Study of SZC and Enhanced Nutrition Advice Compared to SoC in Dialysis Patients With Hyperkalaemia
Condition: Hyperkalaemia
MeSH terms: Hyperkalemia
Intervention: Sodium Zirconium Cyclosilicate (SZC); Enhanced dietary advice; Standard dietary advice including K+ restriction.
Intervention description: Participants in the active arm will receive SZC dosed as per the local label to control hyperkalaemia and maintain normokalaemia.; 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.; Participants randomised to the SoC arm of the Diet Comparison Phase will receive standard dietary advice including K+ restriction.
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention 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target S-K+ , and receive enhanced nutritional advice to consume fruit and vegetables (SZC arm), or SZC will be withdrawn and participants will receive SoC, including dietary K+ restriction (SoC arm).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)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: Hyperkalaemia; Dialysis Patients

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.
    

Eligibility 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.