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Clin J Am Soc Nephrol. 2019 Jun 7;14(6):798-809. doi: 10.2215/CJN.12651018. Epub 2019 May 20.

Sodium Zirconium Cyclosilicate among Individuals with Hyperkalemia: A 12-Month Phase 3 Study.

Author information

1
Division of Nephrology, Department of Medicine, New York-Presbyterian Queens, New York, New York; bss9001@nyp.org.
2
Department of Medicine, Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York.
3
Renal Associates PA, San Antonio, Texas.
4
Renal Research, Gosford, Australia.
5
Section of Nephrology, Advocate Christ Medical Center, University of Illinois at Chicago, Oak Lawn, Illinois.
6
Department of Medicine, University of Mississippi, Jackson, Mississippi.
7
Department of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany.
8
AstraZeneca, Gaithersburg, Maryland.
9
ZS Pharma, Inc. (part of AstraZeneca), San Mateo, California.
10
School of Medicine, University of California, Irvine, Irvine, California.
11
Boston Biostatistics Research Foundation, Framingham, Massachusetts.
12
Department of Internal Medicine, Division of Cardiology, Baylor University Medical Center, Baylor Heart and Vascular Institute, Dallas, Texas.
13
Department of Cardiology, Saint Luke's Mid America Heart Institute, Kansas City, Missouri.
14
Department of Medicine, University of Missouri-Kansas City, Kansas City, Missouri.
15
The George Institute for Global Health, Sydney, Australia.
16
Melbourne Renal Research Group, Reservoir Private Hospital, Reservoir, Australia.
17
Department of Medicine, University of Melbourne, Melbourne, Australia.

Abstract

BACKGROUND AND OBJECTIVES:

Oral sodium zirconium cyclosilicate (formerly ZS-9) binds and removes potassium via the gastrointestinal tract. Sodium zirconium cyclosilicate-associated restoration and maintenance of normokalemia and adverse events were evaluated in a two-part, open label, phase 3 trial.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:

In the correction phase, adult outpatients with plasma potassium ≥5.1 mmol/L (i-STAT Point-of-Care) received sodium zirconium cyclosilicate 10 g three times daily for 24-72 hours until normokalemic (potassium =3.5-5.0 mmol/L). Qualifying participants entered the ≤12-month maintenance phase and received sodium zirconium cyclosilicate 5 g once daily titrated to maintain normokalemia without dietary or medication restrictions. Prespecified primary end points were restoration of normal serum potassium values (3.5-5.0 mmol/L) during the correction phase and maintenance of serum potassium ≤5.1 mmol/L during the maintenance phase. Adverse events were assessed throughout.

RESULTS:

Of 751 participants, 746 (99%) achieved normokalemia during the correction phase (mean serum potassium =4.8 mmol/L; 95% confidence interval, 4.7 to 4.8) and entered the maintenance phase; 466 (63%) participants completed the 12-month trial. Participants were predominantly white, men, and age ≥65 years old; 74% had an eGFR<60 ml/min per 1.73 m2, and 65% used renin-angiotensin-aldosterone system inhibitors. Mean time on sodium zirconium cyclosilicate was 286 days. Mean daily sodium zirconium cyclosilicate dose was 7.2 g (SD=2.6). Over months 3-12, mean serum potassium was 4.7 mmol/L (95% confidence interval, 4.6 to 4.7); mean serum potassium values ≤5.1 and ≤5.5 mmol/L were achieved by 88% and 99% of participants, respectively. Of 483 renin-angiotensin-aldosterone system inhibitor users at baseline, 87% continued or had their dose increased; 11% discontinued. Among 263 renin-angiotensin-aldosterone system inhibitor-naïve participants, 14% initiated renin-angiotensin-aldosterone system inhibitor therapy. Overall, 489 (66%) participants experienced adverse events during the maintenance phase, and 22% experienced a serious adverse event. Of eight (1%) deaths, none were considered related to sodium zirconium cyclosilicate. Nine (1%) and 34 (5%) participants experienced serum potassium <3.0 and 3.0-3.4 mmol/L, respectively.

CONCLUSIONS:

After achieving normokalemia, individualized once daily sodium zirconium cyclosilicate was associated with maintenance of normokalemia without substantial renin-angiotensin-aldosterone system inhibitor changes for ≤12 months.

KEYWORDS:

Confidence Intervals; EGFR protein, human; Gastrointestinal Tract; Outpatients; Plasma; Point-of-Care Systems; Potassium; Receptor, Epidermal Growth Factor; Sodium; Zirconium; antibiotic K 4; chronic kidney disease; hyperkalemia; renin angiotensin system; sodium zirconium cyclosilicate (SZC)

PMID:
31110051
PMCID:
PMC6556727
[Available on 2020-06-07]
DOI:
10.2215/CJN.12651018
[Indexed for MEDLINE]

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