Effect of Sodium Zirconium Cyclosilicate on Arrythmia-related Cardiovascular Outcomes in Participants on Chronic Hemodialysis With Recurrent Hyperkalemia (DIALIZE-Outcomes)

Hyperkalemia Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04847232
• Other study ID #: D9487C00001
• Secondary ID: 2020-005561-14
• Status: Terminated
• Phase: Phase 3
• Start date: April 30, 2021
• Est. completion date: March 7, 2024

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2698
• Est. completion date: March 7, 2024
• Est. primary completion date: March 7, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this 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. Negative pregnancy test for female participants of childbearing potential

8. 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

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. 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

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

Related Conditions & MeSH terms

• Hyperkalemia

Intervention

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).
• 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.

Locations

Country	Name	City	State
Argentina	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	Sarandi
Austria	Research Site	Graz
Austria	Research Site	Innsbruck
Brazil	Research Site	Brasilia
Brazil	Research Site	Curitiba
Brazil	Research Site	Curitiba
Brazil	Research Site	Joinville
Brazil	Research Site	Maringá
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Recife
Brazil	Research Site	Ribeirao Preto
Brazil	Research Site	Rio De Janeiro
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	São Paulo
Bulgaria	Research Site	Blagoevgrad
Bulgaria	Research Site	Gotse Delchev
Bulgaria	Research Site	Haskovo
Bulgaria	Research Site	Pleven
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Razlog
Bulgaria	Research Site	Samokov
Bulgaria	Research Site	Sandanski
Bulgaria	Research Site	Silistra
Bulgaria	Research Site	Smolyan
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Stara Zagora
Bulgaria	Research Site	Varna
Bulgaria	Research Site	Yambol
Canada	Research Site	Greenfield Park	Quebec
Canada	Research Site	Halifax	Nova Scotia
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Oshawa	Ontario
Canada	Research Site	Quebec
Canada	Research Site	Saint John	New Brunswick
Canada	Research Site	Sydney	Nova Scotia
Canada	Research Site	Toronto	Ontario
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Changzhou
China	Research Site	Chengdu
China	Research Site	Chengdu
China	Research Site	Dongguan
China	Research Site	Foshan
China	Research Site	Fuzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guilin
China	Research Site	Guiyang
China	Research Site	Guiyang
China	Research Site	Haikou
China	Research Site	Hangzhou
China	Research Site	Hefei
China	Research Site	Hohhot
China	Research Site	Huai'an
China	Research Site	Jinan
China	Research Site	Jinhua
China	Research Site	Jiujiang
China	Research Site	Kunming
China	Research Site	Lanzhou
China	Research Site	Lanzhou
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Nanjing
China	Research Site	Nanyang
China	Research Site	Ningbo
China	Research Site	Panjin
China	Research Site	Pingxiang
China	Research Site	Qingdao
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shengyang
China	Research Site	Shenzhen
China	Research Site	Siping
China	Research Site	Taian
China	Research Site	Taiyuan
China	Research Site	Tianjin
China	Research Site	Tianjin
China	Research Site	Urumqi
China	Research Site	Wenzhou
China	Research Site	Wuhan
China	Research Site	WuHan
China	Research Site	Wuhu
China	Research Site	Wuxi
China	Research Site	Xiamen
China	Research Site	Xianyang
China	Research Site	Yibin
China	Research Site	Yinchuan
China	Research Site	Zhengzhou
China	Research Site	Zhuzhou
Czechia	Research Site	Ceske Budejovice
Czechia	Research Site	Havlickuv Brod
Czechia	Research Site	Jilemnice
Czechia	Research Site	Klatovy
Czechia	Research Site	Liberec
Czechia	Research Site	Nove Mesto na Morave
Czechia	Research Site	Plzen
Czechia	Research Site	Praha 4
Czechia	Research Site	Tabor
Czechia	Research Site	Trebic
Germany	Research Site	Cloppenburg
Germany	Research Site	Düsseldorf
Germany	Research Site	Hannover
Germany	Research Site	Minden
Germany	Research Site	Potsdam
Germany	Research Site	Stuttgart
Germany	Research Site	Villingen-Schwenningen
Hungary	Research Site	Baja
Hungary	Research Site	Budapest
Hungary	Research Site	Kaposvár
Hungary	Research Site	Karcag
Hungary	Research Site	Kistarcsa
Hungary	Research Site	Miskolc
Hungary	Research Site	Nagykanizsa
Hungary	Research Site	Szombathely
India	Research Site	Ahmedabad
India	Research Site	Chennai
India	Research Site	Dhanvantari Nagar
India	Research Site	Nadiad
India	Research Site	Pune
Italy	Research Site	Bassano del Grappa
Italy	Research Site	Bergamo
Italy	Research Site	Bologna
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Italy	Research Site	Monza
Italy	Research Site	Parma
Italy	Research Site	Pavia
Italy	Research Site	Pesaro
Italy	Research Site	Roma
Italy	Research Site	San Giovanni Rotondo
Italy	Research Site	Verona
Japan	Research Site	Fujisawa-shi
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Hamamatsu-shi
Japan	Research Site	Kawasaki-shi
Japan	Research Site	Kumagaya-shi
Japan	Research Site	Kumamoto-shi
Japan	Research Site	Kyoto-shi
Japan	Research Site	Moriya-shi
Japan	Research Site	Nagano-shi
Japan	Research Site	Nagasaki-shi
Japan	Research Site	Nakagami-gun
Japan	Research Site	Okinawa-shi
