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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05347693
Other study ID # D9480C00023
Secondary ID 2021-003527-14
Status Recruiting
Phase Phase 4
First received
Last updated
Start date March 24, 2022
Est. completion date December 25, 2024

Study information

Verified date May 2024
Source AstraZeneca
Contact AstraZeneca Clinical Study Information Center
Phone 1-877-240-9479
Email information.center@astrazeneca.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 130
Est. completion date December 25, 2024
Est. primary completion date December 25, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years to 130 Years
Eligibility 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.

Study Design


Intervention

Drug:
Sodium Zirconium Cyclosilicate (SZC)
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 standard of care
Local SoC in the country to be used as per local label

Locations

Country Name City State
Belgium Research Site Belgium
Belgium Research Site Bonheiden
Belgium Research Site Dendermonde
Belgium Research Site Leuven
Belgium Research Site Lodelinsart
France Research Site Annonay
France Research Site Ars-Laquenexy
France Research Site La Tronche
France Research Site Nice
France Research Site Saint-priest En Jarez
Germany Research Site Kaiserslautern
Italy Research Site Acireale
Italy Research Site Bari
Italy Research Site Foggia
Italy Research Site Parma
Italy Research Site Pavia
Italy Research Site Pavia
Italy Research Site Roma
Netherlands Research Site Amsterdam
Netherlands Research Site Eindhoven
Netherlands Research Site Groningen
Netherlands Research Site Rotterdam
Spain Research Site Alcalá De Henares
Spain Research Site Algeciras
Spain Research Site Alicante
Spain Research Site Almería
Spain Research Site Badajoz
Spain Research Site Barcelona
Spain Research Site Burgos
Spain Research Site Getafe
Spain Research Site Madrid
Spain Research Site Madrid
Spain Research Site Madrid
Spain Research Site Palma de Mallorca
Spain Research Site Salamanca
Spain Research Site San Sebastián de los Reyes
Spain Research Site Santiago de Compostela
Spain Research Site Sevilla
Spain Research Site Talavera de la Reina
Spain Research Site Zamora
United Kingdom Research Site Cardiff
United Kingdom Research Site Doncaster
United Kingdom Research Site Edinburgh
United Kingdom Research Site Hull
United Kingdom Research Site Leicester
United Kingdom Research Site London
United Kingdom Research Site Salford
United Kingdom Research Site Stevenage
United Kingdom Research Site York

Sponsors (1)

