Back to resultsStudy of SZC and Enhanced Nutrition Advice Compared to SoC in Dialysis Patients With Hyperkalaemia (GRAZE)
Primary Purpose
Hyperkalaemia
Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Sodium Zirconium Cyclosilicate (SZC)
Enhanced dietary advice
Standard dietary advice including K+ restriction.
Sponsored by
About this trial
This is an interventional treatment trial for Hyperkalaemia focused on measuring Hyperkalaemia, Dialysis Patients
Eligibility Criteria
Inclusion Criteria:
- Participant must be ≥18 years of age at the time of signing the informed consent.
- Participants with prevalent HK (S-K+ >5.5 mmol/L at the end of LIDI) not requiring acute treatment.
- Receiving haemodialysis 3 times a week with stable vascular access for at least 3 months before screening visit.
- Participants who have and are able and willing to use smart phone (android or iOS) nutrition app.
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.
- 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:
- 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.
- 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.
- Severe leucocytosis (>20 × 109 /L) or thrombocytosis (≥450 × 109 /L) during screening.
- Polycythaemia (haemoglobin >14 g/dL) during screening.
- Severe constipation, bowel obstruction, post-operative motility disorders.
- Scheduled date for living donor kidney transplant.
- Participants with a life expectancy of less than 6 months.
- Females of childbearing potential, unless using contraception as detailed in the protocol or sexually abstinent.
- Currently pregnant (confirmed with positive pregnancy test) or breast-feeding.
- Presence of cardiac arrhythmias or conduction defects that require immediate treatment at HCP discretion.
- History of alcohol or drug abuse within 2 years prior to screening visit.
- History of QT prolongation associated with other medications that required discontinuation of that medication.
- Congenital long QT syndrome or QT interval corrected for heart rate (QTc) using Fridericia's method (QTcF) >550 ms.
- Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted.
- 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.
- 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.
- Participants with a known hypersensitivity or previous anaphylaxis to SZC or any of the excipients of the product.
- Participants unable to take oral SZC. Prior/Concurrent Clinical Study Experience
- Participation in another clinical study with an investigational product administered during the month before screening2 .
- 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 enrolment in the present study.
Sites / Locations
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
SZC arm with enhanced dietary advice
SoC arm with standard dietary advice
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Change in Serum Potassium
Change in serum potassium taken at long interdialytic-dialysis interval visits Month 3, Month 4, and Month 5 compared to baseline
Secondary Outcome Measures
Change From Baseline in Fruit and Vegetable Consumption Determined by Participant-reported Intake Using Noom App From Month 2 to Month 5
Change from baseline in fruit and vegetable consumption determined by participant-reported intake using Noom app from Month 2 to Month 5
Effect of the Combination of Sodium Zirconium Cyclosilicate and Enhanced Nutritional Advice as Compared to Standard of Care on Participant-reported Chronic Kidney Disease Symptoms, Physical and Mental Health, and Satisfaction With Treatment
Electronic versions of the following:
Kidney Disease and Quality of Life-36 item (KDQOL-36; symptoms/problems, Physical Component Summary and Mental Component Summary, Burden of Kidney Disease and Effects of Kidney Disease)
EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)
Abbreviated Treatment Satisfaction Questionnaire for Medication (9 items) (TSQM-9)
Patients' Global Impression of Change (PGIC)
Effect of the Combination of Sodium Zirconium Cyclosilicate and Enhanced Nutritional Advice to Consume Fruit and Vegetables as Compared to Standard of Care in Maintaining Serum Potassium Levels
Effect of the combination of sodium zirconium cyclosilicate and enhanced nutritional advice to consume fruit and vegetables as compared to standard of care in maintaining serum potassium levels within a range of 3.5 to 5.5 mmol/L, without requiring rescue therapy for hyperkalaemia.
Binary response (responder/non-responder) with criteria that at least 66% of serum potassium values taken at long interdialytic-dialysis interval visits in Months 3, 4, and 5 fall between 3.5 and 5.5 mmol/L.
Receiving rescue therapy or a potassium binder for hyperkalaemia during the final 3 months of the study was to result in a non-response.
