Study of SZC and Enhanced Nutrition Advice Compared to SoC in Dialysis Patients With Hyperkalaemia

NCT04997161 | Terminated Phase 4 Results FDA Drug

• 2 other identifiers: D9480C000142021-000457-81
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Hyperkalaemia

Keywords

Hyperkalaemia; Dialysis Patients

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline to Month 5

Secondary Outcomes (4)

• Change From Baseline in Fruit and Vegetable Consumption Determined by Participant-reported Intake Using Noom App From Month 2 to Month 5

  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

  From study start to study end

• 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

  From study start to study end

• Safety and Tolerability of Sodium Zirconium Cyclosilicate and Enhanced Nutritional Advice as Compared to Standard of Care

  From study start to study end

Study Arms (2)

SZC arm with enhanced dietary advice

EXPERIMENTAL

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); Other: Enhanced dietary advice

SoC arm with standard dietary advice

OTHER

SZC will be withdrawn and participants will receive SoC as per site practice, including dietary K+ restriction.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.

Interventions

Sodium Zirconium Cyclosilicate (SZC) DRUG

Participants in the active arm will receive SZC dosed as per the local label to control hyperkalaemia and maintain normokalaemia.

Also known as: SZC

SZC arm with enhanced dietary advice

Enhanced dietary advice OTHER

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.

SZC arm with enhanced dietary advice

Standard dietary advice including K+ restriction. OTHER

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

Also known as: Standard dietary advice

SoC arm with standard dietary advice

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

West Palm Beach, Florida, 33411, United States

Location

Related Links

• Clinical Study Protocol-redacted
• Statistical Analysis Plan-redacted
• CSR synopsis-redacted

MeSH Terms

Conditions

Hyperkalemia

Interventions

sodium zirconium cyclosilicate

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

The study was terminated by the sponsor with only 1 participant randomized. There was disconnect between dietary guidelines to limit potassium intake in dialysis and clinical practice.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Eric Wittbrodt, PharmD, MPH

  AstraZeneca, Biopharmaceuticals Medical

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: June 16, 2021
• First Posted: August 9, 2021
• Study Start: August 17, 2021
• Primary Completion: November 17, 2021
• Study Completion: November 17, 2021
• Last Updated: January 19, 2023
• Results First Posted: January 19, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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
• 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

Locations

US (1)