A Phase 3 interventional study of Sodium Zirconium Cyclosilicate (SZC) and SZC Placebo in Hyperkalemia, sponsored by AstraZeneca. Terminated at 340 sites in 26 countries. Open to participants aged 18 Years to 130 Years. Per ClinicalTrials.gov, last updated 2025-06-18.
Sponsored by AstraZeneca · Phase 3, Interventional, and Treatment
The purpose of this study is to evaluate the effect of Sodium Zirconium Cyclosilicate (SZC) on arrhythmia-related cardiovascular outcomes in participants on chronic hemodialysis with recurrent hyperkalemia.
This is an international, multicenter, event-driven, randomized, double-blind, parallel group, placebo-controlled study, evaluating the utility of SZC versus placebo to reduce the incidence of sudden cardiac death (SCD), stroke, and arrhythmia-related hospitalizations, interventions, and emergency department (ED) visits in participants on chronic hemodialysis with recurrent hyperkalemia.
Exclusion Criteria:
Drug: Sodium Zirconium Cyclosilicate (SZC)
Drug: SZC Placebo
Powder for oral suspension in a sachet. A dose is titrated in 5 g increments during a period of 4 weeks from 5 g up to 15 g qd on non-dialysis days. Afterward, the dose is adjusted monthly (or more frequent based on clinical judgment) depending on the current potassium value as measured after the long interdialytic interval (LIDI).
Also known as: Lokelma TM
Powder for oral suspension in a sachet. A dose is titrated in 5 g increments during a period of 4 weeks from 5 g up to 15 g qd on non-dialysis days. Afterward, the dose is adjusted monthly (or more frequent based on clinical judgment) depending on the current potassium value as measured after the LIDI.
Incidence of the Composite of Cardiac Event Outcomes
Incidence of the composite endpoint of SCD, all stroke, or hospitalization/intervention/emergency department (ED) visit due to arrhythmias is analyzed based on Cox regression model with treatment and region as covariates. Patients with no events are censored at final clinical assessment, death, or disposition event.
Time frame: From Randomization (Visit 4) up to week 129 (Randomized Study Intervention Phase)
Normokalemia at 12 Months Post-randomization
Logistic regression analysis of whether a subject is Normokalemic (S-K of 4.0 - 5.5 mmol/L ) after the LIDI at the 12-month visit.
Time frame: Randomization to 12-Month Visit
Incidence of the Composite of Arrhythmia Related Events
Incidence of the composite endpoint of hospitalization, intervention, emergency department (ED) visit due to arrhythmias is analyzed based on Cox regression model with treatment and region as covariates. Patients with no events are censored at final clinical assessment, death, or disposition event.
Time frame: From Randomization (Visit 4) up to week 129 (Randomized Study Intervention Phase)
| Milestone | SZC (Active) | Placebo |
|---|---|---|
| Started | 1349 | 1341 |
| Completed | 0 | 0 |
| Not completed | 1349 | 1341 |
| Withdrew: Death | 123 | 115 |
| Withdrew: Lost to follow-up | 3 | 10 |
| Withdrew: Withdrawal by subject | 73 | 101 |
| Withdrew: Subcategories under "other" not reported. | 1150 | 1115 |
Incidence of the composite endpoint of SCD, all stroke, or hospitalization/intervention/emergency department (ED) visit due to arrhythmias is analyzed based on Cox regression model with treatment and region as covariates. Patients with no events are censored at final clinical assessment, death, or disposition event.
| Participants | SZC (Active) | Placebo |
|---|---|---|
| Incidence of the Composite of Cardiac Event Outcomes | 119 | 119 |
Logistic regression analysis of whether a subject is Normokalemic (S-K of 4.0 - 5.5 mmol/L ) after the LIDI at the 12-month visit.
| Participants with event | SZC (Active) | Placebo |
|---|---|---|
| Normokalemia at 12 Months Post-randomization | 495 | 293 |
Incidence of the composite endpoint of hospitalization, intervention, emergency department (ED) visit due to arrhythmias is analyzed based on Cox regression model with treatment and region as covariates. Patients with no events are censored at final clinical assessment, death, or disposition event.
