Lokelma (sodium zirconium cyclosilicate) / AstraZeneca - LARVOL DELTA

Sodium zirconium cyclosilicate for the management of hyperkalaemia in patients with heart failure with reduced ejection fraction - the REALIZE-K open-label run-in phase (HEART FAILURE 2025) - No abstract available

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure

The role of sodium zirconium cyclosilicate drug utilization in managing hyperkalemia: impact on healthcare resource utilization and on maintenance of renin-angiotensin-aldosterone system inhibitor therapy in Italian clinical practice. (PubMed, J Med Econ) - "This real-world study showed that nearly 17% of patients continued SZC therapy for ≥90 days. Long-term therapy was associated with lower RAASi discontinuation and reduced healthcare costs due to hospitalizations and outpatient specialist services, suggesting that SZC can potentially provide clinical and economic benefits for HK management."

HEOR • Journal • Retrospective data • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Heart Failure • Hypertension • Metabolic Disorders • Nephrology • Renal Disease

VITALIZE.Use and Effectiveness of Sodium Zirconium Cyclosilicate (LokelmaTM) in the Real-world Setting in Spain (clinicaltrials.gov) - P=N/A | N=233 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Real-world evidence

OPRA-HF: OPtimizing Aldosterone Receptor Antagonist Therapy by Sodium Zirconium Cyclosilicate in Heart Failure (clinicaltrials.gov) - P2 | N=110 | Active, not recruiting | Sponsor: Michael Fu | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2026 ➔ Jun 2026 | Trial primary completion date: Dec 2026 ➔ Dec 2025

Enrollment closed • Trial completion date • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure

THE JOURNEY OF BRASH AS NARRATED BY A PACEMAKER - Prutha R. Pathak (ACC 2025) - "Background: Bradycardia, renal insufficiency, AV nodal block, shock, and hyperkalemia (BRASH) causing pacemaker capture failure, i.e., the inability of a pacing impulse to produce an evoked potential, has rarely been described.Case: A 66-year-old woman with atrial fibrillation and sick sinus syndrome s/p dual-chamber pacemaker a month ago (on metoprolol succinate) and heart failure with preserved ejection fraction (on spironolactone, furosemide, and potassium chloride) presented with generalized weakness for 24 hours...Investigations demonstrated potassium of 9.4 mEq/dl, AKI (creatinine of 1 mg/dL from 0.6 at baseline), and capture failure on EKG.Decision-making: The patient was diagnosed with BRASH and resuscitated with intravenous fluids, norepinephrine, calcium gluconate, insulin, and sodium zirconium cyclosilicate. Recognizing BRASH as an important reversible cause of pacemaker capture failure and its immediate management is crucial in preventing cardiovascular..."

Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Dermatology • Heart Failure • Hypotension • Nephrology • Renal Disease

Updates in chronic kidney disease management: A systematic review. (PubMed, Pharmacotherapy) - "Currently, SGLT2i have demonstrated consistent benefits with large effect sizes in preventing the progression of CKD, solidifying this class as a first-line treatment along with RASi. Subsequent consideration for GLP-1RA, finerenone, and sacubitril/valsartan should be dependent on patient-specific comorbidities, while potassium binders may allow for longer use of RASi."

Journal • Review • Chronic Kidney Disease • Nephrology • Renal Disease

Post-marketing safety associated with sodium zirconium cyclosilicate: a pharmacovigilance study based on the FDA reporting system. (PubMed, Expert Opin Drug Saf) - "Furthermore, AEs differed between male and female patients. This study confirmed SZC label safety warnings and identified new AEs, offering insights for clinical monitoring of SZC."

Adverse events • Journal • P4 data • Cardiovascular • Congestive Heart Failure • Constipation • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Infectious Disease • Pneumonia • Respiratory Diseases

Safety assessment of sodium zirconium cyclosilicate: A FAERS-based disproportionality analysis. (PubMed, PLoS One) - "This study confirms common AEs of SZC and identifies new ones, highlighting the need for careful monitoring and facilitating its safe use in clinical settings. However, disproportionality analysis cannot formally prove causation and further studies are needed to confirm these associations."

Journal • Retrospective data • Cardiovascular • Congestive Heart Failure • Gastrointestinal Disorder • Heart Failure

Sodium zirconium cyclosilicate-associated adverse events: An analysis of the FAERS database. (PubMed, Int J Clin Pharmacol Ther) - "This study successfully identified and analyzed ADE signals from the FAERS database, contributing valuable insights for evaluating the rationality and safety of clinical medication practices involving SZC."

