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TerminatedNCT04727528NEUTRALIZEUpdated Oct 6, 2023Results posted

Study of the Effect of SZC on Serum Potassium and Serum Bicarbonate in Patients With Hyperkalemia and Metabolic Acidosis Associated With Chronic Kidney Disease

A Phase 3 interventional study of Sodium zirconium cyclosilicate and Placebo in Hyperkalaemia, Metabolic Acidosis and Chronic Kidney Disease, sponsored by AstraZeneca. Terminated at 30 sites in 2 countries. Open to participants aged 18 Years to 130 Years. Per ClinicalTrials.gov, last updated 2023-10-06.

Sponsored by AstraZeneca · Phase 3, Interventional, and Treatment

Why this study was terminated
The study was stopped due to a higher than expected screen fail rate (83%) which lead to very low patient enrollment into the study. It should be noted that the decision to terminate the study is not related to safety concerns.
Phase
Phase 3
Study type
Interventional
Enrollment
39
Allocation
Randomized
Ages
18 Years to 130 Years
Sex
All
01

Study summary

The main objective of this study is to evaluate the efficacy of SZC as compared to placebo in maintaining normal sK+ in patients with hyperkalemia and metabolic acidosis associated with CKD

Read the detailed description

NEUTRALIZE is a prospective, randomized, double-blind, placebo-controlled, parallel, multicenter, Phase IIIb study to investigate the safety and efficacy of SZC in patients with hyperkalemia and low bicarbonate (metabolic acidosis ).

The study will be conducted in the United States (US) at approximately 35 investigative sites.

After screening on Day 1, all eligible patients will receive open-label SZC for up to 48 hours. Patients who achieve normokalemia within 48 hours will be randomized 1:1 into the double-blind randomized treatment phase to receive SZC or placebo. Study treatment will end with the Day 29 visit, which will be followed by a follow-up visit 7 days after the last administration of study medication.

02

Conditions studied

  • Hyperkalaemia
  • Metabolic Acidosis
  • Chronic Kidney Disease
03

In context

Kidney Diseases

3,840 studies on the registry are indexed under Kidney Diseases; 500 are open to participants now.

This study's enrollment of 39 is below the median of 70 across 2,640 interventional studies indexed under Kidney Diseases.

Browse Kidney Diseases studies →

Lead sponsor

AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.

Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 130 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Adults aged ≥18 years
  • Participants who have CKD stage 3-5, not on dialysis.
  • POCT K+ level >5 mmol/L to ≤5.9 mmol/L and POCT bicarbonate levels between 16-20 mmol/L inclusive prior to the first SZC dose on study Day 1
  • Ability to have repeated blood draws or effective venous catheterization.
  • Male and/or female. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • Capable of giving signed informed consent

Exclusion criteria

Exclusion Criteria:

  • Participants with pseudohyperkalemia.
  • Dialysis requirement or anticipated by the investigator to require dialysis therapy within 1 month, history of renal transplant, or life expectancy less than 3 months.
  • Cardiac arrhythmias requiring immediate treatment.
  • Active or suspected diabetic ketoacidosis.
  • POCT bicarbonate low enough to need emergency intervention or treatment as judged by the investigator.
  • Acute/chronic worsening renal function (eg, ≥30% decline in eGFR) in the 3 months before screening.
  • Current acute decompensated HF, hospitalization due to decompensated HF within 4 weeks prior to screening, or myocardial infarction (MI), unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to screening.
  • Coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or valvular repair/replacement within 12 weeks prior to screening or planned to undergo any of these operations.
  • Symptomatic hypotension.
  • Current exacerbation of chronic obstructive pulmonary disease (COPD)/asthma or hospitalization due to exacerbation of COPD/asthma within 4 weeks of screening.
  • Severe constipation, bowel obstruction or impaction, including abnormal post-operative bowel motility disorders
  • Active malignancy requiring treatment.
  • History of QT prolongation associated with other medications that required discontinuation of that medication.
  • Congenital long QT syndrome.
  • Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Patients with atrial fibrillation controlled by medication are permitted.
  • QTcF (QT interval corrected by the Fridericia method) >550 msec.
  • Active treatment (within 7 days prior to screening) with SZC, sodium bicarbonate, sodium polystyrene sulfonate, lactulose, or patiromer
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
39 participants (actual)

