Evidence map›Paper›PMID 26011677›Full record

Trial reportEuropean journal of heart failure2015

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.

Stefan D Anker, Mikhail Kosiborod, Faiez Zannad, Ileana L Piña, Peter A McCullough, Gerasimos Filippatos, Peter van der Meer, Piotr Ponikowski, Henrik S Rasmussen, Philip T Lavin and 3 more

Open access · hybridAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in European journal of heart failure, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed, 8 pooled it
12.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

79 citing papers in PubMed, 8 syntheses or guidelines pooled it, 176 citations in OpenAlex.

  1. ASN Kidney Health Guidance on the Cardiovascular-Kidney-Metabolic Syndrome.Journal of the American Society of Nephrology : JASN · 2026
    Guideline
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19 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 11 institutions in 6 countries.

Stefan D AnkerInnovative Clinical Trials, Department of Cardiology & Pneumology, University Medical Centre Göttingen (UMG), Robert-Koch-Strasse 40, D-37075, Göttingen, Germany.
Mikhail KosiborodSaint Luke's Mid America Heart Institute and University of Missouri-Kansas City, Kansas City, MO, USA.
Faiez ZannadInserm, Université de Lorraine, Vandoeuvre-Les-Nancy, France.
Ileana L PiñaAlbert Einstein COM/Montefiore Medical Center, Bronx, NY, USA.
Peter A McCulloughBaylor University Medical Center, Baylor Heart and Vascular Institute, Baylor Jack and Jane Hamilton Heart and Vascular Hospital, Dallas, TX, and The Heart Hospital, Plano, TX, USA.
Gerasimos FilippatosAthens University Hospital Attikon, Athens, Greece.
Peter van der MeerUniversity of Groningen, University Medical Centre Groningen, the Netherlands.
Piotr PonikowskiWroclaw Medical University, Wrocław, Poland.
Henrik S RasmussenZS Pharma, Inc., Coppell, TX, USA.
Philip T LavinBoston Biostatistics Research Foundation, Framingham, MA, USA.
Bhupinder SinghZS Pharma, Inc., Coppell, TX, USA.
Alex YangZS Pharma, Inc., Coppell, TX, USA.
Prakash DeedwaniaUniversity of California San Francisco, CA, USA.
STMicroelectronics (United States) · USAlbert Einstein College of Medicine · USBaylor University Medical Center · USNational Foundation for Cancer Research · USUniversité de Lorraine · FRUniversity General Hospital Attikon · GRUniversity Medical Center Groningen · NLUniversity of California, San Francisco · USUniversity of Göttingen · DEUniversity of Missouri–Kansas City · USWroclaw Medical University · PL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsHyperkalaemia 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

resultsHeart 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.

conclusionCompared 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.

Indexed as

Double-Blind MethodHeart FailureHumansHyperkalemiaPotassiumSilicatesPotassiumSilicatessodium zirconium cyclosilicateheart failurehyperkalaemiaRAASZS-9

Identifiers

PMID26011677
PMCPMC5033065
OpenAlexW2169077241

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.