SODIUM ZIRCONIUM CYCLOSILICATE for Chronic heart failure | Chronic kidney disease

Inclusion criteria

• {"criterion_text":"- 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."}
• {"criterion_text":"- Hyperkalemic patients (sK+ 5.1–5.9 mmol/L at screening / study enrolment) or Normokalemic"}
• {"criterion_text":"- Provision of informed consent form prior to any study specific procedures, sampling and analysis."}
• {"criterion_text":"- Individuals must be ≥ 70 years of age at the time of signing the informed consent form."}
• {"criterion_text":"- Individuals must have a confirmed diagnosis of Heart Failure (HF) according to clinical practice guidelines NYHA functional class I-III (with HFrEF or HFpEF)."}
• {"criterion_text":"- Individuals must have previously been admitted to hospital due to HF decompensation requiring intravenous diuretics."}
• {"criterion_text":"- Individuals must have been stabilised for at least 24-48h of their HF decompensation before randomisation."}
• {"criterion_text":"- Individuals must have a confirmed diagnosis of Chronic Kidney Disease defined as a renal impairment of eGFR less than 60ml/min/1.73 m2."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Patients on RAASi blocker treatment with less than or equal to 75% of the maximum recommended dose."}

Exclusion criteria

• {"criterion_text":"- 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."}
• {"criterion_text":"- Congenital long QT syndrome."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Patients with a known hypersensitivity to SZC or any of the excipients of the product."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Treated with potassium supplements within 7 days prior to randomization."}
• {"criterion_text":"- Positive hepatitis C antibody hepatitis B virus surface antigen or hepatitis B virus core antibody, at screening."}
• {"criterion_text":"- Known to have tested positive for human immunodeficiency virus."}
• {"criterion_text":"- Known history of drug or alcohol abuse within 3 year of screening."}
• {"criterion_text":"- Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- sK >6 mEq/litre or <4.5mEq/litre or history of hypokalemic episodes (S-K<3.5 mEq/L) during the last year."}
• {"criterion_text":"- Previous enrolment in the present study."}
• {"criterion_text":"- Participation in another clinical study with an investigational product during the last 3 months."}
• {"criterion_text":"- Patients on haemodialysis or haemofiltration"}
• {"criterion_text":"- NYHA functional class IV"}
• {"criterion_text":"- Patients undergoing treatment with potassium binders."}
• {"criterion_text":"- Active tumour undergoing chemotherapy or metastasis or malignancy requiring treatment."}
• {"criterion_text":"- Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted."}
• {"criterion_text":"- QTc(f) > 550 msec."}
• {"criterion_text":"- History of QT prolongation associated with other medications that required discontinuation of that medication."}

Primary endpoints

• {"endpoint_text":"- 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), considering the target dose of each RAASi drug in the ESC guidelines (1).","definition_or_measurement_approach":"Measure: count of patients who increase at least 25% of the target doses of RAASi from screening (V0) to 3 months after inclusion (V9), using ESC guideline target doses for each RAASi drug."}

