Dataset Information

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

ABSTRACT:

Background and objectives

A dose-finding study was undertaken to investigate the efficacy of PA21, a novel polynuclear iron(III)-oxyhydroxide phosphate binder.

Design, setting, participants, & measurements

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.

Results

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.

Conclusions

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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Publications

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:BackgroundCombination therapy with multiple phosphate binders is prescribed to reduce elevated serum phosphorus (sP) concentrations among patients on maintenance hemodialysis. Sucroferric oxyhydroxide (SO), an iron-based phosphate binder, has demonstrated efficacy at reducing sP while also being associated with a low pill burden. Whereas the effects of SO monotherapy have been well characterized in clinical trials and observational cohorts, little is known about the effects of SO-containing combination therapy.MethodsPatients on hemodialysis (N=234) at Fresenius Kidney Care (FKC) who received ≥120 days of uninterrupted phosphate binder combination therapy with SO were included in this retrospective study. Patient data were censored after SO discontinuation, end of care at FKC, or completion of 12 months of follow-up. Quarterly (Q) changes in phosphate binder pill burden, mean sP, and proportion of patients achieving National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI)-recommended sP levels (≤5.5 mg/dl) were compared between baseline (-Q1) and follow-up (Q1-Q4).ResultsPhosphate binder combination therapy with SO was associated with significant increase in the proportion of patients with sP ≤5.5 mg/dl (from 19% at baseline to up to 40% at follow-up; P<0.001) and reduction in sP at all postbaseline time points (from 6.7 mg/dl to 6.2-6.3 mg/dl; P<0.001). Patients on calcium acetate (N=54) and sevelamer (N=94) who added SO therapy at follow-up resulted in a ≥250% increase in patients achieving sP ≤5.5 mg/dl (all P<0.001). Whereas mean phosphate binder pill burden increased with initiation of phosphate binder combination therapy with SO (15.8 pills/d at Q1 versus 12.3 pills/d at -Q1), continued use of SO was associated with down-titration of non-SO phosphate binders such that, by Q4, mean total PB pill burden reduced to 12.3 pills/d.ConclusionsFor patients on hemodialysis with uncontrolled hyperphosphatemia, combination therapy with SO may allow for sustained improvements in sP control without adversely affecting phosphate binder pill burden.

Project description:BackgroundDespite 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.MethodsA 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.ResultsNon-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).ConclusionThe 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.

Dataset Information

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

Background and objectives

Design, setting, participants, & measurements

Results

Conclusions

Publications

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

Similar Datasets

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