Study arms

  • Experimental
    Open-label correction phase (up to 48 hours)

    All eligible patients will receive SZC 10 g TID for up to 48 hours. Patients with POCT (Point-of-Care-Test) K+ ≥5.1 mmol/L after 24 hours will continue on SZC 10 g TID for another 24 hours. Patients who achieve normokalemia (defined as POCT K+ between 3.5 and 5.0 mmol/L inclusive) after receiving SZC 10 g TID for up to 48 hours will proceed to randomization. Patients with POCT K+ \<3.5mmol/L at any time during the open-label phase will be withdrawn from study treatment and will be followed per protocol.

    Drug: Sodium zirconium cyclosilicate · Drug: Placebo

  • Experimental
    Randomized, placebo controlled phase (Day 2 or 3 to Day 29)

    Patients will be randomized to SZC 10 g QD or placebo 10 g QD. The dose of SZC/placebo will be titrated by increasing or decreasing the dose by 5 g increments at 1-week intervals to between 5 g every other day (QOD) and 15 g QD of the randomized phase to maintain normokalemia by POCT K+.

    Drug: Sodium zirconium cyclosilicate · Drug: Placebo

Interventions

  • DrugSodium zirconium cyclosilicate

    Investigational medicinal product

    Also known as: SZC

  • DrugPlacebo

    Plabeco comparator

06

What researchers measure

Primary outcomes

  1. Occurrence (Yes/no) of Participants Having Normal Serum Potassium (sK+) Between 3.5 and 5.0 mmol/L Inclusive at End of Treatment (EOT) Without Need for Rescue Treatment for Hyperkalemia at Any Point During the Randomized Phase

    Response was defined as a subject having serum potassium (sK+) within 3.5-5.0 mmol/L at the EOT visit, and no use of rescue therapy for hyperkalaemia at any point during the randomized placebo-controlled period. Participants who used rescue therapy for hyperkalaemia at any point during the randomized placebo-controlled period were assigned a non-response. Participants who died prior to the EOT visit were treated as non-response. Participants who were lost to follow-up prior to the EOT visit had response treated as missing.

    Time frame: Day 1 of randomization phase to Day 29

Secondary outcomes

  1. Mean Serum Bicarbonate at Day 29

    Least-squares mean calculated with a repeated measures analysis of covariance model where the dependent variable was post randomization serum bicarbonate and with fixed terms for randomized treatment group and serum bicarbonate.

    Time frame: Day 29

  2. Occurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 3 mmol/L From Baseline to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate)

    Occurrence (yes/no) of participants having an increase in serum bicarbonate of greater than or equal to 3 mmol/L from baseline (Day 1) to EOT (Day 29) without need for rescue treatment for metabolic acidosis (low bicarbonate). Response was defined as a participant with an increase in serum bicarbonate greater than or equal to 3 mmol/L at the EOT visit without the need for rescue therapy for low bicarbonate. Participants who used rescue therapy for low bicarbonate at any point during the randomized placebo-controlled period had their last observation prior to rescue therapy carried forward. Participants who were lost to follow-up prior to the EOT visit had response treated as missing. Logistic regression model included response status (response / non-response) as the dependent variable and randomized treatment as an independent factor. Participants who died prior to the EOT visit were assigned a non-response.

    Time frame: Day 1 to Day 29 of randomization phase

  3. Occurrence (Yes/no) of Participants Having Serum Bicarbonate ≥22 mmol/L

    Response was defined as a participant with an increase in serum bicarbonate greater than or equal to 22 mmol/L at the EOT visit without the need for rescue therapy for low bicarbonate. Participants who had used rescue therapy for low bicarbonate at any point during the randomized placebo-controlled period had their last observation prior to rescue therapy carried forward. Participants who died prior to the EOT visit were assigned a non-response. Participants who were lost to follow-up prior to the EOT visit had response treated as missing. Logistic regression model included response status (response / non-response) as the dependent variable and randomized treatment as an independent factor.

