P0242SUBGROUP EFFICACY ANALYSIS OF SODIUM ZIRCONIUM CYCLOSILICATE (SZC) IN HYPERKALAEMIC HAEMODIALYSIS PATIENTS IN THE DIALIZE STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Kieran McCafferty ◽  
Steven Fishbane ◽  
Bruce Spinowitz ◽  
Anjay Rastogi ◽  
Martin Ford ◽  
...  
Keyword(s):  
Rescue Therapy ◽  
Normal Serum ◽  
Dose Titration ◽  
Efficacy Analysis ◽  
Sodium Zirconium ◽  
Titration Phase ◽  
Evaluation Phase ◽  
Baseline Weight ◽  
Sodium Zirconium Cyclosilicate ◽  
Patient Subgroups

Abstract Background and Aims Patients with end-stage renal disease have severely reduced renal potassium excretion and many require haemodialysis (3 days/week) to maintain normal serum potassium (sK+). The phase 3b DIALIZE study (NCT03303521) showed that sodium zirconium cyclosilicate (SZC) reduces predialysis sK+ after the long interdialytic interval and is well tolerated in haemodialysis patients with hyperkalaemia. This post-hoc analysis of the DIALIZE data assessed the efficacy of SZC in patient subgroups. Method The DIALIZE study randomised 196 patients 1:1 to placebo (n=99) or SZC (n=97). The study consisted of an 8-week treatment period, comprising a 4-week SZC dose titration phase followed by a 4-week evaluation phase. The starting dose of SZC was 5 g orally once daily on non-dialysis days (4 days/week) for the 4-week dose titration phase (titrated in 5 g increments to a maximum of 15 g) to achieve predialysis sK+ 4.0–5.0 mmol/L. Patients maintained a stable SZC dose for the 4-week evaluation phase (SZC 5, 10 or 15 g). Here, we assessed the proportion of treatment responders, i.e. those who during the 4-week evaluation phase achieved predialysis sK+ of 4.0–5.5 mmol/L during ≥3 of 4 haemodialysis treatments after the long interdialytic interval and who did not require potassium-lowering rescue therapy. Treatment responders were stratified by patient subgroups: sex, country, race, age (years), baseline weight (kg) and baseline sK+ (mmol/L). Results For patients receiving SZC, at baseline 59% were male, mean age was 55.7 years, 52% were white, 11% were Black or African American and 34% were Asian, and mean predialysis sK+ was 5.8 mmol/L. Using a predialysis sK+ range of 4.0–5.5 mmol/L, 69.1% (n=67/97) of SZC patients and 19.2% (n=19/99) of placebo patients were deemed treatment responders. Response to SZC was generally consistent across patient subgroups vs placebo for sex, country, race, age, baseline weight and baseline sK+, with some variation between subgroup subcategories (Table). Conclusion Our results suggest that SZC is generally effective across all groups of haemodialysis patients with hyperkalaemia. SZC responder rates for some patient subgroup subcategories were limited by low patient numbers.

P0220EFFECTIVENESS OF SODIUM ZIRCONIUM CYCLOSILICATE (SZC) IN HAEMODIALYSIS PATIENTS WITH SEVERE HYPERKALAEMIA IN THE DIALIZE STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Martin Ford ◽  
Steven Fishbane ◽  
Bruce Spinowitz ◽  
Anjay Rastogi ◽  
Nicolas Guzman ◽  
...  
Keyword(s):  
Rescue Therapy ◽  
Adverse Outcomes ◽  
Dose Titration ◽  
Once Daily ◽  
Sodium Zirconium ◽  
Titration Phase ◽  
Evaluation Phase ◽  
Starting Dose ◽  
Post Hoc ◽  
Sodium Zirconium Cyclosilicate

Abstract Background and Aims Patients with severe hyperkalaemia require urgent intervention to avoid serious adverse outcomes and mortality. The phase 3b DIALIZE study (NCT03303521) showed that sodium zirconium cyclosilicate (SZC) reduces predialysis serum potassium (sK+) after the long interdialytic interval and is well tolerated in haemodialysis patients with hyperkalaemia. This post-hoc analysis of the DIALIZE data assessed the efficacy of SZC in patients with severe hyperkalaemia (defined as sK+ ≥6.0 mmol/L) at baseline. Method The DIALIZE study randomised 196 patients 1:1 to placebo (n=99) or SZC (n=97). The study consisted of an 8-week treatment period, comprising a 4-week SZC dose titration phase followed by a 4-week evaluation phase. The starting dose of SZC was 5 g orally once daily on non-dialysis days (4 days/week) for the 4-week dose titration phase (titrated in 5 g increments to a maximum of 15 g on non-dialysis days) to achieve predialysis sK+ 4.0–5.0 mmol/L. Patients maintained a stable dose of SZC for the 4-week evaluation phase (SZC 5, 10 or 15 g). Here, treatment response was defined as achievement of predialysis sK+ of 4.0–5.5 mmol/L during ≥3 of 4 haemodialysis treatments after the long interdialytic interval during the 4-week evaluation phase and not requiring potassium-lowering rescue therapy. Rates of response were compared between those patients with and without baseline severe hyperkalaemia (sK+ ≥6 mmol/L and <6 mmol/L, respectively). The sK+ measurement on Visit 1 (Day –7) was used as the baseline value. Results At baseline, 88 patients had sK+ ≥6 mmol/L (SZC n=46, placebo n=42) and 106 patients had sK+ <6 mmol/L (SZC n=49, placebo n=57); data were missing for two SZC patients. The overall proportion of treatment responders (irrespective of treatment and dose) in patients with baseline sK+ ≥6 mmol/L and <6 mmol/L was 44.3% and 43.4%, respectively. The proportion of treatment responders was greater with SZC compared with placebo in patients with baseline sK+ ≥6 mmol/L and sK+ <6 mmol/L (Figure). For patients receiving SZC, the proportion of treatment responders was consistent in those with baseline sK+ ≥6 mmol/L (67.4%) compared with those with baseline sK+ <6 mmol/L (71.4%; Figure). Conclusion Our results suggest that SZC is effective in haemodialysis patients with severe hyperkalaemia.

