Continuing Sodium Zirconium Cyclosilicate (SZC) After Dis... | NCT05347693

ID	Type	Description	Link
2021-003527-14	EudraCT Number

Description Module

Detailed Description

This is a Phase 4, randomised, controlled, open-label, parallel-group, multicentre study in participants with CKD treated for HK whilst in hospital.

Participants from 30 to 50 sites in 4 to 7 countries will be screened for enrolment. In total, up to a maximum of 163 participants will be enrolled, resulting in approximately 130 participants discharged and randomised and 104 evaluable participants (52 per arm).
The study plans to enrol approximately equal numbers of participants with mild HK (K+ between > 5.0 and ≤ 5.5 mmol/L) and with moderate/severe HK (K+ between > 5.5 and ≤ 6.5 mmol/L), with a minimum of 30% of the enrolled participants in either group.
During the in-hospital phase, participants will be treated with SZC as per local label, starting at baseline and based on local K+ measurement obtained within 24 hours of treatment initiation:).
- Participants with HK (K+ between > 5.0 and ≤ 6.5 mmol/L):
  1. stop current K-binder if any
  2. start SZC correction dose (note: participants currently on SZC should continue SZC correction dose, up to 72 hours).
- Participants currently receiving any treatment for the current episode of HK and are already NK at baseline (K+ ≤ 5.0 mmol/L): 1) stop any current K-binder, 2) start SZC maintenance dose (note: participants currently on SZC maintenance dose should continue SZC maintenance dose).
- All treatment decisions, including modification of the ongoing therapy for HK must be based on the investigator's medical judgement of the participant's best interest.
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. Still, participants randomised into Arm B may have a K-binder prescribed at Day 7 post-discharge, (or after Day 7 post-discharge), to treat confirmed HK or in case there is an increase in K+ level since discharge that, in the investigator's opinion, requires therapy.
The total duration of the study for each participant will be up to approximately 6 months.
Study visit schedule is as follows:

In-hospital phase: - The screening visit will occur while the participant is at the hospital (up to 21 days before discharge; medical monitor's approval may be sought for allowing longer duration hospital stays for specific participants) in order to check eligibility criteria

Inpatient phase: o The baseline visit (can occur the same day as the screening visit) where treatment with SZC will be initiated

o The discharge visit, 1 to 20 days after baseline; medical monitor's approval may be sought for allowing longer duration hospital stays for specific participants). Randomisation will occur at day of discharge.
Outpatient phase: - Visits will occur at 7, 30, 60, 90, 120, 150, and 180 (EOT, End of Trial) days after randomisation. Only visits at 7, 90 and 180 days after randomisation will be on-site visits, the remaining being telephone visits. If dose titration occurs at any time during the outpatient phase, unscheduled dispensation visits will be performed.

Follow-up phase: - A follow-up on-site visit (end of study visit) will occur approximately 7 days after EOT. • Data will be collected at on-site visits, via telephone visits and medical chart reviews.

• An adjudication committee will be involved in the study.

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
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.

Measure	Description	Time Frame
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)

Measure	Description	Time Frame
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	The time to first occurrence of all-cause hospital admission, emergency department (ED) visits with HK as a contributing factor, all-cause death or use of rescue therapy for HK was calculated as date of first occurrence of (all-cause hospital admission, ED visits with HK as a contributing factor, all-cause death, use of rescue therapy for HK, date of loss to follow-up) - date of randomization + 1. The median time to event (days) is presented.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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:
1. Diagnosed CKD (any stage) or
2. 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.

Exclusion Criteria:

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
Any medical condition that, in the opinion of the investigator makes the participant not suitable for inclusion
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
For women only: Women of child-bearing potential (WOCBP; ie, those who are not chemically or surgically sterilised or who are not post-menopausal) who are not willing to use one of the methods of contraception described hereafter, or who are not stable on the contraception method for the last one month, from the time of signing the informed consent throughout the study and 7 days after the last dose: (a) Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal (b) Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable (c) Intrauterine device (d) Intrauterine hormone-releasing system (e) Bilateral tubal occlusion (f) Vasectomised partner (vasectomised partner is a highly effective birth control method provided that partner is the sole sexual partner of the WOCBP participant and that the vasectomised partner has received medical assessment of the surgical success (g) Sexual abstinence: it is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant.
For WOCBP only: Women who have a positive pregnancy test at screening OR women who are breastfeeding.

