Continuing Sodium Zirconium Cyclosilicate (SZC) After Discharge Study

NCT05347693 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: D9480C000232021-003527-14
• Study Type: interventional
• Target: 186
• Locations: 6 countries
• Sites: 28

Brief Summary

This is an open-label, randomised study in participants with chronic kidney disease (CKD) treated for hyperkalaemia (HK) whilst in hospital. The study will compare SZC to standard of care (SoC) with the goal of determining:

• If continued use of SZC maintains normokalaemia (NK) better than SoC after participant discharge from the hospital.
• If continued use of SZC after discharge will reduce HK related healthcare resource utilisation compared to SoC.

Conditions

Hyperkalaemia; Chronic Kidney Disease

Keywords

sodium zirconium cyclosilicate; Hyperkalaemia after discharge at the hospital

Outcome Measures

Primary Outcomes (1)

• Occurrence (Yes/No) of NK (K+ Between 3.5 and 5.0 mmol/L, Inclusive) at 180 Days Post-discharge

  A response was defined as a participant having serum K+ within 3.5 and 5.0 mmol/L at 180 days post-discharge. No response was defined as a participant who: 1) used rescue therapy for hyperkalaemia (HK) during the outpatient period; 1) died prior to 180 days post-discharge; 3) were missing an assessment at visit 10; 4) were lost to follow-up prior to 180 days post-discharge; 5) down-titrated (or discontinued) RAASi. The number of participants who had a response/no response is presented.

  At 180 days post-discharge (Visit 10)

Secondary Outcomes (6)

• Time to First Occurrence of Any Component of All-cause Hospital Admissions or ED Visits With HK as a Contributing Factor, or All-cause Death, or Use of Rescue Therapy for HK at Any Time Post-discharge up to 180 Days

  At any time post-discharge (from Visits 4 to 10), up to 180 days

• Time to First Occurrence of Any Component of All-cause Hospital Admission or ED Visit With HK as a Contributing Factor at Any Time Post-discharge up to 180 Days

  At any time post-discharge (from Visits 4 to 10), up to 180 days

• Number of All-cause Events (Hospital Admissions or ED Visits) With HK as a Contributing Factor at Any Time Post-discharge up to 180 Days

  At any time post-discharge (from Visits 4 to 10), up to 180 days

• Time to First Occurrence of RAASi Down-titration (or Discontinuation) at Any Time Post-discharge up to 180 Days

  At any time post-discharge (from Visits 4 to 10), up to 180 days

• Time to First Occurrence of Hospital Admission or ED Visit, Both With HK as a Contributing Factor at Any Time Post-discharge up to 180 Days

  At any time post-discharge (from Visits 4 to 10), up to 180 days

Study Arms (2)

Sodium Zirconium Cyclosilicate (SZC)

EXPERIMENTAL

Participants discharged with SZC, as per local label, to manage HK until the end of the outpatient phase

Drug: Sodium Zirconium Cyclosilicate (SZC)

Local standard of care (SoC)

ACTIVE COMPARATOR

Participants discharged with SoC, as per local practice, to manage HK until the end of study.

Drug: Local standard of care

Interventions

Sodium Zirconium Cyclosilicate (SZC) DRUG

White to grey crystalline powder for oral suspension in 5 g sachets. Each sachet will be labeled in accordance with Good Manufacturing Practice Annex 13 and per country regulatory requirement. Label text will be translated into local language.

Also known as: Lokelma

Sodium Zirconium Cyclosilicate (SZC)

Local standard of care DRUG

Local SoC in the country to be used as per local label

Also known as: SoC

Local standard of care (SoC)

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be 18 years of age or older, at the time of signing the informed consent
• Admitted to hospital (inpatient care; directly or from ED)
• With:
• Diagnosed CKD (any stage) or
• eGFR \< 90 ml/min/1.73 m2 at, or within 3 months of, study screening, based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (Levey et al, 2009).
• Note: Race/ethnicity should not be included in CKD-EPI equation calculation.
• Local laboratory K+ measurement within 24 hours of baseline visit (visit 2), where result is either:
• Hyperkalaemic as defined by site's local practice and K+ ≤ 6.5 mmol/L.
• Or, normokalaemic: K+ between ≥ 3.5 and ≤ 5.0 mmol/L, where patient started and is receiving treatment for this episode of HK
• Male or female
• Capable and willing of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

You may not qualify if:

• Hospitalisation for an acute cardiovascular event within 12 weeks prior to screening
• Unable to take oral SZC drug mix
• With a life expectancy of less than 6 months
• QT interval corrected by the Fridericia method (QTcF) \> 550 msec
• History of QT prolongation associated with other medications that required discontinuation of that medication
• Congenital long QT syndrome
• Clinically significant arrythmias as judged by the investigator
• Ongoing treatment with SZC or patiromer before current ED visit/hospital admission (ongoing treatment with other K-binders before current ED visit/hospital admission is allowed).
• Note: Initiation of any SZC or patiromer during the current ED visit/hospitalisation preceding enrolment is allowed.
• Chronic haemodialysis or peritoneal dialysis or the recipient of or scheduled date for a kidney transplant. Note: Emergency/unscheduled haemodialysis to treat HK during the current ED visit/hospitalisation preceding enrolment is allowed.
• Participation in another clinical study with an investigational medicinal product (IMP) administered during the month before screening.
• Known hypersensitivity to SZC or any of the excipients of the product
• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
• 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
• Previous randomisation in the present study

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (28)

Research Site

Bonheiden, 2820, Belgium

Location

Research Site

Leuven, 3000, Belgium

Location

Research Site

Annonay, 07103, France

Location

Research Site

Ars-Laquenexy, 57530, France

Location

Research Site

Nice, 06000, France

Location

Research Site

Saint-Priest-en-Jarez, 42270, France

Location

Research Site

Bari, 70120, Italy

Location

Research Site

Foggia, 71122, Italy

Location

Research Site

Parma, 43125, Italy

Location

Research Site

Pavia, 27100, Italy

Location

Research Site

Eindhoven, 5602 ZA, Netherlands

Location

Research Site

Algeciras, 11207, Spain

Location

Research Site

Almería, 04009, Spain

Location

Research Site

Badajoz, 06080, Spain

Location

Research Site

Barcelona, 08907, Spain

Location

Research Site

Burgos, 9006, Spain

Location

Research Site

Getafe, 28905, Spain

Location

Research Site

Madrid, 28007, Spain

Location

Research Site

Madrid, 28040, Spain

Location

Research Site

Salamanca, 37007, Spain

Location

Research Site

San Sebastián de los Reyes, 28702, Spain

Location

Research Site

Seville, 41009, Spain

Location

Research Site

Talavera de la Reina, 45600, Spain

Location

Research Site

Zamora, 49022, Spain

Location

Research Site

Doncaster, DN2 5LT, United Kingdom

Location

Research Site

Hull, HU10 7AZ, United Kingdom

Location

Research Site

Salford, M6 8HD, United Kingdom

Location

Research Site

Stevenage, SG1 4AB, United Kingdom

Location

Related Publications (1)

• Burton JO, Allum AM, Amin A, Linde C, Lesen E, Mellstrom C, Eudicone JM, Sood MM. Rationale and design of CONTINUITY: a Phase 4 randomized controlled trial of continued post-discharge sodium zirconium cyclosilicate treatment versus standard of care for hyperkalemia in chronic kidney disease. Clin Kidney J. 2023 Mar 23;16(7):1160-1169. doi: 10.1093/ckj/sfad053. eCollection 2023 Jul.

  PMID: 37398685 DERIVED

Related Links

• CSP redacted
• SAP redacted
• CSR Synopsis redacted

MeSH Terms

Conditions

Hyperkalemia; Renal Insufficiency, Chronic

Interventions

sodium zirconium cyclosilicate

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Results should be interpreted with great caution due to a high and imbalanced missingness of K+ results from the central laboratory at Day 180 / Visit 10 (51.5% in the SZC group and 36.2% in the SoC group). Hence, results are only described with no conclusive statement.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: No Masking
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a Phase 4, randomised, controlled, open-label, parallel-group, multicentre study in participants with CKD treated for HK whilst in hospital. * During the in-hospital phase, participants will be treated with SZC as per local label * At discharge, NK participants who have been treated with SZC for between 1 and 21 days whilst in hospital and are started on SZC maintenance dose will be randomised in a 1:1 ratio to one of the following arms: * Arm A: Participants discharged with SZC, as per local label, to manage HK until the end of the outpatient phase * Arm B: Participants discharged with SoC, as per local practice, to manage HK until the end of study. Note: Participants intended to be discharged with a K+ binder (as per the site routine medical practice) will not be randomised and will be discontinued from the study. * The total duration of the study for each participant will be up to approximately 6 months.

Study Record Dates

• First Submitted: February 23, 2022
• First Posted: April 26, 2022
• Study Start: March 24, 2022
• Primary Completion: December 10, 2024
• Study Completion: December 10, 2024
• Last Updated: November 28, 2025
• Results First Posted: November 28, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

BE (2); ES (13); FR (4); IT (4); GB (4); NL (1)