Adverse events • Journal

A Case of Sigmoid Colon Perforation Associated with Sodium Zirconium Cyclosilicate in a Patient with Advanced Rectal Cancer. (PubMed, Surg Case Rep) - "SZC is said to be associated with a lower risk of intestinal perforation compared with other similar drugs; however, in patients with certain conditions, such as intestinal obstruction or transit disorder resulting from malignant disease, adhesion, and inflammatory diseases, the accumulation of SZC in the intestinal lumen might increase the risk of perforation."

Journal • Colorectal Cancer • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Oncology • Pain • Primary Biliary Cholangitis • Rectal Cancer • Solid Tumor

Establishing Cross-Specialty Expert Consensus on the Optimal Management of Hyperkalemia in Patients With Heart Failure and Chronic Kidney Disease. (PubMed, Circ J) - "This consensus provides proposals that may help support the optimal management of RAASi-induced hyperkalemia in Japanese patients with HF and CKD. It highlights the importance of treating hyperkalemia alongside optimal RAASi therapy."

Journal • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease

Do Potassium Binders Block Both the Benefits and the Risks of Mineralocorticoid Receptor Antagonists in Heart Failure?: The Four Anti-Aldosterone Myths. (PubMed, J Am Coll Cardiol) - No abstract available

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

LIBRAL: Sodium Zirconium Cyclosilicate to Allow Liberal Fruit and Vegetable Intake for Patients with CKD Stage 3b and 4 (clinicaltrials.gov) - P4 | N=16 | Recruiting | Sponsor: Leiden University Medical Center | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Kidney Disease • Nephrology • Renal Disease

Radiopaque intestinal contents due to simultaneous ingestion of lanthanum carbonate and sodium zirconium cyclosilicate: a nephrology image. (PubMed, J Nephrol) - No abstract available

Journal • Nephrology

Non-inferiority of sodium zirconium cyclosilicate versus potassium-restricted diet in achieving normokalaemia in patients with type 2 diabetes mellitus: protocol for a multicentre, open-label, randomised controlled, two-arm clinical trial (SILVERSTAR study). (PubMed, BMJ Open) - "All data obtained from this study will be published in a peer-reviewed journal. jRCTs051230067."

Clinical protocol • Head-to-Head • Journal • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Comparison Among Potassium Binders on the Management of Hyperkalemia on Chronic Dialysis Patients: A Protocol for Systematic Review. (PubMed, G Ital Nefrol) - "The main aim is to evaluate the difference in serum potassium concentration after treatment with sodium zirconium cyclosilicate or patiromer compared to placebo/sodium polystyrene sulfonate/calcium polystyrene sulfonate. Conclusions. The present protocol for a systematic review will consider all existing evidence from published RCTs about the efficacy of HIF-PHIs on hemodialysis patients."

Journal • Renal Disease

EVALUATION OF SODIUM ZIRCONIUM CYCLOSILICATE FOR SULFAMETHOXAZOLE/TRIMETHOPRIM-INDUCED HYPERKALEMIA (SCCM 2025) - "SZC was efficacious at lowering elevated potassium in patients receiving SMX-TMP therapy without inducing hypokalemia. This suggests SZC may be considered in patients with treatment-limiting hyperkalemia due to SMX-TMP, especially when SMX-TMP is preferred therapy. To our knowledge, this is the first study evaluating SZC use due to SMX-TMP-induced hyperkalemia, and future studies are needed."

Chronic Kidney Disease • Infectious Disease • Nephrology • Pneumonia • Renal Disease • Respiratory Diseases

VITALIZE.Use and Effectiveness of Sodium Zirconium Cyclosilicate (LokelmaTM) in the Real-world Setting in Spain (clinicaltrials.gov) - P=N/A | N=230 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting | Trial completion date: Oct 2024 ➔ Apr 2025 | Trial primary completion date: Oct 2024 ➔ Apr 2025

Enrollment open • Real-world evidence • Trial completion date • Trial primary completion date

Effect of sodium zirconium cyclosilicate on hyperkalemia after parathyroidectomy in secondary hyperparathyroidism patients with maintenance hemodialysis: A randomized trial. (PubMed, Medicine (Baltimore)) - "SZC has the potential to reduce the occurrence of hyperkalemia and avoid urgent hemodialysis after PTX. We recommended that SZC could be used routinely in SHPT patients on the day of PTX surgery."