    Time frame: Day 1 to Day 29 of randomization phase

  4. Occurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 2 mmol/L From Baseline (Day 1) to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate)

    Response was defined as a participant with an increase in serum bicarbonate greater than or equal to 2 mmol/L at the EOT visit and no use of rescue therapy for low bicarbonate at any point during the randomized placebo-controlled period. Participants who used rescue therapy for low bicarbonate at any point during the randomized placebo-controlled period had their last observation prior to rescue therapy carried forward. Participants who were lost to follow-up prior to the EOT visit had response treated as missing. Logistic regression model included response status (response / non-response) as the dependent variable and randomized treatment as an independent factor. Participants who died prior to the EOT visit were assigned a non-response.

    Time frame: Day 1 to Day 29 of randomization phase

  5. Participants Having Normal sK+ at EOT and an Increase in Serum Bicarbonate of ≥3 mmol/L From Baseline Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) or Hyperkalemia

    Participants with normal sK+ between 3.5 and 5.0 mmol/L inclusive at EOT and increase in serum bicarbonate greater than or equal to 3 mmol/L from Day 1 without rescue treatment for metabolic acidosis (low bicarbonate) or hyperkalemia. Response was a participant with sK+ within 3.5-5.0 mmol/L and increase in serum bicarbonate greater than or equal to 3 mmol/L at the EOT visit and no use of rescue therapy for hyperkalaemia or low bicarbonate at any point during the randomized placebo-controlled period. Participants who used rescue therapy for low bicarbonate or HK during the randomized placebo-controlled period had last observation prior to rescue therapy carried forward. Participants lost to follow-up prior to EOT visit had response as missing. Logistic regression model included response status (response/non-response) as dependent variable and randomized treatment as an independent factor. Participants who died prior to the EOT visit were assigned a non-response.

    Time frame: Day 1 to Day 29 of randomization phase

  6. Occurrence (Yes/no) of Patients Having a Normal sK+ Between 3.5 and 5.0 mmol/L Inclusive and Bicarbonate ≥22 mmol/L at Day 29 Without Need for Rescue Treatment for Hyperkalemia or Metabolic Acidosis (Low Bicarbonate)

    Response was defined as a participant with sK+ within 3.5-5.0 mmol/L and serum bicarbonate greater than or equal to 22 mmol/L at the EOT visit without the need for rescue therapy for hyperkalaemia or low bicarbonate. Participants who used rescue therapy for hyperkalaemia or low bicarbonate at any point during the randomized placebo-controlled period were assigned a non-response. Participants who were lost to follow-up prior to the EOT visit had response treated as missing. Logistic regression model included response status (response / non-response) as the dependent variable and randomized treatment as an independent factor. Participants who died prior to the EOT visit were assigned a non-response.

    Time frame: Day 1 to Day 29 of randomization phase

  7. Occurrence (Yes/no) of Participants Needing Rescue Treatment for Low Sodium Bicarbonate

    Occurrence (yes/no) of participants needing rescue treatment for low sodium bicarbonate any time during the randomized phase

    Time frame: Day 1 to Day 29 of randomization phase

07

Results

Posted Oct 6, 2023
Limitations and caveats
Due to a screening failure rate higher than expected which led to early termination of the study, only 39 (17.0%) patients entered the open-label phase. Due to the early termination of the study and small sample size, the study was underpowered for the secondary efficacy endpoints.

