SENEKA: a randomized clinical trial to optimize RAASi therapy using sodium zirconium cyclosilicate in elderly patients with heart failure and chronic kidney disease at risk of hyperkalemia
C Bonanad Lozano, D Espinonsa, D Espinonsa, M P Lopez-Diez, M P Lopez-Diez, C Ortiz-Cortes, C Ortiz-Cortes, A Nogueron, A Nogueron, E Rodriguez Borja, E Rodriguez Borja, M Corbi, M Corbi, D Bompart, D Bompart, C Munoez-Alfonso, C Munoez-Alfonso, S Garcia-Blas, S Garcia-Blas, A Arroyo, A Arroyo, M Barreres Martin, M Barreres Martin, M Montomoli, M Montomoli, G Nunez-Marin, G Nunez-Marin, M Izquierdo, M IzquierdoAbstract
Background
Elderly patients with heart failure (HF) and chronic kidney disease (CKD) frequently experience hyperkalemia, a major barrier to achieving guideline-recommended doses of renin–angiotensin–aldosterone system inhibitors (RAASi), despite their proven prognostic benefits. Sodium zirconium cyclosilicate (SZC) effectively reduces and maintains normal serum potassium levels and may enable safer up-titration of RAASi therapy. The SENEKA trial aims to determine whether adding SZC facilitates RAASi optimization in this clinically vulnerable and traditionally underrepresented population.
Objective
To compare the proportion of patients achieving ≥25% increase in guideline-recommended target RAASi dose at 3 months between those treated with SZC + RAASi versus standard RAASi therapy without a potassium binder.
Methods
SENEKA is a multicentre, randomized, open-label, parallel-group trial conducted in Spain. Eligible patients are ≥70 years old, have HF (NYHA I–III) and CKD (eGFR <60 mL/min/1.73 m²), are stabilized after an HF decompensation, and present either mild hyperkalemia (5.1–5.9 mEq/L) or are at high risk of developing hyperkalemia (prior episode and K ≥4.5 mEq/L). After informed consent and eligibility confirmation, participants are randomized 1:1 to SZC or standard of care for 90 days, following a structured protocol for RAASi titration according to ESC guidelines. The sample size is 94 patients (47 per arm), providing 80% power to detect a difference of 30% vs 60% in the primary endpoint.
Secondary and exploratory endpoints include attainment of ≥50% of target RAASi or MRA dose, changes in NT-proBNP and CA125, blood pressure, renal function, magnesium, patient-reported outcomes (KCCQ and KDQoL), outpatient hyperkalemia events, emergency visits, hospitalizations for HF/hyperkalemia/renal impairment, and a composite clinical endpoint incorporating cardiovascular death and ≥40% decline in eGFR.
Safety assessments include monitoring of adverse events, severe hyper/hypokalemia, renal function, body weight, edema, and CA125 increases as a congestion-related composite endpoint. Strict discontinuation criteria apply for K >6.0 mEq/L, K <3.0 mEq/L, or significant QTc prolongation.
Expected Results:
It is anticipated that SZC will enable more patients to achieve meaningful RAASi up-titration without increasing adverse events related to potassium imbalance or congestion. Findings will inform the design of a future, larger, event-driven trial.
Conclusions
SENEKA is the first trial specifically designed for elderly HF + CKD patients immediately after hospitalization, evaluating SZC as an enabling strategy to optimize guideline-directed RAASi therapy. This approach has the potential to transform clinical practice and improve outcomes in a high-risk population.For image description, please refer to the figure legend and surrounding text.