A Clinical Trial to Define the Best Strategy for the Management of Heart Failure in Elderly Patients

NCT06578078 | Recruiting Phase 3

• 2 other identifiers: SENEKA2024-513971-42-00
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 6

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.

Conditions

Heart Failure; Chronic Kidney Diseases

Outcome Measures

Primary Outcomes (1)

• 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)

  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.

  Through study completion, an average of 3 months

Secondary Outcomes (2)

• 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

• 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

Other Outcomes (28)

• Number of patients achieving at least 50% of the target doses of MRA since the screening visit (V0) to 3 months after study inclusion (V9)

  Through study completion, an average of 3 months

• Number of patients increasing 50% of MRA doses since the screening visit (V0) to 3 months after study inclusion (V9)

  Through study completion, an average of 3 months

• Number of patients achieving at least 50% of the target doses of MRA and RAASi since the screening visit (V0) to 3 months after study inclusion (V9)

  Through study completion, an average of 3 months

Study Arms (2)

SZC group

EXPERIMENTAL

Sodium zirconium cyclosilicate with standard of care treatment (RAASi therapy)

Drug: Sodium Zirconium Cyclosilicate

Control group

ACTIVE COMPARATOR

Standard of care treatment (RAASi therapy) without Sodium zirconium cyclosilicate

Drug: Standard of care treatment (RAASi therapy)

Interventions

Sodium Zirconium Cyclosilicate DRUG

Use of sodium zirconium cyclosilicate to optimize RAASi therapy, through up-titration of ACEi, ARB, ARNI or MRA therapy according to clinical guidelines

Also known as: Lokelma

SZC group

Standard of care treatment (RAASi therapy) DRUG

Standard of care treatment (RAASi therapy) without use of sodium zirconium cyclosilicate

Control group

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fundación para la Investigación del Hospital Clínico de Valencia: lead

Study Sites (6)

Hospital Universitario Fundación Alcorcón

Alcorcón, Madrid, 28922, Spain

NOT YET RECRUITING

Hospital Universitario Severo Ochoa

Leganés, Madrid, 28914, Spain

NOT YET RECRUITING

Hospital Universitario Nuestra Señora del Perpétuo Socorro

Albacete, 02006, Spain

RECRUITING

Hospital Universitario de Burgos

Burgos, 09006, Spain

RECRUITING

Hospital Universitario Reina Sofía

Córdoba, 14004, Spain

NOT YET RECRUITING

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

RECRUITING

MeSH Terms

Conditions

Heart Failure; Renal Insufficiency, Chronic

Interventions

sodium zirconium cyclosilicate

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Clara Bonanad Lozano

CONTACT

+34 963156181; clarabonanad@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 27, 2024
• First Posted: August 29, 2024
• Study Start: October 3, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: March 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (6)