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HyperkalemiaPhase 3HARMONIZE AsiaNCT03528681

A Study to Investigate the Safety and Efficacy of ZS in Patients With Hyperkalemia.

A Phase 3 study testing Sodium Zirconium Cyclosilicate 5g and Sodium Zirconium Cyclosilicate 10g in people with Hyperkalemia, run by AstraZeneca at 66 sites in 2 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

To evaluate the efficacy of two different doses (5 and 10 g) of ZS orally administered once daily (qd) vs placebo in maintaining normokalemia in initially hyperkalemic patients having achieved normokalemia following 24 or 48 hours of initial ZS therapy (10g TID). Read more about this study

Who is it for?
Ages 18 to 90 years
Conditions the study is for
Hyperkalemia
What is being tested?
Sodium Zirconium Cyclosilicate 5g and Sodium Zirconium Cyclosilicate 10g
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
270 participants
Where
66 sitesin 2 countries
Study dates
6 May 2021to 15 Sep 2022
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 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Provision of informed consent (pre-screening consent) prior to any study specific procedures
  • Female and male patients aged ≥18 and ≤ 90 years
  • Provision of informed consent prior to any study specific procedures
  • Two consecutive i-STAT potassium values, measured 60 minutes (± 10 minutes) apart, both ≥ 5.1 mmol/L and measured within 1 day of the first ZS dose on open-label initial phase Day 1
  • Ability to have repeated blood draws or effective venous catheterization
  • Female patients must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception for the duration of the study (from the time they sign consent) and for 3 months after the last dose of ZS/matching placebo to prevent pregnancy. In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used

Who cannot join

  • Involvement in the planning and/or conduct of the study
  • Participation in another clinical study with an investigational product during the last 3 months
  • Presence of any condition which, in the opinion of the investigator, places the patient at undue risk or potentially jeopardizes the quality of the data to be generated
  • Pseudohyperkalemia signs and symptoms, such as hemolyzed blood specimen due to excessive fist clenching to make veins prominent, difficult or traumatic venepuncture, or history of severe leukocytosis or thrombocytosis
  • 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 treated with resins,calcium acetate,calcium carbonate, or lanthanum carbonate,within 7 days prior to the first dose of study drug
Show all 19Show fewer
  • Patients with a life expectancy of less than 3 months
  • Patients who are severely physically or mentally incapacitated and who in the opinion of investigator are unable to perform the subjects' tasks associated with the protocol
  • Female patients who are pregnant, lactating, or planning to become pregnant
  • Patients with diabetic ketoacidosis
  • Known hypersensitivity or previous anaphylaxis to ZS or to components thereof
  • Patients with cardiac arrhythmias that require immediate 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. Subjects with atrial fibrillation controlled by medication are permitted
  • QTc(f) > 550 msec
  • Patients on dialysis
  • Patients who are blood donors should not donate blood during the study and for 3 months following their last dose of ZS
  • Patients who need hospitalization after taking blood samples on day 1 of the open-label initial phase

Trial locations and contacts

66 sites in 2 countries.

