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HyperkalemiaPhase 3DIALIZENCT03303521

A Study to Test Whether ZS (Sodium Zirconium Cyclosilicate) Can Reduce the Incidence of Increased Blood Potassium Levels Among Dialized Patients.

A Phase 3 study testing Sodium Zirconium Cyclosilicate (ZS) in people with Hyperkalemia, run by AstraZeneca at 53 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate the efficacy of ZS in the treatment of hyperkalemia in patients on hemodialysis. Read more about this study

Who is it for?
Ages 18 to 130 years
Conditions the study is for
Hyperkalemia
What is being tested?
Sodium Zirconium Cyclosilicate (ZS)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
196 participants
Where
53 sitesin 4 countries
Study dates
14 Dec 2017to 7 Nov 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 130 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Provision of informed consent prior to any study specific procedures
  • Female or male aged ≥ 18 years at screening Visit 1. For patients aged <20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative.
  • Receiving hemodialysis (or hemodiafiltration) 3 times a week for treatment of endstage renal disease (ESRD) for at least 3 months before randomization.
  • Patients must have hemodialysis access consisting of an arteriovenous fistula, AV graft, or tunneled (permanent) catheter which is expected to remain in place for the entire duration of the study.
  • Pre-dialysis serum K >5.4 mmol/L after long inter-dialytic interval and >5.0 mmol/L after one short inter-dialytic interval during screening (as assessed by central lab).
  • Prescribed dialysate K concentration ≤ 3 mmol/L during screening
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  • Sustained Qb ≥200 ml/min and spKt/V ≥1.2 (or URR ≥ 63) on stable hemodialysis/hemodiafltration prescription during screening with prescription (time, dialyzer, blood flow [Qb], dialysate flow rate [Qd] and bicarbonate concentration) expected to remain unchanged during study
  • Heparin dose (if used) must be stable during screening and expected to be stable during the study
  • Subjects must be receiving dietary counseling appropriate for ESRD patients treated with hemodialysis/hemodiafiltration as per local guidelines, which includes dietary potassium restriction.

Who cannot join

  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca, including ZS Pharma staff and/or staff at the study site)
  • Hemoglobin <9 g/dL on screening (as assessed on Visit 1)
  • Lack of compliance with hemodialysis prescription (both number and duration of treatments) during the two-week period preceding screening (100% compliance required)
  • Patients treated with sodium polystyrene sulfonate (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
  • 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
  • Laboratory diagnosis of hypokalemia (K < 3.5 mmol/L), hypocalcemia (Ca < 8.2 mg/dL; for Japan hypocalcemia is defined as albumin-corrected Ca < 8.0 mg/dL), hypomagnesemia (Mg < 1.7 mg/dL) or severe acidosis (serum bicarbonate 16 mEq/L or less) in the 4 weeks preceding randomization
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  • Pseudohyperkalemia secondary to hemolyzed blood specimen (this situation is not considered screening failure, sampling or full screening can be postponed to a later time as applicable).
  • Severe leukocytosis (>20× 10^9/L) or thrombocytosis (≥450 × 10^9/L) during screening
  • Polycythemia (Hb >14 g/dL) during screening
  • Diagnosis of rhabdomyolysis during the 4 weeks preceding randomization
  • Patients treated with lactulose, xifaxan (rifaximin) or other non-absorbed antibiotics for hyperammonemia within 7 days prior to the first dose of study drug
  • Patients unable to take oral ZS drug mix
  • Scheduled date for living donor kidney transplant
  • Patients with a life expectancy of less than 6 months
  • Female patients who are pregnant or breastfeeding
  • Females of childbearing potential, unless using contraception as detailed in the protocol or sexual abstinence.
  • Known hypersensitivity or previous anaphylaxis to ZS or to components thereof
  • Participation in another clinical study with an investigational product during the last 1 month before screening
  • Any medical condition, including active, clinically significant infection, that in the opinion of the investigator or Sponsor may pose a safety risk to a patient in this study, which may confound safety or efficacy assessment and jeopardize the quality of the data, or may interfere with study participation
  • Presence of cardiac arrhythmias or conduction defects that require immediate treatment
  • History of alcohol or drug abuse within 2 years prior to randomization
  • Previous randomization in the present study

Trial locations and contacts

53 sites in 4 countries.

