz, Laura J Lisk, Johannes F.e. Mann, Markus Ketteler, Adrian Covic, Stuart M. SpragueAbstract:Background: Sucroferric oxyhydroxide is a noncalcium, iron-based phosphate binder that demonstrated sustained serum phosphorus control, good tolerability and lower pill burden compared with Sevelamer Carbonate (Sevelamer) in a Phase 3 study conducted in dialysis patients. This subanalysis examines the efficacy and tolerability of sucroferric oxyhydroxide and Sevelamer in the peritoneal dialysis (PD) patient population. Methods: The initial study (NCT01324128) and its extension (NCT01464190) were multicenter, Phase 3, open-label, randomized (2:1), active-controlled trials comparing sucroferric oxyhydroxide (1.0-3.0 g/day) with Sevelamer (2.4-14.4 g/day) in dialysis patients over 52 weeks in total. Results: In the overall study, 84/1055 (8.1%) patients received PD and were eligible for efficacy analysis (sucroferric oxyhydroxide, n = 56; Sevelamer, n = 28). The two groups were broadly comparable to each other and to the overall study population. Serum phosphorus concentrations decreased comparably with both phosphate binders by week 12 (mean change from baseline - 0.6 mmol/L). Over 52 weeks, sucroferric oxyhydroxide effectively reduced serum phosphorus concentrations to a similar extent as Sevelamer; 62.5% and 64.3% of patients, respectively, were below the Kidney Disease Outcomes Quality Initiative target range (≤1.78 mmol/L). This was achieved with a lower pill burden (3.4 ± 1.3 versus 8.1 ± 3.7 tablets/day) with sucroferric oxyhydroxide compared with Sevelamer. Treatment adherence rates were 91.2% with sucroferric oxyhydroxide and 79.3% with Sevelamer. The proportion of patients reporting at least one treatment-emergent adverse event was 86.0% with sucroferric oxyhydroxide and 93.1% with Sevelamer. The most common adverse events with both treatments were gastrointestinal: diarrhea and discolored feces with sucroferric oxyhydroxide and nausea, vomiting and constipation with Sevelamer. Conclusions: Sucroferric oxyhydroxide is noninferior to Sevelamer for controlling serum phosphorus in patients undergoing PD, while providing a relatively low pill burden and a high rate of adherence.
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long term effects of the iron based phosphate binder sucroferric oxyhydroxide in dialysis patients
Nephrology Dialysis Transplantation, 2015Co-Authors: Jürgen Floege, Sylvain Gaillard, Anjay Rastogi, Bruce Spinowitz, Edward M F Chong, Laura J Lisk, Johannes F.e. Mann, Markus Ketteler, Adrian Covic, Stuart M. SpragueAbstract:Background. Hyperphosphatemia necessitates the use of phosphate binders in most dialysis patients. Long-term efficacy and tolerability of the iron-based phosphate binder, sucroferric oxyhydroxide (previously known as PA21), was compared with that of Sevelamer Carbonate (Sevelamer) in an open-label Phase III extension study. Methods. In the initial Phase III study, hemo- or peritoneal dialysis patients with hyperphosphatemia were randomized 2:1 to receive sucroferric oxyhydroxide 1.0−3.0 g/day (2−6 tablets/day; n = 710) or Sevelamer 2.4−14.4 g/day (3−18 tablets/day; n = 349) for 24 weeks. Eligible patients could enter the 28-week extension study, continuing the same treatment and dose they were receiving at the end of the initial study. Results. Overall, 644 patients were available for efficacy analysis (n = 384 sucroferric oxyhydroxide; n= 260 Sevelamer). Serum phosphorus concentrations were maintained during the extension study. Mean ± standard deviation (SD) change in serum phosphorus concentrations from extension study baseline to Week 52 end point was 0.02±0.52 mmol/L with sucroferric oxyhydroxide and 0.09±0.58 mmol/L with Sevelamer. Mean serum phosphorus concentrations remained within Kidney Disease Outcomes Quality Initiative target range (1.13– 1.78 mmol/L) for both treatment groups. Mean (SD) daily tablet number over the 28-week extension study was lower for
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a phase iii study of the efficacy and safety of a novel iron based phosphate binder in dialysis patients
Kidney International, 2014Co-Authors: Jürgen Floege, Sylvain Gaillard, Anjay Rastogi, Edward M F Chong, Laura J Lisk, Markus Ketteler, Adrian Covic, Stuart M. SpragueAbstract: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 1.0–3.0g per day and 348 received Sevelamer 4.8–14.4g 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 -0.71mmol/l (PA21) and -0.79mmol/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 (250mg 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.