Secondary endpoints

• {"endpoint_text":"- 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), considering the target dose of each RAASi drug recommended in the ESC guidelines.","definition_or_measurement_approach":"Measure: count of patients achieving ≥50% of ESC guideline target doses of RAASi from V0 to V9 (3 months)."}
• {"endpoint_text":"- Number of patients increasing 50% of RAASi doses since the screening visit (0) to 3 months after study inclusion (V9), considering the target dose of each RAASi drug recommended in the ESC guidelines.","definition_or_measurement_approach":"Measure: count of patients with ≥50% increase in RAASi doses from V0 to V9 (3 months), per ESC targets."}
• {"endpoint_text":"- 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), considering the target dose of each MRA drug recommended in the ESC guidelines.","definition_or_measurement_approach":"Measure: count of patients achieving ≥50% of ESC guideline target doses of MRA from V0 to V9 (3 months)."}
• {"endpoint_text":"- Number of patients increasing 50% of MRA doses since the screening visit (V0) to 3 months after study inclusion (V9), considering the target dose of each MRA drug recommended in the ESC guidelines","definition_or_measurement_approach":"Measure: count of patients with ≥50% increase in MRA doses from V0 to V9 (3 months), per ESC targets."}
• {"endpoint_text":"- Number of patients achieving at least 50% of the target doses of MRA and RAASi since the screening visit (0) to 3 months after study inclusion (V9), considering the target dose recommended in the ESC guidelines","definition_or_measurement_approach":"Measure: count of patients achieving ≥50% of target doses for both MRA and RAASi from V0 to V9 (3 months)."}
• {"endpoint_text":"- Number of patients increasing 50% of MRA and RAASi doses since the screening visit (V0) to 3 months after study inclusion (V9), considering the target dose of each drug recommended in the ESC guidelines","definition_or_measurement_approach":"Measure: count of patients with ≥50% increase in both MRA and RAASi doses from V0 to V9 (3 months)."}
• {"endpoint_text":"- Number of patients achieving the target doses of RAASi since the screening visit (V0) to 3 months after study inclusion (V9), considering the target dose of each RAASi drug recommended in the ESC guidelines","definition_or_measurement_approach":"Measure: count of patients achieving ESC guideline target doses of RAASi at V9 compared to V0."}
• {"endpoint_text":"- Proportion of patients in each group requiring down titration of RAASi and/or MRA over the study period.","definition_or_measurement_approach":"Measure: proportion (%) of patients in each arm requiring down-titration of RAASi and/or MRA during the study period."}
• {"endpoint_text":"- Proportion of patients in each group that required up titration of RAASi and/or MRA following down titration of RAASi and/or MRA.","definition_or_measurement_approach":"Measure: proportion (%) of patients who required up-titration following prior down-titration of RAASi and/or MRA."}
• {"endpoint_text":"- Proportion of patients in each group requiring discontinuation of RAASi and/or MRA over the study period.","definition_or_measurement_approach":"Measure: proportion (%) of patients in each arm who discontinued RAASi and/or MRA during study."}
• {"endpoint_text":"- Number of patients achieving at least 50% of the target doses of RAASi since the screening visit (V0) to 1 month after study inclusion, considering the target dose of each RAASi drug recommended in the ESC guidelines","definition_or_measurement_approach":"Measure: count of patients achieving ≥50% of RAASi target doses at 1 month after inclusion compared to V0."}
• {"endpoint_text":"- Number of patients increasing 50% of RAASi doses since the screening visit (V0) to 1 month after study inclusion, considering the target dose of each RAASi drug recommended in the ESC guidelines","definition_or_measurement_approach":"Measure: count of patients with ≥50% increase in RAASi doses at 1 month after inclusion vs V0."}
• {"endpoint_text":"- 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).","definition_or_measurement_approach":"Measure: count of patients with ≥5% decrease in NT-proBNP from baseline (V1) to 3 months (V9)."}
• {"endpoint_text":"- Mean Change in NT-proBNP levels since the baseline visit (V1) to 3 months after study inclusion (V9).","definition_or_measurement_approach":"Measure: mean change in NT-proBNP from V1 to V9 (3 months)."}
• {"endpoint_text":"- 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).","definition_or_measurement_approach":"Measure: count of patients with ≥5% decrease in CA125 from V1 to V9 (3 months)."}
• {"endpoint_text":"- Mean Change in CA125 levels since the baseline visit (V1) to 3 months after study inclusion (V9).","definition_or_measurement_approach":"Measure: mean change in CA125 from V1 to V9 (3 months)."}
• {"endpoint_text":"- Mean change on Systolic arterial blood pressure measurement from baseline visit (V1) to 3 months after study inclusion (V9).","definition_or_measurement_approach":"Measure: mean change in systolic BP from V1 to V9 (3 months)."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Measure: mean change in KCCQ overall summary score from V1 to V9 (3 months) as a patient-reported outcome."}
• {"endpoint_text":"- To determine the change in renal function the following variables will be calculated between baseline visit (V1) and 3 months after study inclusion (V9): Mean Change in UACR and Mean change in HCO3","definition_or_measurement_approach":"Measure: mean change in UACR and HCO3 between V1 and V9 (3 months) to evaluate renal function changes."}
• {"endpoint_text":"- Number of patients decreasing at least 40% the eGFR since the screening visit (0) to 3 months after study inclusion (V9).","definition_or_measurement_approach":"Measure: count of patients with ≥40% decrease in eGFR (CKD-EPI) from V0 to V9 (3 months)."}
• {"endpoint_text":"- Mean change from baseline visit (V1) measured at 3 months after study inclusion (V9) (V9) in the overall summary score of KDQoL, as a specific CKD patient reported outcome questionnaire.","definition_or_measurement_approach":"Measure: mean change in KDQoL overall summary score from V1 to V9 (3 months)."}
• {"endpoint_text":"- Number of visits for HF/HK/impaired renal function/hypertension or hyperkalemia diagnosed in the outpatient clinic.","definition_or_measurement_approach":"Measure: count of outpatient visits for listed conditions during study period."}
• {"endpoint_text":"- Proportion of patients requiring hospitalization for HF/HK/impaired renal function over the study period.","definition_or_measurement_approach":"Measure: proportion (%) of patients hospitalized for HF/HK/renal impairment during study."}
• {"endpoint_text":"- Mean number of hospitalizations per patient for HF/HK/impaired renal function over the study period.","definition_or_measurement_approach":"Measure: mean hospitalizations per patient for listed conditions over study period."}
• {"endpoint_text":"- Proportion of patients presenting at least one clinical event over the study period","definition_or_measurement_approach":"Measure: proportion (%) of patients with ≥1 clinical event during study."}
• {"endpoint_text":"- Proportion of patients presenting more than one clinical event over the study period","definition_or_measurement_approach":"Measure: proportion (%) of patients with >1 clinical event during study."}
• {"endpoint_text":"- Proportion of patients presenting all clinical events over the study period","definition_or_measurement_approach":"Measure: proportion (%) of patients presenting the full set of predefined clinical events over study."}
• {"endpoint_text":"- Percentage of patients treated with and without sodium-glucose cotransporter-2 (SGLT2) inhibitors over the study period in both arms","definition_or_measurement_approach":"Measure: percentage of patients on SGLT2 inhibitors vs not during study in each arm."}
• {"endpoint_text":"- Mean Change in Mg levels since the baseline visit (V1) to 3 months after study inclusion (V9).","definition_or_measurement_approach":"Measure: mean change in magnesium levels from V1 to V9 (3 months)."}

Spain

Earliest CTIS Part Ii Submission Date

29-07-2024

Latest Decision Or Authorization Date

27-08-2025

Processing Time Days

394

Number Of Sites

6

Number Of Participants

94

Primary sponsor

Full Name

Hospital Clinico Universitario De Valencia

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Spain

Third parties

• {"country":"Spain","full_name":"Instituto De Investigacion Sanitaria Fundacion Para La Investigacion Del Hospital Clinico De Valencia-INCLIVA","duties_or_roles":"codes: 1,12,5,8","organisation_type":"Hospital/Clinic/Other health care facility"}