| Participants | SZC (Active) | Placebo |
|---|---|---|
| Incidence of the Composite of Arrhythmia Related Events | 74 | 65 |
Collected over From Randomization (Visit 4) up to week 129 (Randomized Study Intervention Phase). Non-serious events are listed at a 3% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| SZC (Active) | 120/1,348 (8.9%) | 521/1,348 (38.6%) | 558/1,348 (41.4%) |
| Placebo | 113/1,338 (8.4%) | 503/1,338 (37.6%) | 616/1,338 (46%) |
| Event | SZC (Active) | Placebo |
|---|---|---|
| PneumoniaInfections and infestations | 61/1348 | 60/1338 |
| HyperkalaemiaMetabolism and nutrition disorders | 15/1348 | 39/1338 |
| SepsisInfections and infestations | 36/1348 | 20/1338 |
| Acute myocardial infarctionCardiac disorders | 26/1348 | 19/1338 |
| HypervolaemiaMetabolism and nutrition disorders | 22/1348 | 16/1338 |
| Arteriovenous fistula thrombosisInjury, poisoning and procedural complications | 16/1348 | 21/1338 |
| Covid-19 pneumoniaInfections and infestations | 21/1348 | 20/1338 |
| Covid-19Infections and infestations | 19/1348 | 16/1338 |
| Arteriovenous fistula site complicationInjury, poisoning and procedural complications | 11/1348 | 17/1338 |
| DeathGeneral disorders | 15/1348 | 12/1338 |
| Event | SZC (Active) | Placebo |
|---|---|---|
| HyperkalaemiaMetabolism and nutrition disorders | 125/1348 | 280/1338 |
| Covid-19Infections and infestations | 145/1348 | 122/1338 |
| DiarrhoeaGastrointestinal disorders | 98/1348 | 93/1338 |
| HypertensionVascular disorders | 80/1348 | 82/1338 |
| ConstipationGastrointestinal disorders | 76/1348 | 57/1338 |
| AnaemiaBlood and lymphatic system disorders | 64/1348 | 44/1338 |
| NauseaGastrointestinal disorders | 43/1348 | 59/1338 |
| Dialysis hypotensionVascular disorders | 55/1348 | 59/1338 |
| VomitingGastrointestinal disorders | 44/1348 | 54/1338 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 49/1348 | 54/1338 |
| Age, Continuous(Years) | SZC (Active) | Placebo | Total |
|---|---|---|---|
| Mean | 55.8 ± 13.3 | 56.3 ± 13.6 | 56.1 ± 13.4 |
| Age, Customized(Participants) | SZC (Active) | Placebo | Total |
|---|---|---|---|
| 18 yr ≤ Age < 51 yr | 442 | 441 | 883 |
| 51 yr ≤ Age < 65 yr | 526 | 509 | 1035 |
| 65 yr ≤ Age < 85 yr | 373 | 378 | 751 |
| Age ≥ 85 yr | 8 | 13 | 21 |
| Sex: Female, Male(Participants) | SZC (Active) | Placebo | Total |
|---|---|---|---|
| Female | 498 | 517 | 1015 |
| Male | 851 | 824 | 1675 |
| Race/Ethnicity, Customized(Participants) | SZC (Active) | Placebo | Total |
|---|---|---|---|
| AMERICAN INDIAN OR ALASKA NATIVE | 49 | 52 | 101 |
| ASIAN | 392 | 389 | 781 |
| BLACK OR AFRICAN AMERICAN | 121 | 130 | 251 |
| NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER | 3 | 2 | 5 |
| WHITE | 688 | 672 | 1360 |
| OTHER | 75 | 86 | 161 |
| NOT REPORTED | 21 | 10 | 31 |
| spKt/V(Dimensionless) | SZC (Active) | Placebo | Total |
|---|---|---|---|
| Mean | 1.48 ± 0.39 | 1.51 ± 0.47 | 1.49 ± 0.43 |
| Dialysis vintage(Years) | SZC (Active) | Placebo | Total |
|---|---|---|---|
| Mean | 6.01 ± 5.41 | 5.82 ± 5.20 | 5.92 ± 5.31 |
Showing the first 100 of 340 sites across 26 countries.
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Supporting information: Study protocol, Sap
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