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Bonheiden		2820	Belgium
Research Site

PubMed Identifier	Type	Citation	Retractions
37398685	Derived	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.

Label	URL
CSP redacted	View source

ID	Title	Description
FG000	Inpatient Period	Participants were treated with SZC as per local label (correction and/or maintenance treatment), starting at baseline and based on local potassium (K+) measurement obtained within 24 hours of treatment initiation.
FG001	Outpatient Period - Arm A: SZC

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 2, 2023	Oct 14, 2025

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Full Analysis Set (FAS). The FAS included all randomised participants.

Posted

Number

Number of participants

At 180 days post-discharge (Visit 10)

ID	Title	Description
OG000	Arm A: SZC	Participants discharged with SZC, as per local label, to manage HK until 7 days before the end of the study.
OG001	Arm B: SoC	SZC was withdrawn and participants discharged with SoC, as per local practice, to manage HK until the end of study.

Units	Counts
Participants	OG00068 OG00169

Title

Denominators

Categories

Response

Title	Measurements
	OG00021 OG00125

No response

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Regression, Logistic	Model included response as the dependent variable, and randomised treatment and participant recruitment country as independent factors.	0.558		Odds Ratio (OR)	0.81			2-Sided	95	0.39	1.66			OR >1 indicated increased odds of K+ between 3.5 and 5.0 mmol/L on SZC compared to SoC.		Equivalence	Prespecified estimates for sample size calculation Equivalence margin: 0.29 Sample size estimate parameters: Two-group χ² test Significance level (α): 5% (two-sided) Power: 80% Assumed proportions with NK (K+ between 3.5 and 5.0 mmol/L, inclusive) at 180 days post-discharge: Arm A: 0.88 Arm B: 0.59 Note: Assumed proportions for statistical planning; not actual results.

Secondary

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

The time to first occurrence of all-cause hospital admission, emergency department (ED) visits with HK as a contributing factor, all-cause death or use of rescue therapy for HK was calculated as date of first occurrence of (all-cause hospital admission, ED visits with HK as a contributing factor, all-cause death, use of rescue therapy for HK, date of loss to follow-up) - date of randomization + 1.

The median time to event (days) is presented.

FAS. The FAS included all randomised participants.

Posted

Median

95% Confidence Interval

Days

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

ID	Title	Description
OG000	Arm A: SZC	Participants discharged with SZC, as per local label, to manage HK until 7 days before the end of the study.
OG001	Arm B: SoC	SZC was withdrawn and participants discharged with SoC, as per local practice, to manage HK until the end of study.

Units	Counts

Secondary

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

The 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 was calculated as the earliest date of (all-cause hospital admission, ED visits with HK as a contributing factor, all-cause death, use of rescue therapy for HK, date of loss to follow-up, date of 180 days post-discharge) - date of randomization + 1.

The median time to event (days) is presented.

FAS. The FAS included all randomised participants.

Posted

Median

95% Confidence Interval

Days

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

ID	Title	Description
OG000	Arm A: SZC	Participants discharged with SZC, as per local label, to manage HK until 7 days before the end of the study.
OG001	Arm B: SoC	SZC was withdrawn and participants discharged with SoC, as per local practice, to manage HK until the end of study.

Units	Counts
Participants

Secondary

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

The 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 is presented.

Participants who discontinued treatment, used rescue therapy for HK, experienced all-cause death or loss to follow-up prior to 180 days post-discharge or who down-titrated (including discontinued) RAASi were to have all available hospital admission data used irrespective of the intercurrent event (treatment policy strategy).

FAS. The FAS included all randomised participants.

