Hyperkalaemia, Chronic Kidney Disease
Conditions
Keywords
sodium zirconium cyclosilicate, Hyperkalaemia after discharge at the hospital
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.
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.
Interventions
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.
Local SoC in the country to be used as per local label
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
No Masking
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence (Yes/No) of NK (K+ Between 3.5 and 5.0 mmol/L, Inclusive) at 180 Days Post-discharge | At 180 days post-discharge (Visit 10) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| 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 | 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). |
| 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 | 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. |
| 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 | 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. |
| Number of 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 | 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). |
| 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 | 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. |
Countries
Belgium, France, Italy, Netherlands, Spain, United Kingdom
Participant flow
Recruitment details
A total of 186 participants were screened from 28 study sites across 6 countries.
Pre-assignment details
This study consisted of 2 phases: an inpatient period and an outpatient period. Of the 186 participants enrolled in the inpatient period, 137 participants were randomized into the outpatient period (68 to Arm A and 69 to Arm B). The remaining 49 participants were not randomized due to reasons such as withdrawal of consent, failure to meet inclusion/exclusion criteria, screening failure, death, or other reasons (eg, mistaken study termination or discharged without notifying investigators).
Participants by arm
| Arm | Count |
|---|---|
| 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. | 68 |
| 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. | 68 |
| Total | 136 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Inpatient Period | Adverse Event | 3 | 0 | 0 |
| Inpatient Period | Death | 2 | 0 | 0 |
| Inpatient Period | Failure to meet inclusion/exclusion criteria | 19 | 0 | 0 |
| Inpatient Period | Participant was discharged from the hospital but did not inform the site | 1 | 0 | 0 |
| Inpatient Period | Physician Decision | 5 | 0 | 0 |
| Inpatient Period | Screening Failure | 8 | 0 | 0 |
| Inpatient Period | Withdrawal of consent | 10 | 0 | 0 |
| Inpatient Period | Withdrawn from study due to a mistaken request for study termination | 1 | 0 | 0 |
| Outpatient Period | Adverse Event | 0 | 9 | 0 |
| Outpatient Period | Death | 0 | 6 | 2 |
| Outpatient Period | Development of study-specific withdrawal criteria: Severe HK | 0 | 0 | 1 |
| Outpatient Period | Lost to Follow-up | 0 | 0 | 1 |
| Outpatient Period | Participant's study compliance was impossible to monitor and they had a complex private situation. | 0 | 1 | 0 |
| Outpatient Period | Scheduled hemodialysis | 0 | 1 | 0 |
| Outpatient Period | Severe HK | 0 | 0 | 1 |
| Outpatient Period | Started dialysis on 16 Feb 2023 | 0 | 1 | 0 |
| Outpatient Period | Start of dialysis | 0 | 0 | 1 |
| Outpatient Period | The participant entered hemodialysis | 0 | 0 | 1 |
| Outpatient Period | The participant moved to another city and could not attend the study visits | 0 | 0 | 1 |
| Outpatient Period | Withdrawal by Subject | 0 | 8 | 5 |
Baseline characteristics
| Characteristic | Outpatient Period - Arm A: SZC | Outpatient Period - Arm B: SoC | Total |
|---|---|---|---|
| Age, Continuous | 72.8 Years STANDARD_DEVIATION 10.25 | 72.1 Years STANDARD_DEVIATION 10.99 | 72.5 Years STANDARD_DEVIATION 10.59 |
| Age, Customized 18-64 years | 14 Participants | 13 Participants | 27 Participants |
| Age, Customized 65-84 years | 45 Participants | 47 Participants | 92 Participants |
| Age, Customized >=85 years | 9 Participants | 8 Participants | 17 Participants |
| Country Belgium | 0 Participants | 2 Participants | 2 Participants |
| Country France | 4 Participants | 2 Participants | 6 Participants |
| Country Italy | 6 Participants | 3 Participants | 9 Participants |
| Country Netherlands | 1 Participants | 0 Participants | 1 Participants |
| Country Spain | 57 Participants | 59 Participants | 116 Participants |
| Country United Kingdom | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 21 Participants | 10 Participants | 31 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 43 Participants | 56 Participants | 99 Participants |
| Race/Ethnicity, Customized Not Reported | 4 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 64 Participants | 64 Participants | 128 Participants |
| Sex: Female, Male Female | 25 Participants | 16 Participants | 41 Participants |
| Sex: Female, Male Male | 43 Participants | 52 Participants | 95 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 174 | 6 / 68 | 2 / 68 |
| other Total, other adverse events | 0 / 174 | 22 / 68 | 30 / 68 |
| serious Total, serious adverse events | 10 / 174 | 29 / 68 | 21 / 68 |
Outcome results
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.