Participant flow

Open-label Period
Participant flow — Open-label Period
MilestoneSodium Zirconium Cyclosilicate (SZC)Placebo
Started390
Completed370
Not completed20
Withdrew: Did not meet randomization criteria for double-blind treatment phase10
Withdrew: Randomized who did not receive treatment10
Double-blind Treatment Phase
Participant flow — Double-blind Treatment Phase
MilestoneSodium Zirconium Cyclosilicate (SZC)Placebo
Started1720
Completed1615
Not completed15
Withdrew: Adverse event01
Withdrew: Death01
Withdrew: Missed doses whilst in hospital01
Withdrew: Investigator decision to start rescue therapy for hyperkalemia01
Withdrew: Physician decision01
Withdrew: Withdrawal by subject10

Outcome measures

PrimaryOccurrence (Yes/no) of Participants Having Normal Serum Potassium (sK+) Between 3.5 and 5.0 mmol/L Inclusive at End of Treatment (EOT) Without Need for Rescue Treatment for Hyperkalemia at Any Point During the Randomized Phase

Response was defined as a subject having serum potassium (sK+) within 3.5-5.0 mmol/L at the EOT visit, and no use of rescue therapy for hyperkalaemia at any point during the randomized placebo-controlled period. Participants who used rescue therapy for hyperkalaemia at any point during the randomized placebo-controlled period were assigned a non-response. Participants who died prior to the EOT visit were treated as non-response. Participants who were lost to follow-up prior to the EOT visit had response treated as missing.

Time frame:
Day 1 of randomization phase to Day 29
Reported as:
Count of participants · Participants
Occurrence (Yes/no) of Participants Having Normal Serum Potassium (sK+) Between 3.5 and 5.0 mmol/L Inclusive at End of Treatment (EOT) Without Need for Rescue Treatment for Hyperkalemia at Any Point During the Randomized Phase
ParticipantsSodium Zirconium Cyclosilicate (SZC)Placebo
No response115
Response154
Missing11
Statistical analysis
  • Sodium Zirconium Cyclosilicate (SZC) vs Placebo · Wald Chi-Squared test · p = 0.001 · Odds ratio (or): 56.2 · 95% CI 5.6 to 563.6Logistic regression model included response status (response / non-response) as the dependent variable and randomized treatment as an independent factor.
SecondaryMean Serum Bicarbonate at Day 29

Least-squares mean calculated with a repeated measures analysis of covariance model where the dependent variable was post randomization serum bicarbonate and with fixed terms for randomized treatment group and serum bicarbonate.

Time frame:
Day 29
Reported as:
Least squares mean · mmol/L
Mean Serum Bicarbonate at Day 29
mmol/LSodium Zirconium Cyclosilicate (SZC)Placebo
Mean Serum Bicarbonate at Day 2918.17 ± 0.5816.52 ± 0.56
Statistical analysis
  • Sodium Zirconium Cyclosilicate (SZC) vs Placebo · t-test, 2 sided · p = 0.050 · Least-squares mean: 1.64 · 95% CI -0.00 to 3.29
SecondaryOccurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 3 mmol/L From Baseline to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate)

Occurrence (yes/no) of participants having an increase in serum bicarbonate of greater than or equal to 3 mmol/L from baseline (Day 1) to EOT (Day 29) without need for rescue treatment for metabolic acidosis (low bicarbonate). Response was defined as a participant with an increase in serum bicarbonate greater than or equal to 3 mmol/L at the EOT visit without the need for rescue therapy for low bicarbonate. Participants who used rescue therapy for low bicarbonate at any point during the randomized placebo-controlled period had their last observation prior to rescue therapy carried forward. Participants who were lost to follow-up prior to the EOT visit had response treated as missing. Logistic regression model included response status (response / non-response) as the dependent variable and randomized treatment as an independent factor. Participants who died prior to the EOT visit were assigned a non-response.