Posted

Mean

Standard Deviation

Events

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

ID	Title	Description
OG000	Arm A: SZC	Participants discharged with SZC, as per local label, to manage HK until 7 days before the end of the study.
OG001	Arm B: SoC	SZC was withdrawn and participants discharged with SoC, as per local practice, to manage HK until the end of study.

Units	Counts
Participants

Secondary

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

The time to first occurrence of RAASi down-titration (or discontinuation) was calculated as date of first occurrence of (RAASi down-titration, all-cause death, date of loss to follow-up) - date of randomization + 1.

The median time to event (days) is presented.

FAS. The FAS included all randomised participants.

Posted

Median

95% Confidence Interval

Days

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

ID	Title	Description
OG000	Arm A: SZC	Participants discharged with SZC, as per local label, to manage HK until 7 days before the end of the study.
OG001	Arm B: SoC	SZC was withdrawn and participants discharged with SoC, as per local practice, to manage HK until the end of study.

Units	Counts
Participants	OG000

Secondary

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

The time to first occurrence of hospital admission or ED visit, both with HK as a contributing factor, was calculated as date of first occurrence of (Hospital admission or ED visit with HK as a contributing factor, all-cause death, use of rescue therapy for HK, date of loss to follow-up) - date of randomization + 1.

The median time to event (days) is presented.

FAS. The FAS included all randomised participants.

Posted

Median

95% Confidence Interval

Days

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

ID	Title	Description
OG000	Arm A: SZC	Participants discharged with SZC, as per local label, to manage HK until 7 days before the end of the study.
OG001	Arm B: SoC	SZC was withdrawn and participants discharged with SoC, as per local practice, to manage HK until the end of study.

Units	Counts
Participants

Secondary

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

The number of events (hospital admissions or ED visits) with HK as a contributing factor, at any time post-discharge up to 180 days is presented.

Participants who discontinued treatment, used rescue therapy for HK, experienced all-cause death or loss to follow-up prior to 180 days post-discharge or who downtitrated (including discontinued) RAASi were to have all available hospital admission data used irrespective of the intercurrent event (treatment policy strategy).

FAS. The FAS included all randomised participants.

