A Randomized Clinical Trial to Define the Best Strategy for the Management of Heart Failure and Chronic Kidney Disease.
NCT Number: NCT06578078
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Heart Failure|Chronic Kidney Diseases
Interventions: DRUG: Sodium Zirconium Cyclosilicate|DRUG: Standard of care treatment (RAASi therapy)
Sponsor: Fundación para la Investigación del Hospital Clínico de Valencia
Sex: ALL
Age: OLDER_ADULT
Enrollment: 94
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09-30
Completion Date: 2026-03-30
Locations: Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, 28922, Spain|Hospital Universitario Severo Ochoa, Leganés, Madrid, 28914, Spain|Hospital Universitario Nuestra Señora del Perpétuo Socorro, Albacete, 02006, Spain|Hospital Universitario de Burgos, Burgos, 09006, Spain|Hospital Universitario Reina Sofía, Córdoba, 14004, Spain|Hospital Clínico Universitario de Valencia, Valencia, 46010, Spain

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.

Primary Outcome Measures: 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 Outcome Measures: 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), To assess the number of patients achieving at least 50% of the target dose of RAASi recommended in the guidelines., 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), To assess the number of patients achieving at least 50% of the target dose of RAASi recommended in the guidelines., Through study completion, an average of 3 months
Other Outcome Measures: 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), To assess the number of patients that achieve at least 50% of the target dose recommended in guidelines of Mineralocorticoid receptor antagonist (MRA)., 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), To assess the number of patients that achieve at least 50% of the target dose recommended in guidelines of Mineralocorticoid receptor antagonist (MRA), 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), To analyse the number of patients achieving at least 50% of the recommended target dose of MRA and achieving at least 50% of the guidelines recommended target dose of RAASi, Through study completion, an average of 3 months|Number of patients increasing 50% of MRA and RAASi doses since the screening visit (V0) to 3 months after study inclusion (V9), To analyse the number of patients achieving at least 50% of the recommended target dose of MRA and achieving at least 50% of the guidelines recommended target dose of RAASi, Through study completion, an average of 3 months|Number of patients achieving the target doses of RAASi since the screening visit (V0) to 3 months after study inclusion (V9), To evaluate the number of patients achieving the target dose recommended in guidelines of RAASi., Through study completion, an average of 3 months|Proportion of patients in each group requiring a down titration of RAASi and/or MRA over the study period, To evaluate the number of patients requiring down titration and discontinuation of RAASi and/or MRA during the study, Through study completion, an average of 3 months|Proportion of patients in each group requiring up titration of RAASi and/or MRA following down titration of RAASi and/or MRA, To evaluate the number of patients requiring down titration and discontinuation of RAASi and/or MRA during the study, Through study completion, an average of 3 months|Proportion of patients in each group requiring discontinuation of RAASi and/or MRA over the study period., To evaluate the number of patients requiring down titration and discontinuation of RAASi and/or MRA during the study, Through study completion, an average of 3 months|Number of patients achieving at least 50% of the target doses of RAASi since the screening visit (V0) to 1 month after study inclusion, To analyse the number of patients achieving 50% of target doses recommended in guidelines of RAASi at 1 month after study inclusion, Through study completion, an average of 3 months|Number of patients increasing 50% of RAASi doses since the screening visit (V0) to 1 month after study inclusion, To analyse the number of patients achieving 50% of target doses recommended in guidelines of RAASi at 1 month after study inclusion, Through study completion, an average of 3 months|Number of patients achieving a decrease of at least 5% in NT-proBNP levels since the baseline visit (V1) to 3 months after study inclusion (V9)., To determine surrogate short-term (90 days) efficacy objective of changes in biomarker levels (NT-proBNP and CA125) evaluated as a decrease of at least 5% from baseline to 3 months after study inclusion., Through study completion, an average of 3 months|Mean Change in NT-proBNP levels since the baseline visit (V1) to 3 months after study inclusion (V9)., To determine surrogate short-term (90 days) efficacy objective of changes in biomarker levels (NT-proBNP and CA125) evaluated as a decrease of at least 5% from baseline to 3 months after study inclusion., Through study completion, an average of 3 months|Number of patients achieving a decrease of at least 5% in CA125 levels since the baseline visit (V1) to 3 months after study