Resumen

The purpose of this study is to evaluate the effect of Sodium Zirconium Cyclosilicate (SZC) on arrhythmia-related cardiovascular outcomes in participants on chronic hemodialysis with recurrent hyperkalemia.

Descripción detallada

This is an international, multicenter, event-driven, randomized, double-blind, parallel group, placebo-controlled study, evaluating the utility of SZC versus placebo to reduce the incidence of sudden cardiac death (SCD), stroke, and arrhythmia-related hospitalizations, interventions, and emergency department (ED) visits in participants on chronic hemodialysis with recurrent hyperkalemia.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 130 YearsSexo: ALL

Criterios de inclusión

Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol
Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses
Must be ≥ 18 years of age, at the time of signing the ICF.
Receiving hemodialysis (or hemodiafiltration) 3 times a week for treatment of ESRD for ≥ 4 months before enrollment
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
At least 2 out of 3 pre-dialysis S K ≥ 5.5 mmol/L after the LIDI during screening
Negative pregnancy test for female participants of childbearing potential
Female participants must be 1 year postmenopausal, surgically sterile, or using one highly effective form of birth control (defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly). They should have been stable on their chosen method of birth control for a minimum of 3 months before entering the study and willing to remain on the birth control until 12 weeks after the last dose

Criterios de exclusión

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)
Presence of cardiac arrhythmias or conduction defects that require immediate treatment
Participants who have a pacemaker or implantable cardiac defibrillator
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
History of QT prolongation associated with other medications that required discontinuation of that medication
Congenital long QT syndrome
QTcF \> 550 msec
Atrial fibrillation requiring immediate/urgent intervention at screening or randomizations
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
Participation in another clinical study with an investigational product, device, or non-standard hemodialysis procedure administered within one month before screening
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 randomization in the present study
Females who are pregnant (confirmed with positive pregnancy test or a uterine ultrasound if pregnancy test result is questionable), breastfeeding, or planning to become pregnant during the study
Known hypersensitivity or previous anaphylaxis to SZC or to components thereof
Scheduled date for living donor kidney transplant
Sustained Ventricular Tachycardia \> 30 seconds requiring assessment / intervention

Intervenciones

drug

Sodium Zirconium Cyclosilicate (SZC)

Powder for oral suspension in a sachet. A dose is titrated in 5 g increments during a period of 4 weeks from 5 g up to 15 g qd on non-dialysis days. Afterward, the dose is adjusted monthly (or more frequent based on clinical judgment) depending on the current potassium value as measured after the long interdialytic interval (LIDI).

drug

SZC Placebo

Powder for oral suspension in a sachet. A dose is titrated in 5 g increments during a period of 4 weeks from 5 g up to 15 g qd on non-dialysis days. Afterward, the dose is adjusted monthly (or more frequent based on clinical judgment) depending on the current potassium value as measured after the LIDI.

Ubicaciones

Research Site

Córdoba, Argentina

Research Site

Junín, Argentina

Research Site

Mar del Plata, Argentina

Research Site

Pergamino, Argentina

Research Site

San Luis, Argentina

Research Site

San Luis, Argentina

Research Site

Santa Rosa, Argentina

Research Site

Sarandí, Argentina

Patrocinadores

PrincipalAstraZeneca

An International, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of Sodium Zirconium Cyclosilicate on Arrythmia-related Cardiovascular Outcomes in Participants on Chronic Hemodialysis With Recurrent Hyperkalemia (DIALIZE-Outcomes)

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Sodium Zirconium Cyclosilicate (SZC)

SZC Placebo

Ubicaciones

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Patrocinadores