Time frame:
Day 1 to Day 29 of randomization phase
Reported as:
Count of participants · Participants
Occurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 3 mmol/L From Baseline to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate)
ParticipantsSodium Zirconium Cyclosilicate (SZC)Placebo
No response1016
Response63
Missing11
Statistical analysis
  • Sodium Zirconium Cyclosilicate (SZC) vs Placebo · Wald Chi-Squared test · p = 0.153 · Odds ratio (or): 3.2 · 95% CI 0.6 to 15.8
SecondaryOccurrence (Yes/no) of Participants Having Serum Bicarbonate ≥22 mmol/L

Response was defined as a participant with an increase in serum bicarbonate greater than or equal to 22 mmol/L at the EOT visit without the need for rescue therapy for low bicarbonate. Participants who had used rescue therapy for low bicarbonate at any point during the randomized placebo-controlled period had their last observation prior to rescue therapy carried forward. Participants who died prior to the EOT visit were assigned a non-response. Participants who were lost to follow-up prior to the EOT visit had response treated as missing. Logistic regression model included response status (response / non-response) as the dependent variable and randomized treatment as an independent factor.

Time frame:
Day 1 to Day 29 of randomization phase
Reported as:
Count of participants · Participants
Occurrence (Yes/no) of Participants Having Serum Bicarbonate ≥22 mmol/L
ParticipantsSodium Zirconium Cyclosilicate (SZC)Placebo
No response1419
Response20
Missing11
Statistical analysis
  • Sodium Zirconium Cyclosilicate (SZC) vs Placebo · Wald Chi-Squared test · p = 0.940 · Odds ratio (or): 57008.6
SecondaryOccurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 2 mmol/L From Baseline (Day 1) to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate)

Response was defined as a participant with an increase in serum bicarbonate greater than or equal to 2 mmol/L at the EOT visit and no use of rescue therapy for low bicarbonate at any point during the randomized placebo-controlled period. Participants who used rescue therapy for low bicarbonate at any point during the randomized placebo-controlled period had their last observation prior to rescue therapy carried forward. Participants who were lost to follow-up prior to the EOT visit had response treated as missing. Logistic regression model included response status (response / non-response) as the dependent variable and randomized treatment as an independent factor. Participants who died prior to the EOT visit were assigned a non-response.

Time frame:
Day 1 to Day 29 of randomization phase
Reported as:
Count of participants · Participants
Occurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 2 mmol/L From Baseline (Day 1) to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate)
ParticipantsSodium Zirconium Cyclosilicate (SZC)Placebo
No response813
Response86
Missing11
Statistical analysis
  • Sodium Zirconium Cyclosilicate (SZC) vs Placebo · Wald Chi-Squared test · p = 0.271 · Odds ratio (or): 2.2 · 95% CI 0.5 to 8.6
SecondaryParticipants Having Normal sK+ at EOT and an Increase in Serum Bicarbonate of ≥3 mmol/L From Baseline Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) or Hyperkalemia

Participants with normal sK+ between 3.5 and 5.0 mmol/L inclusive at EOT and increase in serum bicarbonate greater than or equal to 3 mmol/L from Day 1 without rescue treatment for metabolic acidosis (low bicarbonate) or hyperkalemia. Response was a participant with sK+ within 3.5-5.0 mmol/L and increase in serum bicarbonate greater than or equal to 3 mmol/L at the EOT visit and no use of rescue therapy for hyperkalaemia or low bicarbonate at any point during the randomized placebo-controlled period. Participants who used rescue therapy for low bicarbonate or HK during the randomized placebo-controlled period had last observation prior to rescue therapy carried forward. Participants lost to follow-up prior to EOT visit had response as missing. Logistic regression model included response status (response/non-response) as dependent variable and randomized treatment as an independent factor. Participants who died prior to the EOT visit were assigned a non-response.

