Randomized Clinical Trial of the Iron-Based Phosphate Binder PA21 in Hemodialysis Patients

Abstract

SummaryBackground 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 22.0061.71 mg/dl and 21.6961.81 mg/dl, respectively. A similar decrease to sevelamer-HCl (21.0661.35 mg/dl) was seen with PA21 5.0 g/d (21.0862.12 mg/dl) and 7.5 g/d (21.2561.21 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.

Effects and safety of iron-based phosphate binders in dialysis patients: a systematic review and meta-analysis

“…The remaining 18 full-text articles were reviewed for more detailed assessment, and 10 studies were excluded because of duplicate reports. Finally, 8 studies [15][16][17][18][19][20][21][22] with 2018 participants met our inclusion criteria and were included in our meta-analysis. The selection process for studies included in the systematic review is shown in Figure 1.…”

“…Seven studies [15][16][17][18][19]21,22 were parallel randomized controlled trials, while one study 20 was cross-over randomized controlled trial. Three studies 17,18,22 compared iron-based phosphate binders with placebo, four studies 16,17,19,21 made comparison between iron-based phosphate binders and sevelamer, and one study 20 compared ferric citrate with calcium carbonate. Of the eight included trials, five 15,17,[20][21][22] were conducted in Asia.…”

“…Of the eight included trials, five 15,17,[20][21][22] were conducted in Asia. Two studies 16,17 recruited both hemodialysis and peritoneal dialysis patients and six studies 15,[18][19][20][21][22] included only hemodialysis patients. Six studies 15,16,[19][20][21][22] made dietary recommendations or monitored the dietary phosphate intake for the participants.…”

“…Random sequence generations were adequate in three studies. 18,19,22 Allocation concealments were adequately described with low risk of bias in two studies 18,22 and unclear in other six studies. Participants and investigators were blinded in three studies 17,18,22 and outcome assessors were blinded in four studies.…”

“…Only three studies 15,18,22 were analyzed on an intention-to-treat basis. Five studies 17,[19][20][21][22] were supported by the production or sales manufacturer and declared conflicts of interest.…”