Time frame: At 180 days post-discharge (Visit 10)
Population: Full Analysis Set (FAS). The FAS included all randomised participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A: SZC | Occurrence (Yes/No) of NK (K+ Between 3.5 and 5.0 mmol/L, Inclusive) at 180 Days Post-discharge | Response | 21 Number of participants |
| Arm A: SZC | Occurrence (Yes/No) of NK (K+ Between 3.5 and 5.0 mmol/L, Inclusive) at 180 Days Post-discharge | No response | 47 Number of participants |
| Arm B: SoC | Occurrence (Yes/No) of NK (K+ Between 3.5 and 5.0 mmol/L, Inclusive) at 180 Days Post-discharge | Response | 25 Number of participants |
| Arm B: SoC | Occurrence (Yes/No) of NK (K+ Between 3.5 and 5.0 mmol/L, Inclusive) at 180 Days Post-discharge | No response | 44 Number of participants |
p-value: 0.55895% CI: [0.39, 1.66]Regression, Logistic
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).
Time frame: At any time post-discharge (from Visits 4 to 10), up to 180 days
Population: FAS. The FAS included all randomised participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: SZC | 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 | 0.7 Events | Standard Deviation 0.92 |
| Arm B: SoC | 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 | 0.6 Events | Standard Deviation 0.83 |
p-value: 0.15295% CI: [0.86, 2.53]Negative binomial regression model
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).
Time frame: At any time post-discharge (from Visits 4 to 10), up to 180 days
Population: FAS. The FAS included all randomised participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: SZC | Number of Events (Hospital Admissions or ED Visits) With HK as a Contributing Factor, at Any Time Post-discharge up to 180 Days | 0.1 Events | Standard Deviation 0.24 |
| Arm B: SoC | Number of Events (Hospital Admissions or ED Visits) With HK as a Contributing Factor, at Any Time Post-discharge up to 180 Days | 0.1 Events | Standard Deviation 0.26 |
p-value: 0.23995% CI: [0.1, 1.81]Negative binomial regression model
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.
Time frame: At any time post-discharge (from Visits 4 to 10), up to 180 days
Population: FAS. The FAS included all randomised participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: SZC | 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 | NA Days |
| Arm B: SoC | 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 | NA Days |
p-value: 0.95195% CI: [0.58, 1.79]Regression, Cox
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.
Time frame: At any time post-discharge (from Visits 4 to 10), up to 180 days
Population: FAS. The FAS included all randomised participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: SZC | 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 | 136 Days |
| Arm B: SoC | 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 | NA Days |
p-value: 0.74395% CI: [0.56, 1.51]Regression, Cox
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.
Time frame: At any time post-discharge (from Visits 4 to 10), up to 180 days
Population: FAS. The FAS included all randomised participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: SZC | 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 | NA Days |
| Arm B: SoC | 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 | NA Days |
p-value: 0.25895% CI: [0.07, 1.83]Regression, Cox
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.
Time frame: At any time post-discharge (from Visits 4 to 10), up to 180 days
Population: FAS. The FAS included all randomised participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: SZC | Time to First Occurrence of RAASi Down-titration (or Discontinuation) at Any Time Post-discharge up to 180 Days | NA Days |
| Arm B: SoC | Time to First Occurrence of RAASi Down-titration (or Discontinuation) at Any Time Post-discharge up to 180 Days | NA Days |
p-value: 0.51595% CI: [0.5, 4.35]Regression, Cox