Japan	Research Site	Omihachiman-shi
Japan	Research Site	Sashima-gun
Japan	Research Site	Setagaya-ku
Japan	Research Site	Shiroishi-shi
Japan	Research Site	Tamana-shi
Japan	Research Site	Toride-shi
Japan	Research Site	Tsuchiura-shi
Japan	Research Site	Tsuchiura-shi
Japan	Research Site	Tsukuba-shi
Japan	Research Site	Ushiku-shi
Japan	Research Site	Yatomi-shi
Malaysia	Research Site	Batu Caves
Malaysia	Research Site	Ipoh
Malaysia	Research Site	Melaka
Malaysia	Research Site	Seri Manjung
Mexico	Research Site	Chihuahua
Mexico	Research Site	Culiacán
Mexico	Research Site	D.F
Mexico	Research Site	Mazatlán
Mexico	Research Site	Mexico City
Mexico	Research Site	Monterrey
Mexico	Research Site	Morelia
Mexico	Research Site	San Luis Potosí
Mexico	Research Site	Veracruz
Mexico	Research Site	Xalapa
Mexico	Research Site	Zapopan
Peru	Research Site	Cusco
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Piura
Poland	Research Site	Gdansk
Poland	Research Site	Lezajsk
Poland	Research Site	Lódz
Poland	Research Site	Lódz
Poland	Research Site	Lublin
Poland	Research Site	Olesnica
Poland	Research Site	Olkusz
Poland	Research Site	Pszczyna
Poland	Research Site	Slupsk
Poland	Research Site	Tczew
Poland	Research Site	Wolomin
Poland	Research Site	Wroclaw
Poland	Research Site	Zory
Poland	Research Site	Zyrardów
Russian Federation	Research Site	Kemerovo
Russian Federation	Research Site	Mytischi
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Omsk
Russian Federation	Research Site	Penza
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Yaroslavl
Slovakia	Research Site	Žilina
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Komárno
Slovakia	Research Site	Kosice
Slovakia	Research Site	Lucenec
Slovakia	Research Site	Puchov
Spain	Research Site	Alcala de Henares
Spain	Research Site	Barcelona
Spain	Research Site	Cordoba
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Pamplona
Spain	Research Site	Valencia
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Keelung
Taiwan	Research Site	Linkou
Taiwan	Research Site	New Taipei
Taiwan	Research Site	New Taipei
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taipei City
Thailand	Research Site	Bangkok
Thailand	Research Site	Chiang Mai
Thailand	Research Site	Hat Yai
Thailand	Research Site	Ratchathewi
Turkey	Research Site	Adapazari
Turkey	Research Site	Ankara
Turkey	Research Site	Gaziantep
Turkey	Research Site	Kahramanmaras
Turkey	Research Site	Kayseri
Turkey	Research Site	Kocaeli
Ukraine	Research Site	Chernivts?
Ukraine	Research Site	Dnipro
Ukraine	Research Site	Ivano-Frankivsk
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Odesa
Ukraine	Research Site	Ternopil
Ukraine	Research Site	Uzhhorod
Ukraine	Research Site	Vinnytsia
Ukraine	Research Site	Zaporizhzhia
Ukraine	Research Site	Zaporizhzhia
United Kingdom	Research Site	Bristol
United Kingdom	Research Site	Leicester
United Kingdom	Research Site	Liverpool
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Preston
United Kingdom	Research Site	Salford
United Kingdom	Research Site	Swansea
United Kingdom	Research Site	Wolverhampton
United States	Research Site	Austin	Texas
United States	Research Site	Austin	Texas
United States	Research Site	Bakersfield	California
United States	Research Site	Baton Rouge	Louisiana
United States	Research Site	Bethlehem	Pennsylvania
United States	Research Site	Bloomfield	Connecticut
United States	Research Site	Bronx	New York
United States	Research Site	Brookhaven	Mississippi
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Columbus	Mississippi
United States	Research Site	Columbus	Georgia
United States	Research Site	Conroe	Texas
United States	Research Site	Denver	Colorado
United States	Research Site	Detroit	Michigan
United States	Research Site	El Paso	Texas
United States	Research Site	El Paso	Texas
United States	Research Site	Fort Lauderdale	Florida
United States	Research Site	Glendale	California
United States	Research Site	Granada Hills	California
United States	Research Site	Greenville	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Huntsville	Alabama
United States	Research Site	Iowa City	Iowa
United States	Research Site	Jersey City	New Jersey
United States	Research Site	Kalamazoo	Michigan
United States	Research Site	Kansas City	Missouri
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lawrenceville	Georgia
United States	Research Site	Lynwood	California
United States	Research Site	Manhasset	New York
United States	Research Site	Mesa	Arizona
United States	Research Site	Middlebury	Connecticut
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Nampa	Idaho
United States	Research Site	New Bern	North Carolina
United States	Research Site	Newark	Delaware
United States	Research Site	Norfolk	Virginia
United States	Research Site	Providence	Rhode Island
United States	Research Site	Roseville	Michigan
United States	Research Site	Saint George	Utah
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Diego	California
United States	Research Site	Spartanburg	South Carolina
United States	Research Site	Statesboro	Georgia
United States	Research Site	Tampa	Florida
United States	Research Site	Tupelo	Mississippi
United States	Research Site	Vacaville	California
United States	Research Site	Victorville	California
United States	Research Site	Virginia Beach	Virginia
United States	Research Site	Winston-Salem	North Carolina
Vietnam	Research Site	Bien Hoa
Vietnam	Research Site	Da Nang
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh City
Vietnam	Research Site	Hue

