Maintenance of serum potassium with sodium zirconium cyclosilicate (ZS-9) in heart failure patients: results from a phase 3 randomized, double-blind, placebo-controlled trial
Aims Hyperkalaemia in heart failure patients limits use of cardioprotective renin–angiotensin–aldosterone system inhibitors (RAASi). Sodium zirconium cyclosilicate (ZS‐9) is a selective potassium ion trap, whose mechanism of action may allow for potassium binding in the upper gastrointestinal tract...
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Published in | European journal of heart failure Vol. 17; no. 10; pp. 1050 - 1056 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
John Wiley & Sons, Ltd
01.10.2015
European Society of Cardiology (Wiley) |
Subjects | |
Online Access | Get full text |
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Summary: | Aims
Hyperkalaemia in heart failure patients limits use of cardioprotective renin–angiotensin–aldosterone system inhibitors (RAASi). Sodium zirconium cyclosilicate (ZS‐9) is a selective potassium ion trap, whose mechanism of action may allow for potassium binding in the upper gastrointestinal tract as early as the duodenum following oral administration. ZS‐9 previously demonstrated the ability to reduce elevated potassium levels into the normal range, with a median time of normalization of 2.2 h and sustain normal potassium levels for 28 days in HARMONIZE—a Phase 3, double‐blind, randomized, placebo‐controlled trial. In the present study we evaluated management of serum potassium with daily ZS‐9 over 28 days in heart failure patients from HARMONIZE, including those receiving RAASi therapies.
Methods and results
Heart failure patients with evidence of hyperkalaemia (serum potassium ≥5.1 mmol/L, n = 94) were treated with open‐label ZS‐9 for 48 h. Patients (n = 87; 60 receiving RAASi) who achieved normokalaemia (potassium 3.5–5.0 mmol/L) were randomized to daily ZS‐9 (5, 10, or 15 g) or placebo for 28 days. Mean potassium and proportion of patients maintaining normokalaemia during days 8–29 post‐randomization were evaluated. Despite RAASi doses being kept constant, patients on 5 g, 10 g, and 15 g ZS‐9 maintained a lower potassium level (4.7 mmol/L, 4.5 mmol/L, and 4.4 mmol/L, respectively) than the placebo group (5.2 mmol/L; P<0.01 vs. each ZS‐9 group); greater proportions of ZS‐9 patients (83%, 89%, and 92%, respectively) maintained normokalaemia than placebo (40%; P < 0.01 vs. each ZS‐9 group). The safety profile was consistent with previously reported overall study population.
Conclusion
Compared with placebo, all three ZS‐9 doses lowered potassium and effectively maintained normokalaemia for 28 days in heart failure patients without adjusting concomitant RAASi, while maintaining a safety profile consistent with the overall study population. |
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Bibliography: | ZS Pharma Inc. istex:8A200311E6316F12FFAC98B08DE39D60F3B56E24 ark:/67375/WNG-20W91CRV-K ArticleID:EJHF300 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-News-3 content type line 23 PMCID: PMC5033065 The copyright line for this article was changed on 13 November 2015 after original online publication. |
ISSN: | 1388-9842 1879-0844 |
DOI: | 10.1002/ejhf.300 |