66 sites in 2 countries

China52 sites

  • Research Site

    Baotou, 14010

  • Research Site

    Beijing, 100029

  • Research Site

    Beijing, 100144

  • Research Site

    Beijing, 100853

  • Research Site

    Beijing, 102206

  • Research Site

    Bengbu, 233004

  • Research Site

    Changchun, 130021

  • Research Site

    Changsha, 410008

  • Research Site

    Changsha, 430033

  • Research Site

    Chengdu, 610041

  • Research Site

    Chengdu, 610072

  • Research Site

    Dalian, 116027

  • Research Site

    Dongguan, 523009

  • Research Site

    Fuzhou, 350005

  • Research Site

    Fuzhou, 350025

  • Research Site

    Guangzhou, 510080

  • Research Site

    Guangzhou, 510120

  • Research Site

    Guiyang, 550004

  • Research Site

    Haikou, 570311

  • Research Site

    Hangzhou, 310003

  • Research Site

    Hangzhou, 310009

  • Research Site

    Hefei, 230022

  • Research Site

    Hefei, 230601

  • Research Site

    Jilin City, 132011

  • Research Site

    Jinan, 250021

  • Research Site

    Jingzhou, 434020

  • Research Site

    Kunming, 650011

  • Research Site

    Kunming, 650021

  • Research Site

    Lanzhou, 730030

  • Research Site

    Nanchang, 330006

  • Research Site

    Ningbo, 315010

  • Research Site

    Qingdao, 266000

  • Research Site

    Shanghai, 200025

  • Research Site

    Shanghai, 200090

  • Research Site

    Shanghai, 200127

  • Research Site

    Suzhou, 215006

  • Research Site

    Taiyuan, 030001

  • Research Site

    Taiyuan, 030012

  • Research Site

    Tianjin, 300121

  • Research Site

    Tianjin, 300211

  • Research Site

    Wuhan, 430030

  • Research Site

    Wuhan, 430070

  • Research Site

    Wuxi, 214023

  • Research Site

    Xi'an, 710061

  • Research Site

    Xiamen, 361003

  • Research Site

    Xining, 810001

  • Research Site

    Xining, 810007

  • Research Site

    Yangzhou, 225001

  • Research Site

    Yichang, 443003

  • Research Site

    Yinchuan, 750004

  • Research Site

    Zhanjiang, 524001

  • Research Site

    Zhuzhou, 412007

Other trials in China

India14 sites

  • Research Site

    Ahmedabad, 380006

  • Research Site

    Ahmedabad, 380015

  • Research Site

    Ahmedabad, 380016

  • Research Site

    Bangalore, 560002

  • Research Site

    Bangalore, 560004

  • Research Site

    Bengaluru, 560004

  • Research Site

    Chandigarh, 160030

  • Research Site

    Chennai, 600001

  • Research Site

    Hyderabad, 500018

  • Research Site

    Kolkata, 700054

  • Research Site

    Nagpur, 440012

  • Research Site

    New Delhi, 110002

  • Research Site

    New Delhi, 110017

  • Research Site

    Vijayawada, 522002

Other trials in India

About this study

Official title: A Phase 3 Multicenter, Prospective, Randomized, Double-blind, Placebo-controlled Study to Investigate the Safety and Efficacy of ZS (Sodium Zirconium Cyclosilicate), in Patients With Hyperkalemia-HARMONIZE Asia

To evaluate the efficacy of two different doses (5 and 10 g) of ZS orally administered once daily (qd) vs placebo in maintaining normokalemia in initially hyperkalemic patients having achieved normokalemia following 24 or 48 hours of initial ZS therapy (10g TID).

Read the detailed description

This study will be conducted in approximately 35 centers in China. Before patients are randomized to the double-blind phase, they will receive open-label ZS for 24 or 48 hours during the initial phase. It is expected that approximately 490 patients will need to be enrolled, to have approximately 280 patients entered into the open-label initial phase resulting in 250 patients being randomized in the 28-day treatment study phase. Enrolment will be stopped when 250 patients have been initiated with the 28-day randomized treatment study phase.

Conditions
Hyperkalemia
Being tested
Sodium Zirconium Cyclosilicate 5g, Sodium Zirconium Cyclosilicate 10g, Placebo
Medical subject headings
Hyperkalemia

What participants receive

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

  • Sodium Zirconium Cyclosilicate 5gDrug

    Suspension administered Sodium Zirconium Cyclosilicate 5g orally once daily for 28 days after the open label initial phase with suspension administered Sodium Zirconium Cyclosilicate 10g orally three times per day for at most 2 days.

  • Sodium Zirconium Cyclosilicate 10gDrug

    Suspension administered Sodium Zirconium Cyclosilicate 10g orally once daily for 28 days after the open label initial phase with suspension administered Sodium Zirconium Cyclosilicate 10g orally three times per day for at most 2 days.

  • PlaceboDrug

    Suspension administered orally placebo once daily for 28 days after the open label initial phase with suspension administered Sodium Zirconium Cyclosilicate 10g orally three times per day for at most 2 days.

Study groups in NCT03528681
Study groupRoleWhat they receive
Sodium Zirconium Cyclosilicate 10gExperimentalSuspension administered 10g orally once daily for 28 days after the open label initial phase.
Receives: Drug: Sodium Zirconium Cyclosilicate 10g
Sodium Zirconium Cyclosilicate 5gExperimentalSuspension administered 5g orally once daily for 28 days after the open label initial phase.
Receives: Drug: Sodium Zirconium Cyclosilicate 5g
Matching PlaceboPlacebo comparatorSuspension administered orally placebo once daily for 28 days after the open label initial phase.
Receives: Drug: Placebo

What is being measured

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

  1. Least Square Mean S-K Level on Days 8-29

    Comparison between placebo and each SZC treatment group (high to low) with regard to the mean S-K level during the randomized treatment phase days 8-29. Mixed-effects models were used to estimate least-squares means.

    Measured: Days 8 to 29 (Randomized treatment study phase) used for model-based least squares mean computation

Secondary outcomes (12)

  1. Percentage of Patients Who Achieve Normokalemia

    Percentage of patients who achieve normokalemia during the open label initial phase at 24 hours and at the end of the open label phase. End of OLP is defined as Day 2 (24 hours post first dose) or Day 3 (48 hours post first dose) depending on when the subject achieved normokalemia based on the pre-dose i-STAT potassium level. The results in the table below are presented for OLP.