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effects of phosphate binders in moderate ckd
Journal of The American Society of Nephrology, 2012Co-Authors: Geoffrey A Block, Bryan Kestenbaum, Markus Ketteler, David Spiegel, David C Wheeler, Martha S Persky, Matthew A Allison, John R Asplin, Gerard Smits, Andrew N HoofnagleAbstract:Some propose using phosphate binders in the CKD population given the association between higher levels of phosphorus and mortality, but their safety and efficacy in this population are not well understood. Here, we aimed to determine the effects of phosphate binders on parameters of mineral metabolism and vascular calcification among patients with moderate to advanced CKD. We randomly assigned 148 patients with estimated GFR=20-45 ml/min per 1.73 m(2) to calcium acetate, lanthanum Carbonate, Sevelamer Carbonate, or placebo. The primary endpoint was change in mean serum phosphorus from baseline to the average of months 3, 6, and 9. Serum phosphorus decreased from a baseline mean of 4.2 mg/dl in both active and placebo arms to 3.9 mg/dl with active therapy and 4.1 mg/dl with placebo (P=0.03). Phosphate binders, but not placebo, decreased mean 24-hour urine phosphorus by 22%. Median serum intact parathyroid hormone remained stable with active therapy and increased with placebo (P=0.002). Active therapy did not significantly affect plasma C-terminal fibroblast growth factor 23 levels. Active therapy did, however, significantly increase calcification of the coronary arteries and abdominal aorta (coronary: median increases of 18.1% versus 0.6%, P=0.05; abdominal aorta: median increases of 15.4% versus 3.4%, P=0.03). In conclusion, phosphate binders significantly lower serum and urinary phosphorus and attenuate progression of secondary hyperparathyroidism among patients with CKD who have normal or near-normal levels of serum phosphorus; however, they also promote the progression of vascular calcification. The safety and efficacy of phosphate binders in CKD remain uncertain.
Kausik Umanath - One of the best experts on this subject based on the ideXlab platform.
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the phosphate binder ferric citrate and mineral metabolism and inflammatory markers in maintenance dialysis patients results from prespecified analyses of a randomized clinical trial
American Journal of Kidney Diseases, 2015Co-Authors: Peter N Van Buren, Mohammed Sika, John P Middleton, Josephine D Abraham, Safa Arfeen, Tom Greene, Kausik Umanath, Julia B. Lewis, Jamie P. Dwyer, Isai G BowlineAbstract:Background Phosphate binders are the cornerstone of hyperphosphatemia management in dialysis patients. Ferric citrate is an iron-based oral phosphate binder that effectively lowers serum phosphorus levels. Study Design 52-week, open-label, phase 3, randomized, controlled trial for safety-profile assessment. Setting & Participants Maintenance dialysis patients with serum phosphorus levels ≥6.0mg/dL after washout of prior phosphate binders. Intervention 2:1 randomization to ferric citrate or active control (Sevelamer Carbonate and/or calcium acetate). Outcomes Changes in mineral bone disease, protein-energy wasting/inflammation, and occurrence of adverse events after 1 year. Measurements Serum calcium, intact parathyroid hormone, phosphorus, aluminum, white blood cell count, percentage of lymphocytes, serum urea nitrogen, and biCarbonate. Results There were 292 participants randomly assigned to ferric citrate, and 149, to active control. Groups were well matched. For mean changes from baseline, phosphorus levels decreased similarly in the ferric citrate and active control groups (−2.04±1.99 [SD] vs −2.18±2.25mg/dL, respectively; P =0.9); serum calcium levels increased similarly in the ferric citrate and active control groups (0.22±0.90 vs 0.31±0.95mg/dL; P =0.2). Hypercalcemia occurred in 4 participants receiving calcium acetate. Parathyroid hormone levels decreased similarly in the ferric citrate and active control groups (−167.1±399.8 vs −152.7±392.1pg/mL; P =0.8). Serum albumin, biCarbonate, serum urea nitrogen, white blood cell count and percentage of lymphocytes, and aluminum values were similar between ferric citrate and active control. Total and low-density lipoprotein cholesterol levels were lower in participants receiving Sevelamer than those receiving ferric citrate and calcium acetate. Fewer participants randomly assigned to ferric citrate had serious adverse events compared with active control. Limitations Open-label study, few peritoneal dialysis patients. Conclusions Ferric citrate was associated with similar phosphorus control compared to active control, with similar effects on markers of bone and mineral metabolism in dialysis patients. There was no evidence of protein-energy wasting/inflammation or aluminum toxicity, and fewer participants randomly assigned to ferric citrate had serious adverse events. Ferric citrate is an effective phosphate binder with a safety profile comparable to Sevelamer and calcium acetate.