inclusion (V9)., To determine surrogate short-term (90 days) efficacy objective of changes in biomarker levels (NT-proBNP and CA125) evaluated as a decrease of at least 5% from baseline to 3 months after study inclusion., Through study completion, an average of 3 months|Mean Change in CA125 levels since the baseline visit (V1) to 3 months after study inclusion (V9)., To determine surrogate short-term (90 days) efficacy objective of changes in biomarker levels (NT-proBNP and CA125) evaluated as a decrease of at least 5% from baseline to 3 months after study inclusion., Through study completion, an average of 3 months|Mean change on Systolic arterial blood pressure measurement from baseline visit (V1) to 3 months after study inclusion (V9)., To explore changes in systolic arterial blood pressure at baseline and 3 months after study inclusion., Through study completion, an average of 3 months|Mean change from baseline visit (V1) measured at 3 months after study inclusion (V9) in the overall summary score of KKCQ, as a specific HF patient reported outcome questionnaire., To explore the effect of treatment with SZC versus none on Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score., Through study completion, an average of 3 months|To determine the change in renal function the Mean Change in UACR and Mean change in HCO3 will be calculated between baseline visit (V1) and 3 months after study inclusion (V9), To evaluate changes in renal function at baseline and 3 months after study inclusion between both groups, Through study completion, an average of 3 months|Number of patients decreasing at least 40% the eGFR since the screening visit (V0) to 3 months after study inclusion (V9)., To analyse the number of patients that decrease at least 40% in estimated glomerular filtration rate (eGFR) by the CDK-EPI formula., Through study completion, an average of 3 months|Mean change from baseline visit (V1) measured at 3 months after study inclusion (V9) in the overall summary score of KDQoL, as a specific CKD patient reported outcome questionnaire., To explore the effect of treatment with SZC versus none on the Kidney Disease Questionnaire of life (KDQoL) Overall Summary Score., Through study completion, an average of 3 months|Number of visits for HF/HK/impaired renal function/hypertension or hyperkalemia diagnosed in the outpatient clinic., To determine the number of visits to the emergency department for HF/HK/impaired renal function/hypertension (defined as BP over 200 and/or 100 mmHg) and hyperkalemia diagnosed in the outpatient clinic., Through study completion, an average of 3 months|Proportion of patients requiring hospitalization for HF/HK/impaired renal function over the study period., To analyse the number of admissions for HF/HK/impaired renal function., Through study completion, an average of 3 months|Mean number of hospitalizations per patient for HF/HK/impaired renal function over the study period., To analyse the number of admissions for HF/HK/impaired renal function., Through study completion, an average of 3 months|Proportion of patients presenting at least one clinical event over the study period, To evaluate in both experimental groups the combined endpoint of visits to the emergency department or admission for HF/HK/impaired renal function or decrease of at least 40% in estimated glomerular filtration rate (eGFR) by the CDK-EPI formula or death from cardiovascular causes., Through study completion, an average of 3 months|Proportion of patients presenting more than one clinical event over the study period, To evaluate in both experimental groups the combined endpoint of visits to the emergency department or admission for HF/HK/impaired renal function or decrease of at least 40% in estimated glomerular filtration rate (eGFR) by the CDK-EPI formula or death from cardiovascular causes., Through study completion, an average of 3 months|Proportion of patients presenting all clinical events over the study period, To evaluate in both experimental groups the combined endpoint of visits to the emergency department or admission for HF/HK/impaired renal function or decrease of at least 40% in estimated glomerular filtration rate (eGFR) by the CDK-EPI formula or death from cardiovascular causes., Through study completion, an average of 3 months|Percentage of patients treated with and without sodium-glucose cotransporter-2 (SGLT2) inhibitors over the study period in both arms, To analyse the percentage of patients with HF treated with and without sodium-glucose cotransporter-2 (SGLT2) inhibitors., Through study completion, an average of 3 months|Mean Change in Mg levels since the baseline visit (V1) to 3 months after study inclusion (V9)., To explore changes in Mg levels at baseline and 3 months after study inclusion., Through study completion, an average of 3 months|Proportion of patients presenting each clinical outcome over the study period: Adverse events, Serious adverse events, Changes in clinical laboratory parameters, Changes in vital signs and ECGs, To evaluate the safety and tolerability of SZC in this patient population., Through study completion, an average of 3 months