E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Chronic Kidney Disease treated for Hyperkalaemia whilst in hospital, who are normokalemic and established on maintenance dose of SZC at discharge. |
|
E.1.1.1 | Medical condition in easily understood language |
Hyperkalemia means that the potassium level in the blood is higher than normal |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020646 |
E.1.2 | Term | Hyperkalaemia |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of continuing SZC as part of the discharge medications, compared to SoC, in maintaining NK |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the effect of continuing SZC as part of the discharge medications, compared to SoC: 1. in reducing the incidence of the composite outcome of hospital admissions or ED visits with HK as a contributing factor, all-cause death, or use of rescue-therapy for HK 2. in reducing the incidence of the composite outcome of hospital admissions with HK as a contributing factor, all-cause death, or use of rescue therapy for HK 3. in reducing the incidence of ED visits with HK as a contributing factor, all-cause death, or use of rescue therapy for HK 4. in reducing the incidence of the composite outcome of hospital admissions or ED visits with HK as a contributing factor or all-cause death 5. in reducing the incidence of hospital admissions with HK as a contributing factor or all-cause death 6. in reducing the incidence of ED visits with HK as a contributing factor or all-cause death |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1 Must be 18 years of age or older, at the time of signing the informed consent 2 Admitted to hospital (inpatient care; directly or from ED) 3 With: - diagnosed stage 3b to 5 CKD And/or - eGFR < 45 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. 4 Most recent recorded K+ measurement, either for this admission or at ED visit leading to this admission, should be between 5.5 and 6.5 mmol/L, inclusive 5 Male or female 6 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 the protocol. |
|
E.4 | Principal exclusion criteria |
1 Myocardial infarction, stroke, seizure, or a thrombotic/thromboembolic event (eg, deep vein thrombosis or pulmonary embolism, but excluding vascular access thrombosis) within 12 weeks prior to screening 2 Unable to take oral SZC drug mix 3 Recipient of or scheduled date for living donor kidney transplant 4 With a life expectancy of less than 6 months 5 Any medical condition (including active, clinically significant infection) that, in the opinion of the investigator or sponsor, may pose a safety risk to the participant in this study, which may confound safety or efficacy assessments and jeopardise the quality of data, or may interfere with study participation 6 Presence of cardiac arrhythmias or conduction defects that require immediate treatment 7 QT interval corrected by the Fridericia method (QTcF) > 550 msec 8 History of QT prolongation associated with other medications that required discontinuation of that medication 9 Congenital long QT syndrome 10 Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participant with atrial fibrillation controlled by medication is permitted. 11 Evidence of Coronavirus disease 2019 (COVID-19) within 2 weeks prior to screening (see Appendix C) 12 History of alcohol or drug abuse within 2 years prior to screening 13 Ongoing treatment with any K-binder at index hospital admission (initiation of SZC during ED visit immediately preceding the index hospital admission is allowed) 14 Renal replacement therapy, including chronic haemodialysis and peritoneal dialysis 15 Participation in another clinical study with an investigational product (IP) administered during the month before screening. Note: Participant vaccinated with COVID-19 vaccine whilst still under Emergency Use Utilisation will not be excluded from the study. 16 Known hypersensitivity to SZC or any of the excipients of the product 17 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) 18 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 19 Previous randomisation in the present study 20 For women only: Women of child-bearing potential (WOCBP; ie, those who are not chemically or surgically sterilised or who are not postmenopausal) who are not willing to use one of the methods of contraception described hereafter, from the time of signing the informed consent throughout the study and 4 weeks thereafter: (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 (IUD) (d) Intrauterine hormone-releasing system (IUS) (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. 21 For WOCBP only: Women who have a positive pregnancy test at screening OR women who are breastfeeding. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Occurrence (yes/no) of NK (K+ between 3.5 and 5.0 mmol/L, inclusive) at 180 days post-discharge. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 180 days post-discharge |
|
E.5.2 | Secondary end point(s) |
Time to first occurrence of: 1. hospital admissions or ED visits with HK as a contributing factor, use of rescue therapy for HK, or all-cause death (composite outcome) 2. hospital admission with HK as a contributing factor, all-cause death, or use of rescue therapy for HK 3. ED visits with HK as a contributing factor, all-cause death, or use of rescue therapy for HK 4, 5 and 6: either component of the composite outcome in point 1 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At any time post-discharge up to 180 days. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
France |
Germany |
Italy |
Netherlands |
Spain |
United Kingdom |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 6 |