scholarly journals A Phase 3b, Randomized, Double-Blind, Placebo-Controlled Study of Sodium Zirconium Cyclosilicate for Reducing the Incidence of Predialysis Hyperkalemia

2019 ◽  
Vol 30 (9) ◽  
pp. 1723-1733 ◽  
Author(s):  
Steven Fishbane ◽  
Martin Ford ◽  
Masafumi Fukagawa ◽  
Kieran McCafferty ◽  
Anjay Rastogi ◽  
...  
Keyword(s):  
Serum Potassium ◽  
Rescue Therapy ◽  
Controlled Study ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Interdialytic Weight Gain ◽  
Sodium Zirconium ◽  
Efficacy Outcome ◽  
Sodium Zirconium Cyclosilicate

BackgroundPatients with ESRD have minimal renal potassium excretion and, despite hemodialysis, often have persistent predialysis hyperkalemia. The DIALIZE study (NCT03303521) evaluated sodium zirconium cyclosilicate (SZC) in the management of hyperkalemia in hemodialysis patients.MethodsIn the DIALIZE study, a double-blind, placebo-controlled, phase 3b multicenter study, we randomized adults with ESRD who were managed by three-times weekly hemodialysis and had predialysis hyperkalemia to receive placebo or SZC 5 g once daily on non-dialysis days, and titrated towards maintaining normokalemia over 4 weeks, in 5 g increments to a maximum of 15 g. The primary efficacy outcome was proportion of patients during the 4-week stable-dose evaluation period who maintained predialysis serum potassium of 4.0–5.0 mmol/L during at least three of four hemodialysis treatments after the long interdialytic interval and did not require urgent rescue therapy to reduce serum potassium.ResultsIn total, 196 patients (mean [standard deviation (SD)] age =58.1 [13.7] years old) were randomized to sodium zirconium cyclosilicate or placebo. Of 97 patients receiving sodium zirconium cyclosilicate, 41.2% met the primary end point and were deemed treatment responders compared with 1.0% of 99 patients receiving placebo (P<0.001). Rescue therapy to reduce serum potassium during the treatment period was required by 2.1% of patients taking sodium zirconium cyclosilicate versus 5.1% taking placebo. Serious adverse events occurred in 7% and 8% of patients in sodium zirconium cyclosilicate and placebo groups, respectively. The two groups displayed comparable interdialytic weight gain. There were few episodes of hypokalemia.ConclusionsSodium zirconium cyclosilicate is an effective and well-tolerated treatment for predialysis hyperkalemia in patients with ESRD undergoing adequate hemodialysis.

Managing Hyperkalemia: Stepping Into a New Frontier

2016 ◽  
Vol 30 (5) ◽  
pp. 557-561 ◽  
Author(s):  
Antony Q. Pham ◽  
Jessica Sexton ◽  
Dexter Wimer ◽  
Isha Rana ◽  
Timothy Nguyen
Keyword(s):  
Action Potentials ◽  
Normal Serum ◽  
The Body ◽  
Sodium Polystyrene Sulfonate ◽  
Polystyrene Sulfonate ◽  
Novel Treatments ◽  
Cellular Processes ◽  
Sodium Zirconium ◽  
New Frontier ◽  
Sodium Zirconium Cyclosilicate

Maintaining potassium balance in the body is essential for cellular function. Even a slight increase in normal serum potassium levels (3.5-5.0 mEq/L) can interfere with metabolism, electrical action potentials, and cellular processes. Hyperkalemia is commonly seen in patients with chronic kidney disease (CKD) and in patients on renin–angiotensin–aldosterone system (RAAS) inhibitors. Sodium polystyrene sulfonate (SPS), diuretics, and hemodialysis are currently available methods for removing potassium from the body; however, these options have their limitations. Patiromer (Veltassa) and sodium zirconium cyclosilicate are 2 new therapeutic options that can potentially lead a new frontier in the management of hyperkalemia. This article will review these novel treatments.

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