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Ferric Citrate, an Iron-Based Phosphate Binder, Reduces Health Care Costs in Patients on Dialysis Based on Randomized Clinical Trial Data
Drugs in R&D, 2015Co-Authors: Roger A. Rodby, Mohammed Sika, Kausik Umanath, Robert Niecestro, T. Christopher Bond, Julia Lewis, Jamie P. DwyerAbstract:Background Patients with end-stage renal disease (ESRD) require phosphate binders for hyperphosphatemia and erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron for anemia. Ferric citrate (FC) is a novel, iron-based phosphate binder that increases iron stores and decreases IV iron and ESA usage while maintaining hemoglobin levels, and may decrease the cost of ESRD care. The study objectives were to (1) quantify differences in ESA and IV iron usage among ESRD patients receiving FC compared with active control (AC) (Sevelamer Carbonate and/or calcium acetate) on the basis of data from a 52-week phase III clinical trial and (2) standardize trial data to the general United States (US) ESRD population and calculate the potential impact of FC on ESRD cost/patient/year in the USA. Study Design The study was a randomized, controlled clinical trial. Setting and Population A total of 441 adult subjects with ESRD who received FC or AC for 52 weeks were included. Model, Perspective, and Timeline Differences in ESA and IV iron usage between the treatment groups were modeled over time using generalized linear mixed models and zero-inflated Poisson models. Trends were modeled via logarithmic curves, and utilization patterns were applied to the general dialysis population to estimate expected resource savings. Outcomes Study outcomes were costs saved/patient/year using FC versus AC (US dollars). Results Our model suggests an annual decrease of 129,106 U of ESAs and 1960 mg of IV iron per patient in the second year after a switch from AC to FC. Applying 2013 Medicare pricing, this would save $1585 in ESAs and $516 in IV iron: a total of $2101/patient/year; these savings would be expected to double for managed care plans. Limitations The projections were made on 1 year of trial data. Conclusions Phosphate binding with FC reduces IV iron and ESA usage. Given the high cost burden of ESRD, our model demonstrates significant potential cost savings. Trial Registration ClinicalTrials.gov (NCT01191255) http://clinicaltrials.gov/ct2/show/NCT01191255 .
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ferric citrate an iron based phosphate binder reduces health care costs in patients on dialysis based on randomized clinical trial data
Drugs in R & D, 2015Co-Authors: Roger A. Rodby, Mohammed Sika, Christopher T Bond, Kausik Umanath, Robert Niecestro, Julia B. Lewis, Jamie P. DwyerAbstract:Background Patients with end-stage renal disease (ESRD) require phosphate binders for hyperphosphatemia and erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron for anemia. Ferric citrate (FC) is a novel, iron-based phosphate binder that increases iron stores and decreases IV iron and ESA usage while maintaining hemoglobin levels, and may decrease the cost of ESRD care. The study objectives were to (1) quantify differences in ESA and IV iron usage among ESRD patients receiving FC compared with active control (AC) (Sevelamer Carbonate and/or calcium acetate) on the basis of data from a 52-week phase III clinical trial and (2) standardize trial data to the general United States (US) ESRD population and calculate the potential impact of FC on ESRD cost/patient/year in the USA.