Time frame:
Day 1 to Day 29 of randomization phase
Reported as:
Count of participants · Participants
Participants Having Normal sK+ at EOT and an Increase in Serum Bicarbonate of ≥3 mmol/L From Baseline Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) or Hyperkalemia
ParticipantsSodium Zirconium Cyclosilicate (SZC)Placebo
No response1018
Response61
Missing11
Statistical analysis
  • Sodium Zirconium Cyclosilicate (SZC) vs Placebo · Wald Chi-Squared test · p = 0.039 · Odds ratio (or): 10.8 · 95% CI 1.1 to 102.8
SecondaryOccurrence (Yes/no) of Patients Having a Normal sK+ Between 3.5 and 5.0 mmol/L Inclusive and Bicarbonate ≥22 mmol/L at Day 29 Without Need for Rescue Treatment for Hyperkalemia or Metabolic Acidosis (Low Bicarbonate)

Response was defined as a participant with sK+ within 3.5-5.0 mmol/L and serum bicarbonate greater than or equal to 22 mmol/L at the EOT visit without the need for rescue therapy for hyperkalaemia or low bicarbonate. Participants who used rescue therapy for hyperkalaemia or low bicarbonate at any point during the randomized placebo-controlled period were assigned a non-response. Participants who were lost to follow-up prior to the EOT visit had response treated as missing. Logistic regression model included response status (response / non-response) as the dependent variable and randomized treatment as an independent factor. Participants who died prior to the EOT visit were assigned a non-response.

Time frame:
Day 1 to Day 29 of randomization phase
Reported as:
Count of participants · Participants
Occurrence (Yes/no) of Patients Having a Normal sK+ Between 3.5 and 5.0 mmol/L Inclusive and Bicarbonate ≥22 mmol/L at Day 29 Without Need for Rescue Treatment for Hyperkalemia or Metabolic Acidosis (Low Bicarbonate)
ParticipantsSodium Zirconium Cyclosilicate (SZC)Placebo
No response1419
Response20
Missing11
Statistical analysis
  • Sodium Zirconium Cyclosilicate (SZC) vs Placebo · Wald Chi-Squared test · p = 0.940 · Odds ratio (or): 57008.6
SecondaryOccurrence (Yes/no) of Participants Needing Rescue Treatment for Low Sodium Bicarbonate

Occurrence (yes/no) of participants needing rescue treatment for low sodium bicarbonate any time during the randomized phase

Time frame:
Day 1 to Day 29 of randomization phase
Reported as:
Count of participants · Participants
Occurrence (Yes/no) of Participants Needing Rescue Treatment for Low Sodium Bicarbonate
ParticipantsSodium Zirconium Cyclosilicate (SZC)Placebo
Rescue treatment required00
Rescue treatment not required1720

Adverse events

Collected over Adverse events were collected at screening, during the open-label correction phase (Days 1 and 2), throughout the treatment period of the the randomization phase (Days 2 or 3 to 29 or 30 [end of treatment] or discontinuation), and during the follow up phase (Day 36 to 39).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Open-Label Phase0/38 (0%)0/38 (0%)1/38 (2.6%)
Sodium Zirconium Cyclosilicate (SZC) Double-blind Treatment Phase0/17 (0%)1/17 (5.9%)4/17 (23.5%)
Placebo Double-blind Treatment Phase1/20 (5%)2/20 (10%)9/20 (45%)
Most frequent serious events
Most frequent serious events
EventOpen-Label PhaseSodium Zirconium Cyclosilicate (SZC) Double-blind Treatment PhasePlacebo Double-blind Treatment Phase
HypertensionVascular disorders0/381/170/20
HypervolaemiaMetabolism and nutrition disorders0/380/171/20
Acute kidney injuryRenal and urinary disorders0/380/171/20
Most frequent other events
Showing 10 of 23
Most frequent other events
EventOpen-Label PhaseSodium Zirconium Cyclosilicate (SZC) Double-blind Treatment PhasePlacebo Double-blind Treatment Phase
HyperkalaemiaMetabolism and nutrition disorders0/380/174/20
NauseaGastrointestinal disorders0/380/172/20
Peripheral swellingGeneral disorders0/381/170/20
COVID-19Infections and infestations0/381/170/20
HeadacheNervous system disorders0/381/170/20
TinnitusEar and labyrinth disorders0/381/170/20
Vision blurredEye disorders0/381/170/20
Vitreous floatersEye disorders0/381/170/20
DiarrhoeaGastrointestinal disorders1/380/171/20
Oedema peripheralGeneral disorders0/380/171/20

