- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04217590
Reduce Incidence of Pre-Dialysis Hyperkalaemia With Sodium Zirconium Cyclosilicate in Chinese Subjects (DIALIZE China)
A Phase 3b, Multicentre, Prospective, Randomized, Double-Blind, Placebo-Controlled Study to Reduce Incidence of Pre-Dialysis Hyperkalaemia With Sodium Zirconium Cyclosilicate in Chinese Subjects
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Baotou, China, 14010
- Research Site
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Baotou, China, 014040
- Research Site
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Beijing, China, 100029
- Research Site
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Beijing, China, 100044
- Research Site
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Beijing, China, 100191
- Research Site
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Beijing, China, 102206
- Research Site
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Changchun, China, 130021
- Research Site
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Changchun, China, 130041
- Research Site
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Dongguan, China, 523009
- Research Site
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Hangzhou, China, 310014
- Research Site
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Hefei, China, 230001
- Research Site
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Hohhot, China, 010017
- Research Site
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Jinan, China, 250014
- Research Site
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Lanzhou, China, 730030
- Research Site
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Lanzhou, China, 730000
- Research Site
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Nanchang, China, 330006
- Research Site
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Nanjing, China, 210011
- Research Site
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Ningbo, China, 315000
- Research Site
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Ningbo, China, 315010
- Research Site
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Shanghai, China, 200080
- Research Site
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Shanghai, China, 201199
- Research Site
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Shanghai, China, 200065
- Research Site
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Shanghai, China, 200090
- Research Site
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Shanghai, China, 200233
- Research Site
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Shanghai, China, 200120
- Research Site
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Shanghai, China, 200240
- Research Site
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Shanghai, China, 200127
- Research Site
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Shanghai, China, 200232
- Research Site
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Shenzhen, China, 518035
- Research Site
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Shenzhen, China, 518053
- Research Site
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Tianjin, China, 300052
- Research Site
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Urumqi, China, CN-830004
- Research Site
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Wenzhou, China, 325027
- Research Site
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Wenzhou, China, 325000
- Research Site
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Yangzhou, China, 225001
- Research Site
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Yinchuan, China, 750004
- Research Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.
- Subject must be ≥ 18 years of age inclusive, at the time of signing the informed consent form.
- Subjects must have haemodialysis access consisting of an arteriovenous fistula, AV graft, or tunnelled (permanent) catheter which is expected to remain in place for the entire duration of the study.
- Receiving haemodialysis (or hemodiafiltration) 3 times a week for treatment of end-stage renal disease (ESRD) for at least 3 months before randomization.
- Pre-dialysis S-K > 5.4 mmol/L after long inter-dialytic interval and > 5.0 mmol/L after at least one short inter-dialytic interval during screening (as assessed by central lab).
- Prescribed dialysate K concentration ≤ 3 mmol/L during screening.
- Sustained Qb ≥ 200 ml/min and spKt/V ≥ 1.2 (or URR ≥ 63) on stable haemodialysis / haemodiafltration prescription during screening with prescription (time, dialyzer, blood flow [Qb], dialysate flow rate [Qd] and bicarbonate concentration) expected to remain unchanged during study.
- Subjects must be receiving dietary counselling appropriate for ESRD subjects treated with haemodialysis / haemodiafiltration as per local guidelines, which includes dietary potassium restriction.
Exclusion Criteria:
- Myocardial infarction, acute coronary syndrome, stroke, seizure or a thrombotic / thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism, but excluding vascular access thrombosis) within 12 weeks prior to randomization.
- Pseudohyperkalaemia secondary to haemolyzed blood specimen (this situation is not considered screening failure, sampling or full screening can be postponed to a later time as applicable).
- Diagnosis of rhabdomyolysis during the 4 weeks preceding randomization.
- Presence of cardiac arrhythmias or conduction defects that require immediate treatment.
- 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 subject in this study, which may confound safety or efficacy assessment and jeopardize the quality of the data, or may interfere with study participation.
- History of QT prolongation associated with other medications that required discontinuation of that medication; congenital long QT syndrome or QTc(f) > 550 msec; uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication or with transient atrial fibrillation associated with dialysis or peridialytic period are permitted.
- Subjects treated with sodium polystyrene sulfonate (e.g. SPS, Kayexalate, Resonium), calcium polystyrene sulfonate (CPS, Resonium calcium) or patiromer (Veltassa) within 7 days before screening or anticipated in requiring any of these agents during the study.
- Participation in another clinical study with an investigational product administered in the last 1 month before screening.
- Haemoglobin < 9 g/dL on screening (as assessed on Visit 1).
- Laboratory diagnosis of hypokalaemia (K < 3.5 mmol/L), hypocalcemia (Ca < 8.2 mg/d or albumin-corrected Ca < 8.0 mg/dL if the latter is used in local practice), hypomagnesemia (Mg < 1.7 mg/dL) or severe acidosis (serum bicarbonate 16 mEq/L or less) in the 4 weeks preceding randomization.