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ferric citrate reduces intravenous iron and erythropoiesis stimulating agent use in esrd
Journal of The American Society of Nephrology, 2015Co-Authors: Kausik Umanath, Dana Negoi, Steven Zeig, Diana Jalal, Barbara A Greco, Ebele M Umeukeje, Efrain Reisin, John Manley, Anand N Hiremath, Samuel S BlumenthalAbstract:Ferric citrate (FC) is a phosphate binder with shown efficacy and additional effects on iron stores and use of intravenous (iv) iron and erythropoiesis-stimulating agents (ESAs). We provide detailed analyses of changes in iron/hematologic parameters and iv iron/ESA use at time points throughout the active control period of a phase 3 international randomized clinical trial. In all, 441 subjects were randomized (292 to FC and 149 to Sevelamer Carbonate and/or calcium acetate [active control (AC)]) and followed for 52 weeks. Subjects on FC had increased ferritin and transferrin saturation (TSAT) levels compared with subjects on AC by week 12 (change in ferritin, 114.1±29.35 ng/ml; P P P P P =0.04). Overall, 90.3% of subjects on FC and 89.3% of subjects on AC experienced adverse events. In conclusion, treatment with FC as a phosphate binder results in increased iron parameters apparent after 12 weeks and reduces iv iron and ESA use while maintaining hemoglobin over 52 weeks, with a safety profile similar to that of available binders.
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ferric citrate reduces intravenous iron and erythropoiesis stimulating agent use in esrd
Journal of The American Society of Nephrology, 2015Co-Authors: Kausik Umanath, Dana Negoi, Steven Zeig, Diana Jalal, Barbara A Greco, Ebele M Umeukeje, Efrain Reisin, John Manley, Anand N Hiremath, Samuel S BlumenthalAbstract:Ferric citrate (FC) is a phosphate binder with shown efficacy and additional effects on iron stores and use of intravenous (iv) iron and erythropoiesis-stimulating agents (ESAs). We provide detailed analyses of changes in iron/hematologic parameters and iv iron/ESA use at time points throughout the active control period of a phase 3 international randomized clinical trial. In all, 441 subjects were randomized (292 to FC and 149 to Sevelamer Carbonate and/or calcium acetate [active control (AC)]) and followed for 52 weeks. Subjects on FC had increased ferritin and transferrin saturation (TSAT) levels compared with subjects on AC by week 12 (change in ferritin, 114.1±29.35 ng/ml; P<0.001; change in TSAT, 8.62%±1.57%; P<0.001). Change in TSAT plateaued at this point, whereas change in ferritin increased through week 24, remaining relatively stable thereafter. Subjects on FC needed less iv iron compared with subjects on AC over 52 weeks (median [interquartile range] dose=12.9 [1.0-28.9] versus 26.8 [13.4-47.6] mg/wk; P<0.001), and the percentage of subjects not requiring iv iron was higher with FC (P<0.001). Cumulative ESA over 52 weeks was lower with FC than AC (median [interquartile range] dose=5303 [2023-9695] versus 6954 [2664-12,375] units/wk; P=0.04). Overall, 90.3% of subjects on FC and 89.3% of subjects on AC experienced adverse events. In conclusion, treatment with FC as a phosphate binder results in increased iron parameters apparent after 12 weeks and reduces iv iron and ESA use while maintaining hemoglobin over 52 weeks, with a safety profile similar to that of available binders.
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Ferric Citrate, an Iron-Based Phosphate Binder, Reduces Health Care Costs in Patients on Dialysis Based on Randomized Clinical Trial Data
Drugs in R&D, 2015Co-Authors: Roger A. Rodby, Mohammed Sika, Kausik Umanath, Robert Niecestro, T. Christopher Bond, Julia Lewis, Jamie P. DwyerAbstract:Background Patients with end-stage renal disease (ESRD) require phosphate binders for hyperphosphatemia and erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron for anemia. Ferric citrate (FC) is a novel, iron-based phosphate binder that increases iron stores and decreases IV iron and ESA usage while maintaining hemoglobin levels, and may decrease the cost of ESRD care. The study objectives were to (1) quantify differences in ESA and IV iron usage among ESRD patients receiving FC compared with active control (AC) (Sevelamer Carbonate and/or calcium acetate) on the basis of data from a 52-week phase III clinical trial and (2) standardize trial data to the general United States (US) ESRD population and calculate the potential impact of FC on ESRD cost/patient/year in the USA. Study Design The study was a randomized, controlled clinical trial. Setting and Population A total of 441 adult subjects with ESRD who received FC or AC for 52 weeks were included. Model, Perspective, and Timeline Differences in ESA and IV iron usage between the treatment groups were modeled over time using generalized linear mixed models and zero-inflated Poisson models. Trends were modeled via logarithmic curves, and utilization patterns were applied to the general dialysis population to estimate expected resource savings. Outcomes Study outcomes were costs saved/patient/year using FC versus AC (US dollars). Results Our model suggests an annual decrease of 129,106 U of ESAs and 1960 mg of IV iron per patient in the second year after a switch from AC to FC. Applying 2013 Medicare pricing, this would save $1585 in ESAs and $516 in IV iron: a total of $2101/patient/year; these savings would be expected to double for managed care plans. Limitations The projections were made on 1 year of trial data. Conclusions Phosphate binding with FC reduces IV iron and ESA usage. Given the high cost burden of ESRD, our model demonstrates significant potential cost savings. Trial Registration ClinicalTrials.gov (NCT01191255) http://clinicaltrials.gov/ct2/show/NCT01191255 .