Baseline characteristics

Full analysis set

Age, Continuous
Age, Continuous(years)Sodium Zirconium Cyclosilicate (SZC)PlaceboTotal
Mean60.3 ± 16.7765.9 ± 11.1363.3 ± 14.09
Age, Customized
Age, Customized(Participants)Sodium Zirconium Cyclosilicate (SZC)PlaceboTotal
>=85000
18-649918
65-8481119
Sex: Female, Male
Sex: Female, Male(Participants)Sodium Zirconium Cyclosilicate (SZC)PlaceboTotal
Female4812
Male131225
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Sodium Zirconium Cyclosilicate (SZC)PlaceboTotal
Hispanic or Latino6410
Not Hispanic or Latino111627
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Sodium Zirconium Cyclosilicate (SZC)PlaceboTotal
American Indian or Alaskan Native000
Asian000
Black or African American314
Native Hawaiian or Other Pacific Islander000
Other011
White141832
Diabetes status
Diabetes status(Participants)Sodium Zirconium Cyclosilicate (SZC)PlaceboTotal
No6511
Yes111526
Chronic Kidney Disease (CKD) Status
Chronic Kidney Disease (CKD) Status(Participants)Sodium Zirconium Cyclosilicate (SZC)PlaceboTotal
Stage 3134
Stage 414822
Stage 5167
Missing134
Chronic Heart Failure Status
Chronic Heart Failure Status(Participants)Sodium Zirconium Cyclosilicate (SZC)PlaceboTotal
No172037
Yes000
08

Study locations

30 sites
  • Research Site
    Florence, Alabama 35630, United States
  • Research Site
    Chula Vista, California 91910, United States
  • Research Site
    Downey, California 90242, United States
  • Research Site
    El Centro, California 92243, United States
  • Research Site
    S. Gate, California 90280, United States
  • Research Site
    Victorville, California 92395, United States
  • Research Site
    Aurora, Colorado 80045, United States
  • Research Site
    Denver, Colorado 80230, United States
  • Research Site
    Coral Gables, Florida 33134, United States
  • Research Site
    Columbus, Georgia 31904, United States
  • Research Site
    Hinsdale, Illinois 60521, United States
  • Research Site
    Kansas City, Missouri 64111, United States
  • Research Site
    Las Vegas, Nevada 89128, United States
  • Research Site
    Bronx, New York 10461, United States
  • Research Site
    Asheville, North Carolina 28801, United States
  • Research Site
    New Bern, North Carolina 28562, United States
  • Research Site
    Winston-Salem, North Carolina 27103, United States
  • Research Site
    Providence, Rhode Island 02903, United States
  • Research Site
    Spartanburg, South Carolina 29306, United States
  • Research Site
    Chattanooga, Tennessee 37404, United States
  • Research Site
    Memphis, Tennessee 38163, United States
  • Research Site
    Dallas, Texas 75230, United States
  • Research Site
    Dallas, Texas 75246, United States
  • Research Site
    San Antonio, Texas 78258, United States
  • Research Site
    Shenandoah, Texas 77384, United States
  • Research Site
    Alexandria, Virginia 22304, United States
  • Research Site
    Norfolk, Virginia 23510, United States
  • Research Site
    Bellevue, Washington 98004, United States
  • Research Site
    Milwaukee, Wisconsin 53226, United States
  • Research Site
    San Juan, 00918, Puerto Rico
09

References and documents

Study documents

  • Study protocol · Mar 3, 2022
  • Statistical analysis plan · Dec 1, 2022

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 6, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04727528
Lead sponsor
AstraZeneca
Responsible party
Sponsor
First posted
Jan 27, 2021
Start date
Mar 22, 2021
Primary completion
Sep 14, 2022
Completion
Sep 14, 2022
Results posted
Oct 6, 2023
Last update
Oct 6, 2023

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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