Posted

Mean

Standard Deviation

Events

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

ID	Title	Description
OG000	Arm A: SZC	Participants discharged with SZC, as per local label, to manage HK until 7 days before the end of the study.
OG001	Arm B: SoC	SZC was withdrawn and participants discharged with SoC, as per local practice, to manage HK until the end of study.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0020 events0 affected68 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0010 events0 affected68 at risk EG0021 events1 affected68 at risk
Gastric perforation	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0020 events0 affected68 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0020 events0 affected68 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0020 events0 affected68 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0010 events0 affected68 at risk EG0021 events1 affected68 at risk
Oedema	General disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0020 events0 affected68 at risk
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0020 events0 affected68 at risk
Bronchitis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0020 events0 affected68 at risk
Covid-19	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0010 events0 affected68 at risk EG0021 events1 affected68 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected174 at risk EG0012 events1 affected68 at risk EG0022 events1 affected68 at risk
Covid-19 pneumonia	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0010 events0 affected68 at risk EG0021 events1 affected68 at risk
Erysipelas	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0020 events0 affected68 at risk
Gastroenteritis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0020 events0 affected68 at risk
Influenza	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0010 events0 affected68 at risk EG0021 events1 affected68 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0010 events0 affected68 at risk EG0021 events1 affected68 at risk
Penile abscess	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0010 events0 affected68 at risk EG0021 events1 affected68 at risk
Pneumonia	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0014 events3 affected68 at risk EG0021 events1 affected68 at risk
Pneumonia aspiration	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0020 events0 affected68 at risk
Sepsis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected174 at risk EG0010 events0 affected68 at risk EG0021 events1 affected68 at risk
Septic shock	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0020 events0 affected68 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0010 events0 affected68 at risk EG0021 events1 affected68 at risk
Subcutaneous abscess	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0010 events0 affected68 at risk EG0021 events1 affected68 at risk
Urinary tract infection	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0012 events2 affected68 at risk EG0021 events1 affected68 at risk
Urosepsis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0010 events0 affected68 at risk EG0021 events1 affected68 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0020 events0 affected68 at risk
Vascular pseudoaneurysm	Injury, poisoning and procedural complications	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0010 events0 affected68 at risk EG0021 events1 affected68 at risk
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0020 events0 affected68 at risk
Electrocardiogram qt prolonged	Investigations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0010 events0 affected68 at risk EG0021 events1 affected68 at risk
Diabetic metabolic decompensation	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0010 events0 affected68 at risk EG0021 events1 affected68 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0020 events0 affected68 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0010 events0 affected68 at risk EG0021 events1 affected68 at risk
Cardiac arrest	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0020 events0 affected68 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0022 events2 affected68 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0010 events0 affected68 at risk EG0021 events1 affected68 at risk
Epilepsy	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0010 events0 affected68 at risk EG0021 events1 affected68 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0020 events0 affected68 at risk
Myasthenia gravis crisis	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0020 events0 affected68 at risk
Confusional state	Psychiatric disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0020 events0 affected68 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0013 events3 affected68 at risk EG0022 events1 affected68 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0022 events2 affected68 at risk
Cardiac failure	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected174 at risk EG0015 events2 affected68 at risk EG0023 events2 affected68 at risk
Male genital tract fistula	Reproductive system and breast disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0010 events0 affected68 at risk EG0021 events1 affected68 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0012 events2 affected68 at risk EG0020 events0 affected68 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0020 events0 affected68 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0010 events0 affected68 at risk EG0021 events1 affected68 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0021 events1 affected68 at risk
Hypotension	Vascular disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0010 events0 affected68 at risk EG0021 events1 affected68 at risk
Ischaemia	Vascular disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0020 events0 affected68 at risk
Peripheral ischaemia	Vascular disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0020 events0 affected68 at risk
Cardiac failure chronic	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0012 events1 affected68 at risk EG0020 events0 affected68 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0010 events0 affected68 at risk EG0021 events1 affected68 at risk
Cardiac tamponade	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0010 events0 affected68 at risk EG0021 events1 affected68 at risk
Pericarditis	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected68 at risk EG0020 events0 affected68 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected174 at risk EG0010 events0 affected68 at risk EG0020 events0 affected68 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected174 at risk EG0010 events0 affected68 at risk EG0020 events0 affected68 at risk
Intestinal ischaemia	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected174 at risk EG0010 events0 affected68 at risk EG0020 events0 affected68 at risk
Postoperative wound infection	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected174 at risk EG0010 events0 affected68 at risk EG0020 events0 affected68 at risk
Penile squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected174 at risk EG0010 events0 affected68 at risk EG0020 events0 affected68 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected174 at risk EG0010 events0 affected68 at risk EG0020 events0 affected68 at risk
Renal impairment	Renal and urinary disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected174 at risk EG0010 events0 affected68 at risk EG0020 events0 affected68 at risk
Medical device site haemorrhage	General disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected174 at risk EG0010 events0 affected68 at risk EG0020 events0 affected68 at risk

ID	Term
D006947	Hyperkalemia
D051436	Renal Insufficiency, Chronic

ID	Term
D014883	Water-Electrolyte Imbalance
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D051437	Renal Insufficiency
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Title	Description
BG000	Outpatient Period - Arm A: SZC	Participants discharged with SZC, as per local label, to manage HK until 7 days before the end of the study.
BG001	Outpatient Period - Arm B: SoC	SZC was withdrawn and participants discharged with SoC, as per local practice, to manage HK until the end of study.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Inpatient Period	Participants were treated with SZC as per local label (correction and/or maintenance treatment), starting at baseline and based on local K+ measurement obtained within 24 hours of treatment initiation.	2	174	10	174	0	174
EG001	Outpatient Period - Arm A: SZC	Participants discharged with SZC, as per local label, to manage HK until 7 days before the end of the study.	6	68	29	68	22	68
EG002	Outpatient Period - Arm B: SoC	SZC was withdrawn and participants discharged with SoC, as per local practice, to manage HK until the end of study.	2	68	21	68	30	68