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the phosphate binder ferric citrate and mineral metabolism and inflammatory markers in maintenance dialysis patients results from prespecified analyses of a randomized clinical trial
American Journal of Kidney Diseases, 2015Co-Authors: Peter N Van Buren, Mohammed Sika, John P Middleton, Josephine D Abraham, Safa Arfeen, Tom Greene, Kausik Umanath, Julia B. Lewis, Jamie P. Dwyer, Isai G BowlineAbstract:Background Phosphate binders are the cornerstone of hyperphosphatemia management in dialysis patients. Ferric citrate is an iron-based oral phosphate binder that effectively lowers serum phosphorus levels. Study Design 52-week, open-label, phase 3, randomized, controlled trial for safety-profile assessment. Setting & Participants Maintenance dialysis patients with serum phosphorus levels ≥6.0mg/dL after washout of prior phosphate binders. Intervention 2:1 randomization to ferric citrate or active control (Sevelamer Carbonate and/or calcium acetate). Outcomes Changes in mineral bone disease, protein-energy wasting/inflammation, and occurrence of adverse events after 1 year. Measurements Serum calcium, intact parathyroid hormone, phosphorus, aluminum, white blood cell count, percentage of lymphocytes, serum urea nitrogen, and biCarbonate. Results There were 292 participants randomly assigned to ferric citrate, and 149, to active control. Groups were well matched. For mean changes from baseline, phosphorus levels decreased similarly in the ferric citrate and active control groups (−2.04±1.99 [SD] vs −2.18±2.25mg/dL, respectively; P =0.9); serum calcium levels increased similarly in the ferric citrate and active control groups (0.22±0.90 vs 0.31±0.95mg/dL; P =0.2). Hypercalcemia occurred in 4 participants receiving calcium acetate. Parathyroid hormone levels decreased similarly in the ferric citrate and active control groups (−167.1±399.8 vs −152.7±392.1pg/mL; P =0.8). Serum albumin, biCarbonate, serum urea nitrogen, white blood cell count and percentage of lymphocytes, and aluminum values were similar between ferric citrate and active control. Total and low-density lipoprotein cholesterol levels were lower in participants receiving Sevelamer than those receiving ferric citrate and calcium acetate. Fewer participants randomly assigned to ferric citrate had serious adverse events compared with active control. Limitations Open-label study, few peritoneal dialysis patients. Conclusions Ferric citrate was associated with similar phosphorus control compared to active control, with similar effects on markers of bone and mineral metabolism in dialysis patients. There was no evidence of protein-energy wasting/inflammation or aluminum toxicity, and fewer participants randomly assigned to ferric citrate had serious adverse events. Ferric citrate is an effective phosphate binder with a safety profile comparable to Sevelamer and calcium acetate.
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ferric citrate an iron based phosphate binder reduces health care costs in patients on dialysis based on randomized clinical trial data
Drugs in R & D, 2015Co-Authors: Roger A. Rodby, Mohammed Sika, Christopher T Bond, Kausik Umanath, Robert Niecestro, Julia B. Lewis, Jamie P. DwyerAbstract:Background Patients with end-stage renal disease (ESRD) require phosphate binders for hyperphosphatemia and erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron for anemia. Ferric citrate (FC) is a novel, iron-based phosphate binder that increases iron stores and decreases IV iron and ESA usage while maintaining hemoglobin levels, and may decrease the cost of ESRD care. The study objectives were to (1) quantify differences in ESA and IV iron usage among ESRD patients receiving FC compared with active control (AC) (Sevelamer Carbonate and/or calcium acetate) on the basis of data from a 52-week phase III clinical trial and (2) standardize trial data to the general United States (US) ESRD population and calculate the potential impact of FC on ESRD cost/patient/year in the USA.