- Severe leukocytosis (> 20 × 109/L) or thrombocytosis (≥ 450 × 109/L) during screening.
- Polycythaemia (Hb > 14 g/dL) during screening.
- 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 subject should not participate in the study if the subject is unlikely to comply with study procedures, restrictions and requirements.
- Previous randomisation in the present study.
- For women only - currently pregnant (confirmed with positive pregnancy test or uterine ultrasound if pregnancy test is questionable) or breast-feeding.
- Females of childbearing potential, unless using contraception as detailed in the protocol or sexual abstinence.
- Lack of compliance with haemodialysis prescription (both number and duration of treatments) during the two-week period preceding screening (100% compliance required).
- Subjects unable to take investigational product drug mix.
- Scheduled date for living donor kidney transplant.
- Subjects with a life expectancy of less than 6 months.
- Known hypersensitivity or previous anaphylaxis to SZC or to components thereof.
- History of alcohol or drug abuse within 2 years prior to randomization.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Sodium Zirconium Cyclosilicate (SZC)
Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) Single dose contains from 1 to 3 sachets of SZC 5g depending on dose level assigned to a patient per non-dialysis days.
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Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) Single dose contains from 1 to 3 sachets of SZC 5g depending on dose level assigned to a patient per non-dialysis days.
Other Names:
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Placebo Comparator: Placebo
Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) Single dose contains from 1 to 3 sachets of Placebo depending on dose level assigned to a patient per non-dialysis days.
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Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) Single dose contains from 1 to 3 sachets of Placebo depending on dose level assigned to a patient per non-dialysis days.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Responders
Time Frame: Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks.
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A subject was considered to be a responder if, during the evaluation period, they maintained a pre-dialysis serum potassium (S-K) between 4.0 and 5.0 mmol/L on at least 3 out of 4 dialysis treatments following the long inter-dialytic interval (LIDI) and did not receive rescue therapy.
Subjects with no data during the evaluation period were classified as non-responders.
The S-K levels used for this analysis were based on the measurements obtained by the central laboratory.
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Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Pre-dialysis S-K Values After SIDI and LIDI Below or Equal to 5.5 mmol/L During Evaluation Period
Time Frame: Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks.
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Probability of maintaining maximum S-K value <= 5.5 mmol/L was evaluated.
Each subject's maximum pre-dialysis S-K at long inter-dialytic interval (LIDI) and short inter-dialytic interval (SIDI) visits during the evaluation period were categorised into <= 5.5 or > 5.5 mmol/L.
Missing S-K values including those omitted due to coinciding with rescue therapy use or records omitted that are not true LIDI (i.e.
records which do not occur >= 55 hours after the previous dialysis starting time) were imputed using multiple imputation (MI).
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Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks.
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Pre-dialysis S-K After LIDI Between 3.5 and 5.5 mmol/L During the Evaluation Period
Time Frame: Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks.
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Probability of all S-K values between 3.5 and 5.5 mmol/L was evaluated.
Subjects were categorised to either having all pre-dialysis LIDI values between 3.5 and 5.5 mmol/L during the evaluation period or not.
Missing S-K values including those omitted due to coinciding with rescue therapy use or records omitted that are not true LIDI (i.e.
records which do not occur >= 55 hours after the previous dialysis starting time) were imputed using multiple imputation (MI).
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Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks.
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Instances of Pre-dialysis S-K After LIDI Between 4.0 and 5.0 mmol/L During the Evaluation Period
Time Frame: Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks.
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The probability of maintaining instances of pre-dialysis S-K between 4.0 and 5.0 mmol/L (normokalaemia) was evaluated at each LIDI visit during the evaluation period, by categorisation of pre-dialysis S-K into values between 4.0 and 5.0 mmol/L or not.
Values coinciding with rescue therapy or not true LIDI (i.e.
records which do not occur >= 55 hours after the previous dialysis starting time) were excluded.
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Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks.
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Expected Number of Normokalaemic (S-K 4.0-5.0 mmol/L) Instances
Time Frame: Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks.
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The expected number of normokalemic instances is the sum of the probabilities of normokalaemic instance at each visit during the evaluation period.
Normokalaemic is defined as S-K between 4.0 and 5.0 mmol/L.
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Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks.
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Instances of Potassium Gradient of < 3.0 mmol/L After LIDI During the Evaluation Period
Time Frame: Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks.
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The probability of maintaining instances of potassium gradient of < 3.0 mmol/L was evaluated at each LIDI visit during the evaluation period, by categorisation of potassium gradient into < 3.0 or >=3.0 mmol/L.
Values coinciding with rescue therapy or not true LIDI (i.e.
records which do not occur >= 55 hours after the previous dialysis starting time) were excluded.
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Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks.
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Zhaohui Ni, Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, China.
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- D9485C00001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD 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
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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