HyperkalemiaPhase 2ENERGIZENCT03337477
A Study to Evaluate a Potassium Normalization Treatment Regimen Including Sodium Zirconium Cyclosilicate (ZS) Among Patients With S-K ≥5.8
A Phase 2 study testing Sodium Zirconium Cyclosilicate(ZS), Insulin and Glucose in people with Hyperkalemia, run by AstraZeneca at 25 sites in 4 countries.
Trial summary
The study is designed to determine if ZS 10g administered up to three times over 10h added to insulin and glucose in patients presenting with hyperkalemia will prove tolerable and efficacious. Patients will receive ZS or Placebo on top of standard of care treatment with insulin and glucose. 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), Insulin and Glucose
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 25 sitesin 4 countries
- Study dates
- 13 Feb 2018to 21 Dec 2018
- Phase
- Phase 2
- 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
- ≥ 18 years of age
- Potassium ≥5.8 mmol/L
Who cannot join
- Possible pseudohyperkalaemia
- Hyperkalaemia caused by any condition for which a therapy directed against the underlying cause of hyperkalaemia would be a better treatment option than treatment with insulin and glucose.
- Dialysis session expected within 4h after randomization
- Treated with any therapy intended to lower S-K between arriving at the hospital and randomization during Visit 1.
Trial locations and contacts
25 sites in 4 countries.
25 sites in 4 countries
United States12 sites
Research Site
Detroit, Michigan, 48201
Research Site
Detroit, Michigan, 48202
Research Site
Detroit, Michigan, 48235
Research Site
Durham, North Carolina, 27710
Research Site
El Paso, Texas, 79905
Research Site
Houston, Texas, 77030
Research Site
Montgomery, Alabama, 36106
Research Site
Phoenix, Arizona, 85008
Research Site
Royal Oak, Michigan, 48073
Research Site
St Louis, Missouri, 63110
Research Site
Stony Brook, New York, 11794
Research Site
Winston-Salem, North Carolina, 27157
Russia9 sites
Research Site
Kemerovo, 650002
Research Site
Kemerovo, 650066
Research Site
Moscow, 115516
Research Site
Moscow, 121374
Research Site
Perm, 614990
Research Site
Ryazan, 390039
Research Site
Saint Petersburg, 198205
Research Site
Yaroslavl, 150062
Research Site
Yekaterinburg, 620039
About this study
Official title: A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate a Potassium Normalization Treatment Regimen Including Sodium Zirconium Cyclosilicate (ENERGIZE)
The study is designed to determine if ZS 10g administered up to three times over 10h added to insulin and glucose in patients presenting with hyperkalemia will prove tolerable and efficacious. Patients will receive ZS or Placebo on top of standard of care treatment with insulin and glucose.
- Conditions
- Hyperkalemia
- Being tested
- Placebo, Sodium Zirconium Cyclosilicate(ZS), Insulin, Glucose
- 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 24h. 2 sachets administered up to three times over 10h (at 0, 4 and 10h).
Sodium Zirconium Cyclosilicate(ZS)Drug
Also called ZS, ZS-9
Suspension administered orally for a treatment period of 24h. Single dose contains 2 sachets of ZS 5g. 10g administered up to three times over 10h (at 0, 4 and 10h).
InsulinDrug
Insulin 0.1 units/kg administered as a bolus or for up to 30 minutes.
GlucoseDrug
Glucose 25g administered IV <15 minutes before the insulin.
InsulinDrug
Insulin 0.1 units/kg administered as a bolus or for up to 30 minutes.
GlucoseDrug
Glucose 25g administered IV <15 minutes before the insulin.
| Study group | Role | What they receive |
|---|---|---|
| ZS+insulin+glucose | Experimental | ZS will be administered in addition to insulin and glucose. Insulin and glucose is the current standard of care to treat serum potassium ≥5.8mmol/L. Receives: Drug: Sodium Zirconium Cyclosilicate(ZS); Drug: Insulin; Drug: Glucose |
| Placebo+insulin+glucose | Placebo comparator | Placebo will be administered in addition to insulin and glucose. Insulin and glucose is the current standard of care to treat serum potassium ≥5.8mmol/L. Receives: Drug: Placebo; Drug: Insulin; Drug: Glucose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Absolute Change in S-K From Baseline Until 4h After Start of Dosing With SZC/Placebo
The least squares means (LS-means) are derived from a linear regression model of absolute change in S-K at 4h with the following covariates: treatment group; baseline S-K; time from the start of dosing insulin to the start of dosing SZC/placebo and the dose (units/kg) of the first course of insulin. The 95% CI is associated with LS-Means.
Measured: Baseline to 4h potassium measurements.
Secondary outcomes (6)
Fraction of Patients Responding to Therapy Defined as: S-K <6.0mmol/L Between 1 and 4h and S-K <5.0mmol/L at 4h; and no Additional Potassium Lowering Therapy From 0 to 4h With Exception of the Initial Insulin Treatment
Additional therapies for hyperkalaemia are 2nd dose of insulin, Beta-agonists, Diuretics, Dialysis, Sodium bicarbonate and Potassium binders when administered with the expressed intent to lower S-K. Patients with any missing potassium value from 1h to 4h inclusive will be treated as non-responders.
Measured: Baseline to 4h potassium meansurements.
The Fraction of Patients Achieving Normokalaemia 1, 2 and 4h After Start of Dosing With SZC/Placebo
Proportion of patients achieving normokalaemia, S-K 3.5-5.0 mmol/L, at 1, 2 and 4h after start of dosing
Measured: Baseline to 4h potassium meansurements.
The Fraction of Patients Achieving S-K <5.5mmol/l 1, 2, and 4h After Start of Dosing With SZC/Placebo
Measured: Baseline to 4h potassium meansurements.
The Fraction of Patients Achieving S-K <6.0mmol/l 1, 2, and 4h After Start of Dosing With SZC/Placebo
Measured: Baseline to 4h potassium meansurements.
The Fraction of Patients Administered Additional Potassium Lowering Therapy Due to Hyperkalaemia From 0 to 4h.
Additional therapies for hyperkalaemia are 2nd dose of insulin, Beta-agonists, Diuretics, Dialysis, Sodium bicarbonate and Potassium binders when administered with the expressed intent to lower S-K.
Measured: Baseline to 4h potassium meansurements.
Mean Absolute Change in S-K From Baseline to 1h and 2h After Start of Dosing With SZC/Placebo
The least squares means (LS-means) are derived from a linear regression model of absolute change in S-K at 1h and 2h with the following covariates: treatment group; baseline S-K; time from the start of dosing insulin to the start of dosing SZC/placebo and the dose (units/kg) of the first course of insulin. The 95% CI is associated with LS-Means.
Measured: Baseline to 2h potassium measurements.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2017
- Study start13 Feb 2018
- Primary completion21 Dec 2018
- Study completion21 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HyperkalemiaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Frank Peacock, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03337477
- Sponsor's protocol ID
- D9480C00005
- Other IDs
- 2017-003955-50, 2017
- Acronym
- ENERGIZE
- Status last verified
- Jan 2020
- First submitted
- 23 Oct 2017
- Last updated
- 28 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Peacock WF, Rafique Z, