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

Registration Number: EUCTR2018-000175-33-RO

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 182

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 for HFrEF and treated according tolocally recognized guidelines with both drugs and devices, as appropriate.
8. Individuals 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. Symptomatic hypotension or systolic blood pressure (BP) <95 mmHg on 2 consecutive measurements.
5. Receiving dialysis or anticipated by the investigator to require dialysis therapy within 3 months.
6. 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.
7. Addison’s disease or other causes of hypoaldosteronism.
8. Known hypersensitivity to sodium zirconium cyclosilicate (ZS).
9. 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.
10. Active malignancy requiring treatment.
11. Current treatment with mineralocorticoid receptor antagonist (MRA), including spironolactone, eplerenone, canrenone, canrenoate, or finerenone, at any dose at enrolment.
12. 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.
13. Treated with potassium supplements within 7 days prior to randomization.
14. Participation in another clinical study with ZS at any time or treatment with any investigational product (IP) during the last 3 months.
15. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff, AstraZeneca representatives, and/or staff at the study site).
16. 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.
17. Previous randomisation in the present study.

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 ZS and placebo in RAAS blockade treatment.;Secondary Objective: - To determine if there is a difference between ZS and placebo in RAAS blockade treatment in subjects with Potassium Measured using an i-<br>STAT Device (i-STAT-K) > 5.0 mmol/L at last assessment before randomization<br>- To determine if there is a difference between ZS and placebo in RAAS blockade treatment in subjects with i-STAT-K = 5.0 mmol/L at last assessment before randomization;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: End of study treatment, approximately at 3 months after 1st study drug administration

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Proportion of subjects in the following categories at 3 months with i-STAT-K > 5.0 mmol/L at last assessment before randomization: <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<br><br>2. Proportion of subjects in the following categories at 3 months with i-STAT-K = 5.0 mmol/L at last assessment before randomization: <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: End of study treatment, approximately at 3 months after 1st study drug administration

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