Safety and Tolerability of Sodium Zirconium Cyclosilicate and Enhanced Nutritional Advice as Compared to Standard of Care
Safety and tolerability were to be evaluated in terms of adverse events (AEs), vital signs, clinical laboratory, interdialytic weight gain, and electrocardiograms.
Assessments related to AEs covered occurrence/frequency, relationship to sodium zirconium cyclosilicate as assessed by Investigator, intensity, seriousness, death, and AEs leading to discontinuation of sodium zirconium cyclosilicate.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04997161
Brief Title
Study of SZC and Enhanced Nutrition Advice Compared to SoC in Dialysis Patients With Hyperkalaemia
Acronym
GRAZE
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)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Terminated
Why Stopped
There is disconnect between dietary guidelines to limit potassium intake in dialysis and clinical practice. The number of unknowns and differences make the results unlikely to be translatable into clinical practice and will not benefit patients.
Study Start Date
August 17, 2021 (Actual)
Primary Completion Date
November 17, 2021 (Actual)
Study Completion Date
November 17, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Prescribing Sodium zirconium cyclosilicate (SZC) with enhanced nutritional advice to participants with hyperkalaemia on haemodialysis will reduce serum K+ (S-K+ ) and enable the consumption of more fruit and vegetables and more satisfying diet. The study aims to show that participants using SZC achieve S-K+ reduction as well as participants on SoC (other than K+ binders), without the need for restricting K+ in the diet.
Detailed Description
This is a Phase IV, randomised, controlled, open-label, parallel-group, multicentre, prospective study to evaluate the effect of the combination of SZC and enhanced nutritional advice to consume fruit and vegetables as compared to SoC in reducing S-K+ levels in participants with hyperkalaemia on haemodialysis. Following 7-day screening, all participants who are enrolled will begin an up to 1-month HK Treatment Phase with SZC as per local label. Participants will receive dietary advice consistent with SoC at that site, including K+ restriction. A 4-month Diet Comparison Phase will begin next with participants being randomised to either continue taking SZC, which can be titrated as needed to maintain target S-K+ , and receive enhanced nutritional advice to consume fruit and vegetables (SZC arm), or SZC will be withdrawn and participants will receive SoC, including dietary K+ restriction (SoC arm).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperkalaemia
Keywords
Hyperkalaemia, Dialysis Patients
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Parallel: Participants are assigned to two groups in parallel for the duration of the study.
Following 7-day screening, all participants who are enrolled will begin an up to 1-month HK Treatment Phase with SZC as per local label. Participants will receive dietary advice consistent with SoC at that site, including K+ restriction. A 4-month Diet Comparison Phase will begin next with participants being randomised to either continue taking SZC, which can be titrated as needed to maintain target S-K+ , and receive enhanced nutritional advice to consume fruit and vegetables (SZC arm), or SZC will be withdrawn and participants will receive SoC, including dietary K+ restriction (SoC arm).
Masking
None (Open Label)
Allocation
Randomized
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SZC arm with enhanced dietary advice
Arm Type
Experimental
Arm Description
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.
Arm Title
SoC arm with standard dietary advice
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Sodium Zirconium Cyclosilicate (SZC)
Other Intervention Name(s)
SZC
Intervention Description
Participants in the active arm will receive SZC dosed as per the local label to control hyperkalaemia and maintain normokalaemia.
Intervention Type
Other
Intervention Name(s)
Enhanced dietary advice
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Standard dietary advice including K+ restriction.
Other Intervention Name(s)
Standard dietary advice
Intervention Description
Participants randomised to the SoC arm of the Diet Comparison Phase will receive standard dietary advice including K+ restriction.
