Chronic Kidney Diseases, Heart Failure
Conditions
Brief summary
Heart failure (HF) and Chronic Kidney Disease (CKD) patients are frequently not administered renin-angiotensin aldosterone system inhibitor (RAASi) therapies at recommended doses due to hyperkalaemia, despite proven mortality and morbidity benefits. Sodium zirconium cyclosilicate (SZC) is a nonabsorbed potassium binder proven to lower serum potassium (S-K) and maintain normokalaemia. The purpose is to assess if a treatment regimen containing SZC will allow RAASi therapies to be optimized to target doses in patients with heart failure, chronic kidney disease and elevated serum potassium or at risk of developing elevated serum potassium.
Detailed description
This is a randomized clinical trial, multicentre, parallel group, open label, to evaluate the use of sodium zirconium cyclosilicate (SZC) to optimize RAASi therapy in patients with heart failure and chronic kidney disease, through up-titration of ACEi, ARB, ARNI or MRA therapy according to clinical guidelines (1), without inducing clinically significant hyperkalemia. Eligible subjects will have been admitted to hospital because of an HF (NYHA I- III) decompensation, will have required intravenous diuretics and will have had mild hyperkalaemic values that needed stabilization or be at risk of developing hyperkalaemia. Subjects will be randomised in a 1:1 ratio to receive SZC or none (standard of care treatment without potassium binders) for 3 months while optimizing RAASi therapies according to the European Society of Cardiology (ESC) guidelines.
Interventions
Use of sodium zirconium cyclosilicate to optimize RAASi therapy, through up-titration of ACEi, ARB, ARNI or MRA therapy according to clinical guidelines
DRUGStandard of care treatment (RAASi therapy)
Standard of care treatment (RAASi therapy) without use of sodium zirconium cyclosilicate
Sponsors
Fundación para la Investigación del Hospital Clínico de Valencia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a randomised clinical trial, multicentre, open label, of RAASi associated with SZC versus modification of RAASi without added chelator in patients over 70 years of age, who after the stabilization of an acute HF episode and comorbid CKD, have HK or are at high risk of developing HK.
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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. * Provision of informed consent form prior to any study specific procedures, sampling and analysis. * Individuals must be ≥ 70 years of age at the time of signing the informed consent form. * Individuals must have a confirmed diagnosis of Heart Failure (HF) according to clinical practice guidelines NYHA functional class I-III (with HFrEF or HFpEF). * Individuals must have previously been admitted to hospital due to HF decompensation requiring intravenous diuretics. * Individuals must have been stabilised for at least 24-48h of their HF decompensation before randomisation. * Individuals must have a confirmed diagnosis of Chronic Kidney Disease defined as a renal impairment of eGFR less than 60ml/min/1.73 m2. * Individuals receiving background standard of care for HF and treated according to international guidelines. Specific treatment should include RAASi and/or MRA treatment and at least should have been stable for ≥ 4 weeks at maximum tolerated doses. * Patients on RAASi blocker treatment with less than or equal to 75% of the maximum recommended dose. * Hyperkalemic patients (sK+ 5.1-5.9 mmol/L at screening / study enrolment) or Normokalemic patients at risk of developing HK defining as having a history of hyperkalaemia (sK+ \>5.0 mEq/L) within the prior 24 months and sK+ ≥4.5 mEq/L ≤ 5.1 mEq/L at inclusion
Exclusion criteria
* Limited life expectancy (less than 1 year) according to clinician's criteria, such as but not limited to malignancy, with life expectancy of less than 2 years based on investigator's clinical judgement. * sK \>6 mEq/litre or \<4.5mEq/litre or history of hypokalemic episodes (S-K\<3.5 mEq/L) during the last year. * Patients on haemodialysis or haemofiltration * NYHA functional class IV * Patients undergoing treatment with potassium binders. * Active tumour undergoing chemotherapy or metastasis or malignancy requiring treatment. * Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted. * QTc(f) \> 550 msec. * History of QT prolongation associated with other medications that required discontinuation of that medication. * Congenital long QT syndrome. * Prior history of hypersensitivity to a RAAS blocker drug, including but not limited to development of angioedema, icterus, hepatitis, or neutropenia or thrombocytopenia requiring treatment modification. Addison's disease or other causes of hypoaldosteronism. * Patients with a known hypersensitivity to SZC or any of the excipients of the product. * Individuals 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. * Treated with potassium supplements within 7 days prior to randomization. 15. Positive hepatitis C antibody hepatitis B virus surface antigen or hepatitis B virus core antibody, at screening. * Known to have tested positive for human immunodeficiency virus. * Known history of drug or alcohol abuse within 3 year of screening. * Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site). * 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. * Previous enrolment in the present study. * Participation in another clinical study with an investigational product during the last 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients increasing at least 25% of the target doses of RAASi since the screening visit (V0) to 3 months after study inclusion (V9) | Through study completion, an average of 3 months | To compare the number of patients achieving an increase of at least 25% of RAASi according to guideline-recommended target doses, in the arm treated with Lokelma plus RAASi versus the arm treated with RAASi without K+ binder, at 3 months after study inclusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients achieving at least 50% of the target doses of RAASi since the screening visit (V0) to 3 months after study inclusion (V9) | Through study completion, an average of 3 months | To assess the number of patients achieving at least 50% of the target dose of RAASi recommended in the guidelines. |
| Number of patients increasing 50% of RAASi doses since the screening visit (V0) to 3 months after study inclusion (V9) | Through study completion, an average of 3 months | To assess the number of patients achieving at least 50% of the target dose of RAASi recommended in the guidelines. |
Countries
Spain
Contacts
CONTACTClara Bonanad Lozano
Outcome results
None listed