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Austria,  Brazil,  Bulgaria,  Canada,  China,  Czechia,  Germany,  Hungary,  India,  Italy,  Japan,  Malaysia,  Mexico,  Peru,  Poland,  Russian Federation,  Slovakia,  Spain,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse Events (AEs)/ Serious Adverse Events (SAEs)		From randomization/ screening visit through study completion during study visits every 3 months, over an average of 3 years
Other	Events of pre-dialysis hypokalemia (S-K < 3.0 mmol/L)		From randomization visit through study completion during study visits every 3 months, over an average of 3 years
Other	Change in interdialytic weight gain (kg) as compared to baseline		From randomization visit through study completion during study visits every 3 months, over an average of 3 years
Primary	Time to first occurrence of SCD, stroke, or hospitalization/intervention/ED visit due to arrhythmias (atrial fibrillation [AF], bradycardia, asystole, ventricular tachyarrhythmia [VF, VT, etc.])		From randomization visit through study completion during study visits every 3 months, over an average of 3 years
Secondary	S-K of 4.0-5.5 mmol/L (yes/no) after the long interdialytic interval (LIDI) at the 12 month visit		Evaluated at 12 months after randomization
Secondary	Time to first occurrence of hospitalization/intervention/ED visit due to arrhythmias (AF, bradycardia, asystole, Ventricular tachyarrhythmia [VF, VT etc.])		From randomization visit through study completion during study visits every 3 months, over an average of 3 years
Secondary	Number of hospitalizations/interventions/ED visits due to arrhythmias (AF, bradycardia, asystole, Ventricular tachyarrhythmia [VF, VT etc.])		From randomization visit through study completion during study visits every 3 months, over an average of 3 years
Secondary	Time to first instance of rescue therapy use for hyperkalemia		From randomization visit through study completion during study visits every 3 months, over an average of 3 years
Secondary	S-K > 6.5 mmol/L (yes/no) after the LIDI at the 12 month visit		Evaluated at 12 months after randomization
Secondary	Time to SCD		From randomization visit through study completion during study visits every 3 months, over an average of 3 years
Secondary	Time to first occurrence of stroke		From randomization visit through study completion during study visits every 3 months, over an average of 3 years
Secondary	Time to cardiovascular (CV) death		From randomization visit through study completion during study visits every 3 months, over an average of 3 years
Secondary	Time to death of any cause		From randomization visit through study completion during study visits every 3 months, over an average of 3 years