A three months study evaluating if the potassium binder sodium zirconium cyclosilicate can help manage a common side effect of heart failure treatment, and thereby allow heart failure treatment to be improved

Phase 1

Conditions: Heart Failure
Hyperkalaemia
MedDRA version: 20.0Level: LLTClassification code 10008908Term: Chronic heart failureSystem Organ Class: 100000004849
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: EUCTR2018-000175-33-SK

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 280

Inclusion Criteria

1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
2. Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.
3. Provision of signed and dated written genetic informed consent prior to collection of sample for genetic analysis. Individuals refusing to provide informed consent for genetic testing may still be included in the study, but will not have to provide samples for genetic analysis.
4. Subject must be =18 years of age inclusive, at the time of signing the informed consent form.
5. Individuals with established documented diagnosis of symptomatic heart failure with reduced ejection fraction (HFrEF).
6. Individuals with left ventricular ejection fraction = 40%.
7. Individuals receiving background standard of care (an ACEi, ARB, or ARNI with or without low-dose MRA) for HFrEF and treated according tolocally recognized guidelines with both drugs and devices, as appropriate.
8. Individuals with mild hyperkalaemia or at risk of developing hyperkalaemia during the study.
9. Women of childbearing potential must have a negative pregnancy test during screening (before first dose of investigational product [IP]) performed locally.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 140
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 140

Exclusion Criteria

1. HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis,hypertrophic (obstructive) cardiomyopathy or uncorrected primary valvular disease.
2. Current acute decompensated HF, hospitalization due to decompensated HF within 4 weeks prior to enrolment, or myocardial infarction (MI), unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to enrolment.
3. Coronary revascularization or valvular repair/replacement within 12 weeks prior to enrolment or planned to undergo any of these operations after randomization.
4. Implantation of a Cardiac Resynchronization Therapy (CRT) device or Implantable Cardioverter Defibrillator (ICD) within 12 weeks prior to enrolment or intent to perform atrial fibrillation ablation or to implant a CRT device.
5. Previous cardiac transplantation or implantation of a ventricular assistance device (VAD) or similar device, or transplantation or implantation expected after randomization.
6. Symptomatic bradycardia or second (Mobitz type 2) or third-degree heart block without a pacemaker.
7. Symptomatic hypotension or systolic blood pressure (BP) <95 mmHg on 2 consecutive measurements.
8. Receiving dialysis or anticipated by the investigator to require dialysis therapy within 3 months.
9. Prior history of hypersensitivity to a renin angiotensin aldosterone system inhibitor (RAASi) drug, including but not limited to development of angioedema, icterus, hepatitis, or neutropenia or thrombocytopenia requiring treatment modification.
10. Addison’s disease or other causes of hypoaldosteronism.
11. Known hypersensitivity to sodium zirconium cyclosilicate.
12. Any condition outside the cardiovascular (CV) and renal disease area, such as but not limited to malignancy, with a life expectancy of less than 2 years based on investigator´s clinical judgement.
13. Active malignancy requiring treatment.
14. MRA therapies that are mainly investigational and/or are not widely available as an oral dosing formulation (eg, canrenoate and finerenone) are excluded.
15. Treated with potassium binding resins such as sodium polystyrene sulfonate (SPS; e.g. Kayexalate®) or calcium polystyrene sulfonate (CPS; e.g. Resonium®) or the cation exchange polymer, patiromer sorbitex calcium (Veltassa®) within 7 days prior to the first dose of study drug.
16. Treated with potassium supplements within 7 days prior to randomization.
17. Participation in another clinical study with ZS at any time or treatment with any investigational product (IP) during the last 3 months.
18. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff, AstraZeneca representatives, and/or staff at the study site).
19. Judgment by the investigator that the subject should not participate in the study if the subject is unlikely to comply with study procedures, restrictions and requirements.
20. Previous randomisation in the present study.
21. Subjects with a family history of long QT syndrome, presence of cardiac arrhythmias or conduction defects that require immediate treatment, or a QTc(corrected QT interval) of =550 msec.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine if there is a difference between sodium zirconium cyclosilicate (ZS) and placebo in RAAS (renin angiotensin aldosterone system) blockade treatment.;Secondary Objective: Not applicable;Primary end point(s): Proportion of subjects in the following categories at 3 months:<br>- No ACEi/ARB/ARNI or at less than target dose and no MRA<br>- ACEi/ARB/ARNI at target dose and no MRA<br>- MRA at less than target dose<br>- MRA at target dose;Timepoint(s) of evaluation of this end point: Approximately at 3 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): N/A;Timepoint(s) of evaluation of this end point: N/A

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