    Measured: Through open label initial phase

  2. Exponential Rate of Change in S-K Levels

    Exponential rate of change in S-K levels (blood) during the open-label initial phase 24 hours post-dose. Least Square Mean corresponds to the exponential rate of change i.e. the slope (for time) in terms of log-transformed S-K levels. The results in the table below are presented for OLP.

    Measured: Through 24 hours post-dose in the initial phase

  3. Absolute Change From Baseline in S-K Levels

    Absolute change from baseline in S-K levels at all measured time intervals. End of OLP is defined as Day 2 (24 hours post first dose) or Day 3 (48 hours post first dose) depending on when the subject achieved normokalemia based on the pre-dose i-STAT potassium level. The results in the table below are presented for OLP.

    Measured: Through open label initial phase

  4. Percentage Change From Baseline in S-K Levels

    Percentage change from baseline in S-K levels at all measured time intervals. End of OLP is defined as Day 2 (24 hours post first dose) or Day 3 (48 hours post first dose) depending on when the subject achieved normokalemia based on the pre-dose i-STAT potassium level. The results in the table below are presented for OLP.

    Measured: Through open label initial phase

  5. Proportion of Patients Who Remain Normokalemic During RTP

    Proportion of patients who remain normokalemic (as defined by S-K between 3.5-5.0 mmol/l, inclusive) during RTP (Day 8 to Day 29). The results in the table below are presented for RTP.

    Measured: Through 28-day randomized treatment study phase day 8-29

  6. Proportion of Normokalemic Patients at the End of RTP

    Proportion of normokalemic patients (as defined by S-K between 3.5-5.0 mmol/l, inclusive). The results in the table below are presented for RTP.

    Measured: The end of 28-day randomized treatment study phase

  7. Days Patients Remain Normokalemic

    The number of days patients remain normokalemic during days 8-29 of the randomized treatment study phase. The results in the table below are presented for RTP.

    Measured: Through days 8-29 of the randomized treatment phase.

  8. Mean Change in S-K Levels

    The mean change in S-K levels evaluated relative to the RTP baseline. The results in the table below are presented for RTP.

    Measured: Through 28-day randomized treatment phase.

  9. Mean Percent Change in S-K Levels

    The mean percent change in S-K levels evaluated relative to the RTP baseline. The results in the table below are presented for RTP.

    Measured: Through 28-day randomized treatment phase.

  10. Least Square Mean Changes in S-Aldo and P-Renin Levels

    Comparison between placebo and each SZC treatment group (high to low) with regard to the mean S-Aldo and P-Renin levels during the randomized treatment phase days 15-29.

    Measured: Through 28 day randomized treatment study phase day 15-29

  11. Hyperkalaemia at Day 29

    The number of patients with hyperkalaemia at day 29. The results in the table below are presented for RTP.

    Measured: Day 29

  12. Percentage of Patients Without Hyperkalemia

    Kaplan-Meier estimate at Day 29 of percentage of patients without hyperkalemia. The results in the table below are presented for RTP.

    Measured: Day 29 of randomized treatment phase

Timeline

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

  1. First posted18 May 2018
  2. Study start6 May 2021
  3. Primary completion15 Sep 2022
  4. Study completion15 Sep 2022

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
Double blind
Who is masked
Participant, Investigator
Enrolment
270 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03528681
Sponsor's protocol ID
D9480C00001
Acronym
HARMONIZE Asia
Status last verified
May 2025
First submitted
16 Apr 2018
Last updated
14 May 2025
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • Liang X, Lu W, Yu X, Cheng H, He Q, Peng Q, Ni Z, Long G, Wang L, Chen W, Li R, Zhao J, Zhang Y, Lisovskaja V, Tang Z. HARMONIZE Asia: A Phase III Randomized Study to Investigate the Efficacy and Safety of Sodium Zirconium Cyclosilicate in Patients with Hyperkalemia in China. Clin Ther. 2024 Sep;46(9):702-710. doi: 10.1016/j.clinthera.2024.07.004. Epub 2024 Aug 6.

    PubMed 39112102

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Sodium Zirconium Cyclosilicate 5g and Sodium Zirconium Cyclosilicate 10g in people with Hyperkalemia, run by AstraZeneca at 66 sites in 2 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 6 inclusion and 19 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 14 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 66 sites in China, India. 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 14 May 2025). 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?

Least Square Mean S-K Level on Days 8-29 (time frame: Days 8 to 29 (Randomized treatment study phase) used for model-based least squares mean computation). 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 NCT03528681, which also lists 1 linked publication.

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 14 May 2025.

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