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J Am Soc Nephrol. 2019 Jun 14. pii: ASN.2019050450. doi: 10.1681/ASN.2019050450. [Epub ahead of print]

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

Author information

1
Department of Medicine, Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York; Sfishbane@northwell.edu.
2
Department of Renal Medicine, King's College Hospital NHS Trust, London, United Kingdom.
3
Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan.
4
Department of Nephrology, Barts Health NHS Trust, London, United Kingdom.
5
Department of Medicine, David Geffen School of Medicine, Los Angeles, California.
6
Department of Medicine, New York-Presbyterian Queens, Queens, New York.
7
Department #2, B. Braun Avitum Russland Clinics, St. Petersburg, Russia.
8
Propedeutics of Internal Diseases Chair, First Pavlov State Medical University of St. Petersburg, St. Petersburg, Russia.
9
Biometrics and Information and.
10
Global Medicines Development, AstraZeneca, Gothenburg, Sweden.
11
Global Medicines Development, AstraZeneca, Gaithersburg, Maryland; and.
12
Department of Renal and Transplant Medicine, Hull University Teaching Hospitals NHS Trust, Hull, United Kingdom.

Abstract

BACKGROUND:

Patients 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.

METHODS:

In 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.

RESULTS:

In 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.

CONCLUSIONS:

Sodium zirconium cyclosilicate is an effective and well-tolerated treatment for predialysis hyperkalemia in patients with ESRD undergoing adequate hemodialysis.

KEYWORDS:

clinical trial; end-stage renal disease; hemodialysis

PMID:
31201218
DOI:
10.1681/ASN.2019050450

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