Study of SZC and Enhanced Nutrition Advice Compared to SoC in Dialysis Patients with Hyperkalaemia - GRAZE

Study identifier:D9480C00014

ClinicalTrials.gov identifier:NCT04997161

EudraCT identifier:2021-000457-81

CTIS identifier:N/A

Terminated/Withdrawn

Official Title

An Open-Label, Randomised, Controlled, Parallel-Design, Multicentre, Phase IV Study of Sodium Zirconium Cyclosilicate and Enhanced Nutrition Advice Compared to Standard of Care in Dialysis Patients with Hyperkalaemia (GRAZE)

Medical condition

Hyperkalaemia

Phase

Phase 4

Healthy volunteers

Study drug

Sodium Zirconium Cyclosilicate (SZC)

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 17 Aug 2021

Primary Completion Date: 17 Nov 2021

Study Completion Date: 17 Nov 2021

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Dec 2022 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

1. Participant must be ≥18 years of age at the time of signing the informed consent.
2. Participants with prevalent HK (S-K+ >5.5 mmol/L at the end of LIDI) not requiring acute treatment.
3. Receiving haemodialysis 3 times a week with stable vascular access for at least 3 months before screening visit.
4. Participants who have and are able and willing to use smart phone (android or iOS) nutrition app.
5. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Female participants of childbearing potential must have a negative pregnancy test.
• Female participants must be 1 year post-menopausal, surgically sterile, or using 1 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.
6. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in the protocol.

Exclusion Criteria

1. As judged by the investigator or sponsor, any medical condition (including active, clinically significant infection) that may pose a safety risk to the participant in this study, may confound safety or efficacy assessments and jeopardise the quality of data, or may interfere with study participation.
2. Myocardial infarction, acute coronary syndrome (ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, or unstable angina), stroke, seizure, thrombotic/thromboembolic event (eg, deep vein thrombosis or pulmonary embolism, but excluding vascular access thrombosis), percutaneous transluminal coronary angioplasty, or coronary artery bypass graft within 12 weeks prior to screening visit.
3. Severe leucocytosis (>20 × 109 /L) or thrombocytosis (≥450 × 109 /L) during screening.
4. Polycythaemia (haemoglobin >14 g/dL) during screening.
5. Severe constipation, bowel obstruction, post-operative motility disorders.
6. Scheduled date for living donor kidney transplant.
7. Participants with a life expectancy of less than 6 months.
8. Females of childbearing potential, unless using contraception as detailed in the protocol or sexually abstinent.
9. Currently pregnant (confirmed with positive pregnancy test) or breast-feeding.
10. Presence of cardiac arrhythmias or conduction defects that require immediate treatment at
HCP discretion.
11. History of alcohol or drug abuse within 2 years prior to screening visit.
12. History of QT prolongation associated with other medications that required discontinuation of that medication.
13. Congenital long QT syndrome or QT interval corrected for heart rate (QTc) using Fridericia’s method (QTcF) >550 ms.
14. Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted.
15. If the participant has evidence of Coronavirus disease 2019 (COVID-19) within 2 weeks
prior to screening (see Appendix D), the participant cannot be enrolled in the study.
16. Participants treated with SZC, sodium polystyrene sulfonate (SPS: Kayexalate™; Resonium™ A), calcium polystyrene sulfonate (CPS: Calcium Resonium™), or
patiromer (Veltassa™) 1 within 4 weeks before screening.
17. Participants with a known hypersensitivity or previous anaphylaxis to SZC or any of the excipients of the product.
18. Participants unable to take oral SZC.
Prior/Concurrent Clinical Study Experience
19. Participation in another clinical study with an investigational product administered during
the month before screening2 .
20. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study site).
21. 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.
22. Previous enrolment in the present study.

No locations available

Arms	Assigned Interventions
Experimental: SZC arm with enhanced dietary advice Participants will continue taking Sodium Zirconium Cyclosilicate (SZC), which can be titrated up or down to maintain S-K+ in the range 3.5-5.5 mmol/L; participants will also receive enhanced nutritional advice to consume fruit and vegetables. Advice will be provided by dietitians at study visits and by Noom app between visits.	Drug: Sodium Zirconium Cyclosilicate (SZC) Participants in the active arm will receive SZC dosed as per the local label to control hyperkalaemia and maintain normokalaemia. Other Name: SZC Other: Enhanced dietary advice Participants will receive enhanced dietary advice in addition to taking SZC. This will include advice from dietitians to consume fruit and vegetables. Participants will be encouraged to consume up to 70 mmol K+ per day. Other Name: Enhanced dietary advice
Other: SoC arm with standard dietary advice SZC will be withdrawn and participants will receive SoC as per site practice, including dietary K+ restriction. Dietary advice will be given by dietitians at study visits and by Noom app between study visits.	Other: Standard dietary advice including K+ restriction. Participants randomised to the SoC arm of the Diet Comparison Phase will receive standard dietary advice including K+ restriction. Other Name: Standard dietary advice

Arms

Assigned Interventions

Experimental: SZC arm with enhanced dietary advice
Participants will continue taking Sodium Zirconium Cyclosilicate (SZC), which can be titrated up or down to maintain S-K+ in the range 3.5-5.5 mmol/L; participants will also receive enhanced nutritional advice to consume fruit and vegetables. Advice will be provided by dietitians at study visits and by Noom app between visits.

Drug: Sodium Zirconium Cyclosilicate (SZC)
Participants in the active arm will receive SZC dosed as per the local label to control hyperkalaemia and maintain normokalaemia.

Other Name: SZC

Other: Enhanced dietary advice
Participants will receive enhanced dietary advice in addition to taking SZC. This will include advice from dietitians to consume fruit and vegetables. Participants will be encouraged to consume up to 70 mmol K+ per day.

Other Name: Enhanced dietary advice

Other: SoC arm with standard dietary advice
SZC will be withdrawn and participants will receive SoC as per site practice, including dietary K+ restriction. Dietary advice will be given by dietitians at study visits and by Noom app between study visits.

Other: Standard dietary advice including K+ restriction.
Participants randomised to the SoC arm of the Diet Comparison Phase will receive standard dietary advice including K+ restriction.

Other Name: Standard dietary advice

Documents available

Clinical Study Protocol-redacted
Download
Statistical Analysis Plan-redacted
Download
CSR synopsis-redacted
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Eric Wittbrodt

AstraZeneca, Biopharmaceuticals Medical

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Clinical Study Protocol-redacted

Statistical Analysis Plan-redacted

CSR synopsis-redacted

Trial Results Summaries