A study to assess the efficacy and safety of Sodium Zirconium Cyclosilicate (SZC) for the Management of High Potassium in Patients with Symptomatic Heart Failure with Reduced Ejection Fraction and Receiving Spironolactone
- Conditions
- Hyperkalemia in Patients with Symptomatic Heart Failure.MedDRA version: 21.1Level: PTClassification code 10020646Term: HyperkalaemiaSystem Organ Class: 10027433 - Metabolism and nutrition disordersTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2020-003312-27-HU
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 400
- Adults aged =18 years
- Potassium and estimated glomerular filtration rate (eGFR):
- Cohort 1: sK+ 5.1-5.9 mEq/L at screening/study enrolment and eGFR = 30 mL/min/1.73 m2; or
- Cohort 2: Normokalaemic (sK+ 3.5-5.0 mEq/L) at screening and 'at risk' of developing HK defined as any of the following:
- Have a history of HK (sK+ >5.0 mEq/L) within the prior 36 months and eGFR =30 mL/min/1.73 m2, or
- sK+ 4.5-5.0 mEq/L and eGFR 30 to 60 mL/min/1.73 m2, or
- sK+ 4.5-5.0 mEq/L and age >75 years
- Symptomatic HFrEF (New York Heart Association [NYHA] class II-IV), which has been present for at least 3 months
- Left ventricular ejection fraction (LVEF) =40%
- Receiving angiotensin-converting enzyme inhibitor (ACEi), angiotensin II receptor blocker (ARB), or angiotensin receptor-Neprilysin inhibitor (ARNi)
- Not on or on low-dose spironolactone or eplerenone (<25 mg daily).
- Receiving beta-blocker unless contraindicated.
Inclusion Criteria for Proceeding to the 6-month Randomised-Withdrawal Treatment Phase:
- NK (3.5-5.0 mEq/L) on SZC and receiving spironolactone =25 mg daily at the end of the 4- to 6-week run-in phase.
Sex
- Female:
- Female participants of childbearing potential must have a negative pregnancy test (serum).
- Female participants must be 1 year post-menopausal, surgically sterile, or using one highly effective form of birth control (defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly). They should have been stable on their chosen method of birth control for a minimum of 4 months before entering the study and willing to remain on the birth control until 4 weeks after the last dose.
Informed Consent:
- Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this CSP
- Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports Genomic Initiative.
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 214
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 214
- Heart failure due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy, or severe stenotic valve disease as a primary cause of HF
- Current inpatient hospitalisation due to HF with unstable HF, defined as any of the following:
a.SBP <95 mmHg during the 6 hours prior to screening.
b.Intravenous diuretic therapy during the 12 hours prior to screening.
c.Use of intravenous inotropic drugs during the 24 hours prior to screening.
d.Received mechanical circulatory support during the 48 hours prior to screening.
- Type 1 myocardial infarction (MI), unstable angina, or stroke within 12 weeks prior to enrolment
- Coronary revascularisation (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or valvular repair/replacement within 12 weeks prior to enrolment or planned to undergo any of these procedures
- Implantation of a Cardiac Resynchronisation Therapy (CRT) device within 12 weeks prior to enrolment or intent to perform atrial fibrillation ablation or to implant a CRT
device
- Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted.
- Clinically significant bradycardia, as per investigator's judgement, or second- or thirddegree heart block without a pacemaker
- Previous cardiac transplantation or implantation of a ventricular assistance device (VAD) or similar device, or transplantation or implantation expected after randomisation
- History of gynecomastia due to spironolactone therapy requiring down-titration or discontinuation of spironolactone, or switch to a different MRA
Other Exclusions:
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
- Judgement by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions and requirements.
- Previous enrolment in the present study.
- For women only - breast-feeding or planning to become pregnant during the study.
- If the participant has evidence of Coronavirus disease 2019 (COVID-19) within 2 weeks prior to enrolment (see Appendix E), the participant cannot be enrolled in the study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method