Clinical • Journal • Endocrine Disorders • Secondary Hyperparathyroidism

SZC Versus SPS for Treatment of Hyperkalemia in Hemodialysis Patients (clinicaltrials.gov) - P=N/A | N=120 | Completed | Sponsor: Alexandria University | Recruiting ➔ Completed | N=80 ➔ 120

Enrollment change • Trial completion • Renal Disease

SHIELD: A National, Multicenter, Prospective, Observational Study to Assess Patient Characteristics, Treatment Algorithms and Disease Management of Hyperkalaemia Patients With Chronic Kidney Disease or Under Dialysis or With Heart Failure, Treated With Sodium Zirconium Cyclosilicate in Greece (clinicaltrials.gov) - P=N/A | N=125 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease

Sodium zirconium cyclosilicate for MRAs optimization in HFrEF: lessons learned from the REALIZE-K trial. (PubMed, Heart Fail Rev) - "Patiromer and sodium zirconium cyclosilicate (SZC), two novel potassium binders, have emerged as highly effective and safe tools for managing hyperkalemia and enabling the optimization of MRA therapy. This mini-review critically examines the findings of the recently published REALIZE-K (Randomized Withdrawal Trial Evaluating Sodium Zirconium Cyclosilicate for the Management of Hyperkalemia in Patients With Symptomatic Heart Failure With Reduced Ejection Fraction and Receiving Spironolactone) trial, placing it within the broader context of current evidence on potassium binders and their potential role in mitigating hyperkalemia to optimize MRA treatment. Moreover, it explores other significant barriers to MRA optimization, including clinician concerns over the risk of hyperkalemia, a consistent and pervasive issue that often leads to treatment inertia. By addressing both physiological and psychological barriers, this review aims to provide a comprehensive understanding of..."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease

The role of cation-exchange resins in hyperkalemia management. (PubMed, Med J Armed Forces India) - "The management of hyperkalemia has evolved, incorporating calcium polystyrene sulfonate (CPS) and newer agents such as sodium zirconium cyclosilicate (SZC) and patiromer alongside traditional treatments. The findings suggest a shift toward newer potassium-binding agents in clinical practice, underscored by the need for individualized treatment approaches based on patient-specific factors. This article aims to guide clinicians in optimizing hyperkalemia management, ensuring effective, safe, and patient-centered care."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease

Severe acute kidney injury with suspected bilateral renal artery stenosis on renal Duplex while on concurrent ACE inhibition – A case for carbon dioxide renal angiography (ISN-WCN 2025) - "Lisinopril, Hydrochlorothiazide and Rosuvastatin were promptly discontinued...He also received 3 doses of oral sodium Zirconium cyclosilicate, 10 gm, repeated every 6 hours...He was started on Sevelamer carbonate, taken TID with meals, for hyperphosphatemia and was maintained on a renal diet...We posit that this was a clear medical indication for non-nephrotoxic carbon dioxide angiography. We plan to repeat the renal artery Duplex in the near future."

Clinical • Acute Kidney Injury • Cardiovascular • Cough • Dyslipidemia • Fatigue • Glomerulonephritis • Hematological Disorders • Hepatology • Human Immunodeficiency Virus • Hypertension • Infectious Disease • Inflammation • Metabolic Disorders • Nephrology • Pneumonia • Renal Disease • Respiratory Diseases • Thrombosis

MAXIMISATION OF RENIN-ANGIOTENSIN-ALDOSTERONE INHIBITORS IN HEART FAILURE PATIENTS WITH CKD USING POTASSIUM BINDER; PRELIMINARY ANALYSIS OF A RANDOMISED DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL (ISN-WCN 2025) - "Methods We conducted a double-blind placebo-controlled randomised trial to investigate the role of sodium zirconium cyclosilicate (SZC) in rapid maximisation of RAASi in HFrEF patients with CKD (eGFR5.5 mmol/L, with no statistical difference between the two groups (p=0.283). Table 1Baseline Characteristics Download: Download high-res image (190KB) Download: Download full-size image Figure 1 Download: Download high-res image (380KB) Download: Download full-size image Conclusions In this study of rapid RAASi maximisation, hyperkalaemia (>5.5 mmol/L) was more common in patients on placebo compared to SZC, however there was no statistically significant difference in proportion of patients who reached target dose of RAASi in CKD patients with HFrEF."

Clinical • Late-breaking abstract • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Coronary Artery Disease • Diabetic Nephropathy • Heart Failure • Nephrology