Pre-dialysis hyperkalemia in patients with end stage renal disease (ESRD) on chronic hemodialysis MedDRA version: 21.1 Level: PT Classification code 10020646 Term: Hyperkalaemia System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in the protocol 2. Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses 3. Must be = 18 years of age, at the time of signing the ICF. 4. Receiving hemodialysis (or hemodiafiltration) 3 times a week for treatment of ESRD for = 4 months before enrollment 5. Must have hemodialysis access consisting of an arteriovenous fistula, arteriovenous graft, or tunneled (permanent) catheter which is expected to remain in place for the entire duration of the study 6. At least 2 out of 3 pre-dialysis S K = 5.5 mmol/L after the LIDI during screening 7. Female participants must be 1 year postmenopausal or surgically sterile. (Women will be considered postmenopausal if they have been amenorrhoeic for 12 months prior to the planned date of randomization without an alternative medical cause. Surgical sterilization includes: hysterectomy, bilateral oophorectomy, or bilateral salpingectomy.) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 1900 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 900
Exclusion criteria
Exclusion criteria: 1. Pseudohyperkalemia secondary to hemolyzed blood specimen (this situation is not considered screening failure, sampling or full screening can be postponed to a later time as applicable) 2. Presence of cardiac arrhythmias or conduction defects that require immediate treatment 3. Participants who have a pacemaker or implantable cardiac defibrillator 4. Any medical condition, including active, clinically significant infection or liver disease, that in the opinion of the investigator or sponsor may pose a safety risk to a participant in this study, confound safety or efficacy assessment and jeopardize the quality of the data, or interfere with study participation, or any other restrictions or contraindications in the local prescribing information for SZC 5. History of QT prolongation associated with other medications that required discontinuation of that medication 6. Congenital long QT syndrome 7. QTcF > 550 msec 8. Atrial Fibrillation requiring immediate/urgent intervention at screening or randomizations 9. Treated with sodium polystyrene sulfonate (SPS, Kayexalate, Resonium), calcium polystyrene sulfonate (CPS, Resonium Calcium), patiromer (Veltassa), or SZC (Lokelma) within 7 days before screening or anticipated requiring chronic use of any of these agents during the study. If participant requires rescue therapy (potassium binder or dialysate S-K change during screening period), the participant will be screen failed. 10. Participation in another clinical study with an investigational product, device, or non-standard hemodialysis procedure administered within one month before screening. 11. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) 12. 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 13. Previous randomization in the present study 14. Female participants of childbearing potential 15. Known hypersensitivity or previous anaphylaxis to SZC or to components thereof 16. Scheduled date for living donor kidney transplant 17. Sustained Ventricular Tachycardia > 30 seconds requiring assessment / intervention
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of SZC compared with placebo in reducing the incidence of the primary composite endpoint of sudden cardiac death (SCD), all stroke, or hospitalization/intervention/emergency department (ED) visit due to arrhythmias;Secondary Objective: - To evaluate the efficacy of SZC compared with placebo in maintaining normokalemia at one year - To evaluate the efficacy of SZC compared with placebo in reducing the incidence of hospitalization/intervention/ED visit due to arrhythmias - To evaluate the efficacy of SZC compared with placebo in reducing hospitalizations/interventions/ED visits due to arrhythmias - To evaluate the efficacy of SZC compared with placebo in reducing the need for rescue therapy for hyperkalemia - To evaluate the efficacy of SZC compared with placebo in preventing severe hyperkalemia at one year - To evaluate the efficacy of SZC compared with placebo in reducing the incidence of SCD - To evaluate the efficacy of SZC compared with placebo in reducing the incidence of all stroke - To evaluate the efficacy of SZC compared with placebo in reducing the incidence of cardiovascular (CV) death - To evaluate the efficacy of SZC compared with placebo in reducing the incidence of all-cause mortality;Primary end point(s): Time to first occurrence of SCD, stroke, or hospitalization/intervention/ED visit due to arrhythmias (AF, bradycardia, asystole, ventricular tachyarrhythmia [such as VF, VT, etc.]);Timepoint(s) of evaluation of this end point: It is expected that the primary endpoint events will be collected for an average of 37 months post-randomization. The individual follow-up times will vary, as the study is event-driven aiming for 730 events. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - S-K of 4.0-5.5 mmol/L (yes/no) after the LIDI at the 12 month visit - Time to first occurrence of hospitalization/intervention/ED visit due to arrhythmias (AF, bradycardia, asystole, ventricular tachyarrhythmia [such as VF, VT, etc.]) - Number of hospitalizations/interventions/ED visits due to arrhythmias (AF, bradycardia, asystole, or ventricular tachyarrhythmia [such as VF, VT, etc.]) - Time to first instance of rescue therapy use for hyperkalemia - S-K > 6.5 mmol/L (yes/no) after the LIDI at the 12 month visit - Time to SCD - Time to first occurrence of stroke - Time to CV death - Time to death of any cause;Timepoint(s) of evaluation of this end point: It is expected that the secondary endpoint events will be collected for an average of 37 months post-randomization. The individual follow-up times will vary, as the study is event-driven aiming for 730 events. S-K related endpoints will be evaluated at 12 months after randomization. | — |
Countries
Argentina, Austria, Brazil, Bulgaria, Canada, China, Czechia, Czech Republic, Germany, Hungary, India, Italy, Japan, Malaysia, Mexico, Peru, Poland, Russian Federation, Slovakia, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States, Viet Nam
Contacts
Public ContactClinical Study Information Center
AstraZeneca
Outcome results
None listed