Primary Outcome Measure Information:
Title
Change in Serum Potassium
Description
Change in serum potassium taken at long interdialytic-dialysis interval visits Month 3, Month 4, and Month 5 compared to baseline
Time Frame
Baseline to Month 5
Secondary Outcome Measure Information:
Title
Change From Baseline in Fruit and Vegetable Consumption Determined by Participant-reported Intake Using Noom App From Month 2 to Month 5
Description
Change from baseline in fruit and vegetable consumption determined by participant-reported intake using Noom app from Month 2 to Month 5
Time Frame
Month 2 to Month 5
Title
Effect of the Combination of Sodium Zirconium Cyclosilicate and Enhanced Nutritional Advice as Compared to Standard of Care on Participant-reported Chronic Kidney Disease Symptoms, Physical and Mental Health, and Satisfaction With Treatment
Description
Electronic versions of the following:
Kidney Disease and Quality of Life-36 item (KDQOL-36; symptoms/problems, Physical Component Summary and Mental Component Summary, Burden of Kidney Disease and Effects of Kidney Disease)
EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)
Abbreviated Treatment Satisfaction Questionnaire for Medication (9 items) (TSQM-9)
Patients' Global Impression of Change (PGIC)
Time Frame
From study start to study end
Title
Effect of the Combination of Sodium Zirconium Cyclosilicate and Enhanced Nutritional Advice to Consume Fruit and Vegetables as Compared to Standard of Care in Maintaining Serum Potassium Levels
Description
Effect of the combination of sodium zirconium cyclosilicate and enhanced nutritional advice to consume fruit and vegetables as compared to standard of care in maintaining serum potassium levels within a range of 3.5 to 5.5 mmol/L, without requiring rescue therapy for hyperkalaemia.
Binary response (responder/non-responder) with criteria that at least 66% of serum potassium values taken at long interdialytic-dialysis interval visits in Months 3, 4, and 5 fall between 3.5 and 5.5 mmol/L.
Receiving rescue therapy or a potassium binder for hyperkalaemia during the final 3 months of the study was to result in a non-response.
Time Frame
From study start to study end
Title
Safety and Tolerability of Sodium Zirconium Cyclosilicate and Enhanced Nutritional Advice as Compared to Standard of Care
Description
Safety and tolerability were to be evaluated in terms of adverse events (AEs), vital signs, clinical laboratory, interdialytic weight gain, and electrocardiograms.
Assessments related to AEs covered occurrence/frequency, relationship to sodium zirconium cyclosilicate as assessed by Investigator, intensity, seriousness, death, and AEs leading to discontinuation of sodium zirconium cyclosilicate.
Time Frame
From study start to study end
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
130 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participant must be ≥18 years of age at the time of signing the informed consent.
Participants with prevalent HK (S-K+ >5.5 mmol/L at the end of LIDI) not requiring acute treatment.
Receiving haemodialysis 3 times a week with stable vascular access for at least 3 months before screening visit.
Participants who have and are able and willing to use smart phone (android or iOS) nutrition app.
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.
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:
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.
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.
Severe leucocytosis (>20 × 109 /L) or thrombocytosis (≥450 × 109 /L) during screening.
Polycythaemia (haemoglobin >14 g/dL) during screening.
Severe constipation, bowel obstruction, post-operative motility disorders.
Scheduled date for living donor kidney transplant.
Participants with a life expectancy of less than 6 months.
Females of childbearing potential, unless using contraception as detailed in the protocol or sexually abstinent.
Currently pregnant (confirmed with positive pregnancy test) or breast-feeding.
Presence of cardiac arrhythmias or conduction defects that require immediate treatment at HCP discretion.
History of alcohol or drug abuse within 2 years prior to screening visit.
History of QT prolongation associated with other medications that required discontinuation of that medication.
Congenital long QT syndrome or QT interval corrected for heart rate (QTc) using Fridericia's method (QTcF) >550 ms.
Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted.
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.
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.
Participants with a known hypersensitivity or previous anaphylaxis to SZC or any of the excipients of the product.
Participants unable to take oral SZC. Prior/Concurrent Clinical Study Experience
Participation in another clinical study with an investigational product administered during the month before screening2 .
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 enrolment in the present study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric Wittbrodt, PharmD, MPH
Organizational Affiliation
AstraZeneca, Biopharmaceuticals Medical
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33411
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment:
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
IPD Sharing Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at:
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
IPD Sharing Access Criteria
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at:
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home
Links:
URL
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Description
Clinical Study Protocol-redacted
URL
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Description
Statistical Analysis Plan-redacted
URL
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Description
CSR synopsis-redacted
Learn more about this trial
Study of SZC and Enhanced Nutrition Advice Compared to SoC in Dialysis Patients With Hyperkalaemia
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