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Randomized clinical trial of the iron-based phosphate binder PA21 in hemodialysis patients.

ABSTRACT: A dose-finding study was undertaken to investigate the efficacy of PA21, a novel polynuclear iron(III)-oxyhydroxide phosphate binder.In a randomized, active-controlled, multicenter, open-label study at 50 clinical sites in Europe and the United States, hemodialysis patients were randomized to PA21 at dosages of 1.25, 5.0, 7.5, 10.0, or 12.5 g/d or sevelamer-HCl 4.8 g/d for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus concentration from baseline.There were 154 participants who were randomized and received the study drug. All groups except PA21 1.25 g/d showed a significant decrease in serum phosphorus. Mean decreases in serum phosphorus in PA21 10 g/d and 12.5 g/d were -2.00±1.71 mg/dl and -1.69±1.81 mg/dl, respectively. A similar decrease to sevelamer-HCl (-1.06±1.35 mg/dl) was seen with PA21 5.0 g/d (-1.08±2.12 mg/dl) and 7.5 g/d (-1.25±1.21 mg/d). Overall, 60.9% of participants randomized to PA21 and 57.7% randomized to sevelamer-HCl reported ?1 adverse event. The most frequent adverse events were hypophosphatemia (18.0%) and discolored feces (11.7%) for the pooled PA21 dose groups, and diarrhea, hypophosphatemia, and hypotension (each 11.5%) for sevelamer-HCl. Discontinuation due to adverse events occurred at a similar rate in PA21-treated (21.1%) and sevelamer-HCl-treated (23.1%) participants.PA21 5-12.5 g/d significantly reduces serum phosphorus in hemodialysis patients. The 5 g/d and 7.5 g/d dosages showed similar efficacy to 4.8 g/d of sevelamer-HCl. The adverse events rate was similar for PA21 and sevelamer-HCl.

SUBMITTER: Wuthrich RP

PROVIDER: S-EPMC3562865 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Randomized clinical trial of the iron-based phosphate binder PA21 in hemodialysis patients.

Wüthrich Rudolf P RP Chonchol Michel M Covic Adrian A Gaillard Sylvain S Chong Edward E Tumlin James A JA

Clinical journal of the American Society of Nephrology : CJASN 20121102 2

<h4>Background and objectives</h4>A dose-finding study was undertaken to investigate the efficacy of PA21, a novel polynuclear iron(III)-oxyhydroxide phosphate binder.<h4>Design, setting, participants, & measurements</h4>In a randomized, active-controlled, multicenter, open-label study at 50 clinical sites in Europe and the United States, hemodialysis patients were randomized to PA21 at dosages of 1.25, 5.0, 7.5, 10.0, or 12.5 g/d or sevelamer-HCl 4.8 g/d for 6 weeks. The primary efficacy endpoi ...[more]

PMID: 23124782

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Project description:BackgroundPatients with end-stage renal disease (ESRD) require phosphate binders for hyperphosphatemia and erythropoiesis-stimulating agents (ESAs) and intravenous (i.v.) iron for anemia. Ferric citrate (FC) is a novel, iron-based phosphate binder that increases iron stores and decreases i.v. 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 i.v. 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 designThe study was a randomized, controlled clinical trial.Setting and populationA total of 441 adult subjects with ESRD who received FC or AC for 52 weeks were included.Model, perspective, and timelineDifferences in ESA and i.v. 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.OutcomesStudy outcomes were costs saved/patient/year using FC versus AC (US dollars).ResultsOur model suggests an annual decrease of 129,106 U of ESAs and 1960 mg of i.v. 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 i.v. iron: a total of $2101/patient/year; these savings would be expected to double for managed care plans.LimitationsThe projections were made on 1 year of trial data.ConclusionsPhosphate binding with FC reduces i.v. iron and ESA usage. Given the high cost burden of ESRD, our model demonstrates significant potential cost savings.Trial registrationClinicalTrials.gov (NCT01191255) http://clinicaltrials.gov/ct2/show/NCT01191255 .

Project description:BACKGROUND: Despite the evidence that phosphate binder (PB) is associated with improved outcomes many hemodialysis patients do not adhere to prescribed PB regimen. Therefore, barriers to PB adherence should be identified and eliminated. The purpose of this study was to evaluate PB adherence among hemodialysis patients and to explore potentially modifiable factors associated with low PB adherence. METHODS: A cross-sectional study (502 patients) was performed in four dialysis units in Salvador, Brazil, using data from the second phase of the Prospective Study of the Prognosis of Chronic Hemodialysis Patients (PROHEMO). Patients were categorized as adherent or non-adherent to PB based on their responses to a semi-structured questionnaire. RESULTS: Non-adherence to PB was observed for 65.7% of the patients. After adjustments for numerous covariates, cerebrovascular disease (odds ratio (OR), 3.30; 95% confidence interval (CI), 1.03-10.61), higher PTH (OR per each 300 pg/mL, 1.14; 95% CI, 1.01-1.28), lack of comprehension of the appropriate time to use PB (OR, 7.09; 95% CI, 2.10-23.95) and stopping PB use after feeling better (OR, 4.54; 95% CI, 1.45-14.25) or feeling worse (OR, 11.04; 95% CI, 1.79- 68.03) were significantly associated with PB non-adherence. By contrast, the adjusted odds of PB non-adherence were lower for patients with more years on dialysis (OR by each 2 years, 0.87; 95% CI, 0.80-0.95), with serum phosphorus above 5.5 mg/dL (OR, 0.53; 95% CI 0.34-0.82), who referred that were encouraged by the dialysis staff to be independent (OR, 0.52; 95% CI 0.30-0.90), and reported that the nephrologist explained how PB should be used (OR, 0.20; 95% CI 0.05-0.73). CONCLUSION: The results of the present study are encouraging by showing evidence that improvement in the care provided by the dialysis staff and the attending nephrologist may play an important role in reducing the high prevalence of non-adherence to PB in maintenance hemodialysis patients. A new questionnaire is presented and may help to evaluate systematically the patients regarding PB adherence in hemodialysis setting.

Project description: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.52-week, open-label, phase 3, randomized, controlled trial for safety-profile assessment.Maintenance dialysis patients with serum phosphorus levels ?6.0 mg/dL after washout of prior phosphate binders.2:1 randomization to ferric citrate or active control (sevelamer carbonate and/or calcium acetate).Changes in mineral bone disease, protein-energy wasting/inflammation, and occurrence of adverse events after 1 year.Serum calcium, intact parathyroid hormone, phosphorus, aluminum, white blood cell count, percentage of lymphocytes, serum urea nitrogen, and bicarbonate.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±2.25 mg/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±0.95 mg/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±392.1 pg/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.Open-label study, few peritoneal dialysis patients.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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Randomized clinical trial of the iron-based phosphate binder PA21 in hemodialysis patients.

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Randomized clinical trial of the iron-based phosphate binder PA21 in hemodialysis patients.

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