53 sites in 4 countries

Japan16 sites

  • Research Site

    Hamamatsu, 432-8036

  • Research Site

    Kumamoto, 860-4112

  • Research Site

    Miyagi-gun, 981-0112

  • Research Site

    Nagano, 388-8004

  • Research Site

    Niigata, 950-2087

  • Research Site

    Ora-gun, 370-0615

  • Research Site

    Osaka, 543-0052

  • Research Site

    Sakaishi, 599-8272

  • Research Site

    Sashima-gun, 306-0433

  • Research Site

    Sendai, 980-0801

  • Research Site

    Shinjuku-ku, 169-0075

  • Research Site

    Toride-shi, 302-0022

  • Research Site

    Tsukuba, 305-0861

  • Research Site

    Wakayama, 640-8335

  • Research Site

    Yachiyo-shi, 276-0031

  • Research Site

    Yokosuka-shi, 238-0004

Other trials in Japan

United States15 sites

  • Research Site

    East Providence, Rhode Island, 02914

  • Research Site

    El Paso, Texas, 79924

  • Research Site

    Fresh Meadows, New York, 11365

  • Research Site

    Great Neck, New York, 11021

  • Research Site

    Houston, Texas, 77004

  • Research Site

    Kansas City, Missouri, 64108

  • Research Site

    Los Angeles, California, 90022

  • Research Site

    Los Angeles, California, 90025

  • Research Site

    Ontario, California, 91762

  • Research Site

    Paterson, New Jersey, 07504

  • Research Site

    Ridgewood, New York, 11385

  • Research Site

    San Dimas, California, 91773

  • Research Site

    St Louis, Missouri, 63110

  • Research Site

    The Bronx, New York, 10461

  • Research Site

    Whittier, California, 90606

Other trials in United States

Russia13 sites

  • Research Site

    Kemerovo, 650066

  • Research Site

    Kolomna

  • Research Site

    Moscow, 141007

  • Research Site

    Novosibirsk, 630087

  • Research Site

    Omsk, 644111

  • Research Site

    Penza, 440034

  • Research Site

    Podolsk

  • Research Site

    Rostov-on-Don, 344029

  • Research Site

    Saint Petersburg, 191104

  • Research Site

    Saint Petersburg, 196247

  • Research Site

    Saint Petersburg, 198205

  • Research Site

    Yaroslavl, 150062

  • Research Site

    Yekaterinburg, 620102

Other trials in Russia

United Kingdom9 sites

  • Research Site

    Cardiff, CF14 4XW

  • Research Site

    Hull, HU3 2JZ

  • Research Site

    Leicester, LE5 4PW

  • Research Site

    London, EC1A 7BE

  • Research Site

    London, SE5 9RS

  • Research Site

    London, SM5 1AA

  • Research Site

    London, SW17 0QT

  • Research Site

    Swansea, SA6 6NL

  • Research Site

    York, YO31 8HE

Other trials in United Kingdom

About this study

Official title: A Phase 3b, Multicenter, Prospective, Randomized, Double Blind, Placebocontrolled Study to Reduce Incidence of Pre-dialysis Hyperkalemia With Sodium Zirconium Cyclosilicate (DIALIZE)

The purpose of this study is to evaluate the efficacy of ZS in the treatment of hyperkalemia in patients on hemodialysis.

Conditions
Hyperkalemia
Being tested
Placebo, Sodium Zirconium Cyclosilicate (ZS)
Medical subject headings
Hyperkalemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlaceboDrug

    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.

  • Sodium Zirconium Cyclosilicate (ZS)Drug

    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 ZS 5g depending on dose level assigned to a patient per non-dialysis days.

Study groups in NCT03303521
Study groupRoleWhat they receive
Sodium Zirconium Cyclosilicate (ZS)ExperimentalSuspension 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 ZS 5g depending on dose level assigned to a patient per non-dialysis days.
Receives: Drug: Sodium Zirconium Cyclosilicate (ZS)
PlaceboPlacebo comparatorSuspension 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Responders

    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 and did not receive rescue therapy. The S-K levels used for this analysis were based on the measurements obtained by the central laboratory.

    Measured: Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks, starting after visit 11 and ending on visit 15, thus it comprises post-long inter-dialytic interval visits 12, 13, 14 and 15.

  2. Percentage of Responders When Accounting for Missing Central Laboratory Serum Potassium Data

    The sensitivity analysis assessed the impact of subjects classified as non-responders due to missing serum potassium (S-K) data. Missing central lab (c-lab) pre-dialysis values were imputed using corresponding pre-dialysis i-STAT (a portable blood analyser) measurements. In addition, a "last observation carried forward" (LOCF) approach was utilized to further impute missing values of pre-dialysis S-K during the evaluation period. This technique will replace missing c-lab S-K values with the last available non-missing pre-dialysis LIDI observation recorded for that patient (and this could be a c-lab value or an imputed c-lab value). The Primary endpoint analysis was repeated on the imputed data.

    Measured: Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks, starting after visit 11 and ending on visit 15, thus it comprises post-long inter-dialytic interval visits 12, 13, 14 and 15.

Secondary outcomes (1)

  1. Percentage of Patients Needing Rescue Therapy

    Patients requiring any urgent intervention consistent with local practice patterns to reduce serum potassium (S-K) including insulin/glucose, beta-adrenergic agonists, sodium bicarbonate, K binders or any form of renal replacement therapy.

    Measured: An 8 week overall treatment period (a 4 week adjustment phase plus a 4 week evaluation phase) and a 2 week follow up period.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Oct 2017
  2. Study start14 Dec 2017
  3. Primary completion7 Nov 2018
  4. Study completion7 Nov 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
196 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03303521
Sponsor's protocol ID
D9480C00006
Other IDs
2017-003029-14, 2017
Acronym
DIALIZE
Status last verified
Feb 2020
First submitted
26 Sep 2017
Last updated
20 Feb 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Fishbane S, Ford M, Fukagawa M, McCafferty K, Rastogi A, Spinowitz B, Staroselskiy K, Vishnevskiy K, Lisovskaja V, Al-Shurbaji A, Guzman N, Bhandari S. Potassium responses to sodium zirconium cyclosilicate in hyperkalemic hemodialysis patients: post-hoc analysis of DIALIZE. BMC Nephrol. 2022 Feb 8;23(1):59. doi: 10.1186/s12882-021-02569-7.

    PubMed 35135481

  • Natale P, Palmer SC, Ruospo M, Saglimbene VM, Strippoli GF. Potassium binders for chronic hyperkalaemia in people with chronic kidney disease. Cochrane Database Syst Rev. 2020 Jun 26;6(6):CD013165. doi: 10.1002/14651858.CD013165.pub2.

    PubMed 32588430

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Sodium Zirconium Cyclosilicate (ZS) in people with Hyperkalemia, run by AstraZeneca at 53 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 53 sites in Japan, United States, Russia, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Responders (time frame: Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks, starting after visit 11 and ending on visit 15, thus it comprises post-long inter-dialytic interval visits 12, 13, 14 and 15.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03303521, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2020; AzTrials last refreshed its copy on 30 Oct 2026.

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