Lead Sponsor Collaborator
AstraZeneca

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Other Adverse Events (AE) Assessments related to AEs cover: Occurrence/frequency, Relationship to SZC as assessed by investigator, Intensity, Seriousness, Death, AEs leading to discontinuation of SZC. From time of signature of the ICF, throughout the treatment period and including the follow-up period, 201 days maximum
Other Weight in kilograms Weight will be measured using the same scale and in the same state of dress as part of vital signs From time of signature of the ICF, throughout the treatment period and including the follow-up period, 201 days maximum
Other Height in centimeters Height will be measured as part of vital signs. Height will be measured at screening visit
Other Blood pressure (BP) in mmHg Blood pressure should be measured with a completely automated device in triplicate with at least 1-minute intervals between measurements after being comfortably at rest in a seated position with the back and feet supported quietly for at least 5 minutes. Manual techniques will be used only if an automated device is not available. The same device should preferably be used for the participant during the course of the study and in the same arm. From time of signature of the ICF, throughout the treatment period and including the follow-up period, 201 days maximum
Other Pulse rate in beats/min Pulse rate should be measured with a completely automated device in triplicate with at least 1-minute intervals between measurements after being comfortably at rest in a seated position with the back and feet supported quietly for at least 5 minutes. Manual techniques will be used only if an automated device is not available. The same device should preferably be used for the participant during the course of the study and in the same arm. From time of signature of the ICF, throughout the treatment period and including the follow-up period, 201 days maximum
Other Clinical safety laboratory tests Serum electrolytes values(mmol/L), serum BUN(mmol/L), urinalysis and others From time of signature of the ICF, throughout the treatment period and the follow-up period, 201 days maximum
Other Electrocardiograms (ECG) An ECG will be performed throughout study participation and according to clinical judgment in connection with severe hypokalaemia (K+ < 3.0 mmol/L), severe HK (K+ > 6.0 mmol/L), or any symptoms or clinical events suggesting cardiac arrhythmia. From time of signature of the ICF, throughout the treatment period and the follow-up period, 201 days maximum
Other Time to first occurrence of any component of hospital admission or ED visit, both with HK as a contributing factor, or all-cause death To evaluate the effect of continuing SZC as part of the discharge medications, compared to SoC, in reducing the incidence of the composite outcome of hospital admissions or ED visits with HK as a contributing factor or all-cause death Up to 180 days post-discharge
Other Time to first occurrence of either hospital admission with HK as a contributing factor or allcause death To evaluate the effect of continuing SZC as part of the discharge medications, compared to SoC, in reducing the incidence of hospital admissions with HK as a contributing factor or all-cause death Up to 180 days post-discharge
Other Time to first occurrence of either ED visit with HK as a contributing factor or all-cause death To evaluate the effect of continuing SZC as part of the discharge medications, compared to SoC, in reducing the incidence of ED visits with HK as a contributing factor or all-cause death Up to 180 days post-discharge
Other Time to first occurrence of any component of all-cause hospitalisations, ED visits, use of rescue therapy for HK or all-cause death in each arm To evaluate the effect of continuing SZC as part of the discharge medications, compared to SoC, in reducing the incidence of the composite outcome of all-cause hospitalisations, ED visits, all cause death, or use of rescue therapy for HK Up to 180 days post-discharge
Other K+ level To evaluate the effect of continuing SZC as part of the discharge medications, compared to SoC, on mean K+ levels Up to 180 days post-discharge
Other Number of hospital admissions with HK as a contributing factor To evaluate the effect of continuing SZC as part of the discharge medications, compared to SoC, in reducing the number of hospital admissions with HK as a contributing factor Up to 180 days post-discharge
Other Time to first occurrence of K-binder use in each arm To evaluate the effect of continuing SZC as part of discharge medications, compared to SoC in reducing the incidence of K-binder use Up to 180 days post-discharge
Other Frequency of the use of K-binder to treat HK in each arm To evaluate the effect of continuing SZC as part of discharge medications, compared to SoC in reducing the frequency and duration of K-binder use Up to 180 days post-discharge
Other Time to first occurrence of rescue therapy use in each arm To evaluate the effect of continuing SZC as part of the discharge medications, compared to SoC, in reducing the incidence of rescue therapy for HK use up to 180 days post-discharge
Other Time to first occurrence of all-cause hospitalisations, ED visits, or outpatient visits in each arm To evaluate the effect of continuing SZC as part of the discharge medications, compared to SoC, in reducing the incidence of the composite outcome of all-cause hospitalisations, ED visits, or outpatient visits up to 180 days post-discharge
Other Rate of change in (slope) eGFR (estimated glomerular filtration rate) from inpatient phase To evaluate the effect of continuing SZC as part of the discharge medications, compared to SoC, in the change in eGFR 90 and 180 days post-discharge
Other Time to first occurrence of dialysis initiation in each arm To evaluate the effect of continuing SZC as part of the discharge medications, compared to SoC, in the incidence of dialysis initiation up to 180 days post-discharge
Other Time to first occurrence of ICU (intensive care unit) admissions in each arm To evaluate the effect of continuing SZC as part of the discharge medications, compared to SoC, in reducing the incidence of ICU admissions up to 180 days post-discharge
Other Frequency (%) of participants on RAASi (renin-angiotensin-aldosterone system inhibitor) at discharge who remained on / increased / decreased / initiated RAASi This exploratory endpoint will descriptively summarise the use of RAASi in each treatment arm 90 and 180 days post-discharge
Primary Occurrence (yes/no) of normokalaemia (NK) (potassium [K+] between 3.5 and 5.0 mmol/L, inclusive) To evaluate the efficacy of continuing SZC as part of the discharge medications, compared to SoC, in maintaining NK Up to 180 days post-discharge
Secondary Time to first occurrence of all-cause hospital admissions or ED visits with HK as a contributing factor, all-cause death, or use of rescue therapy for HK To evaluate the effect of continuing SZC as part of the discharge medications, compared to SoC, in reducing the incidence of the composite outcome 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 Up to 180 days post-discharge
Secondary Time to first occurrence of all-cause hospital admission or ED visit, with HK as a contributing factor To evaluate the effect of continuing SZC as part of the discharge medications, compared to SoC, in reducing the incidence of hospital admissions or ED visit with HK as a contributing factor Up to 180 days post-discharge
Secondary Number of all-cause hospital admission or ED visits, with HK as a contributing factor To evaluate the effect of continuing SZC as part of the discharge medications, compared to SoC, in reducing the number of all-cause hospital admissions or ED visits with HK as a contributing factor Up to 180 days post-discharge
Secondary Time to first occurrence of hospital admission or ED visit with HK as a contributing factor between the SZC and SoC arms. To evaluate the effect of continuing SZC as part of the discharge medications, compared to SoC, in reducing the incidence of hospital admissions or ED visits with HK as a contributing factor. Up to 180 days post-discharge
Secondary Incidence rate of hospital admission or ED visit with HK as a contributing factor between the SZC and SoC arms. To evaluate the effect of continuing SZC as part of the discharge medications, compared to SoC, in reducing the number of hospital admissions or ED visits with HK as a contributing factor. Up to 180 days post-discharge
Secondary Time to first occurrence of RAASi down-titration (or discontinuation) To evaluate the effect of continuing SZC as part of the discharge medications compared to SoC on reducing the risk of RAASi down-titration (or discontinuation) Up to 180 days post-discharge
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