Effect of Sodium Zirconium Cyclosilicate on Arrythmia-related Cardiovascular Outcomes in Participants on Chronic Hemodialysis With Recurrent Hyperkalemia (DIALIZE-Outcomes)

Inclusion Criteria:

1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol
2. Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses
3. Must be ≥ 18 years of age, at the time of signing the ICF.
4. Receiving hemodialysis (or hemodiafiltration) 3 times a week for treatment of ESRD for ≥ 4 months before enrollment
5. Must have hemodialysis access consisting of an arteriovenous fistula, arteriovenous graft, or tunneled (permanent) catheter which is expected to remain in place for the entire duration of the study
6. At least 2 out of 3 pre-dialysis S K ≥ 5.5 mmol/L after the LIDI during screening
7. Negative pregnancy test for female participants of childbearing potential
8. Female participants must be 1 year postmenopausal, surgically sterile, or using one highly effective form of birth control (defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly). They should have been stable on their chosen method of birth control for a minimum of 3 months before entering the study and willing to remain on the birth control until 12 weeks after the last dose

Exclusion Criteria:

1. Pseudohyperkalemia secondary to hemolyzed blood specimen (this situation is not considered screening failure, sampling or full screening can be postponed to a later time as applicable)
2. Presence of cardiac arrhythmias or conduction defects that require immediate treatment
3. Participants who have a pacemaker or implantable cardiac defibrillator
4. Any medical condition, including active, clinically significant infection or liver disease, that in the opinion of the investigator or sponsor may pose a safety risk to a participant in this study, confound safety or efficacy assessment and jeopardize the quality of the data, or interfere with study participation, or any other restrictions or contraindications in the local prescribing information for SZC
5. History of QT prolongation associated with other medications that required discontinuation of that medication
6. Congenital long QT syndrome
7. QTcF > 550 msec
8. Atrial fibrillation requiring immediate/urgent intervention at screening or randomizations
9. Treated with sodium polystyrene sulfonate (SPS, Kayexalate, Resonium), calcium polystyrene sulfonate (CPS Resonium Calcium), patiromer (Veltassa), or SZC (Lokelma) within 7 days before screening or anticipated requiring chronic use of any of these agents during the study. If participant requires rescue therapy (potassium binder or dialysate S-K change during screening period), the participant will be screen failed
10. Participation in another clinical study with an investigational product, device, or non-standard hemodialysis procedure administered within one month before screening
11. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
12. Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements
13. Previous randomization in the present study
14. Females who are pregnant (confirmed with positive pregnancy test or a uterine ultrasound if pregnancy test result is questionable), breastfeeding, or planning to become pregnant during the study
15. Known hypersensitivity or previous anaphylaxis to SZC or to components thereof
16. Scheduled date for living donor kidney transplant
17. Sustained Ventricular Tachycardia > 30 seconds requiring assessment / intervention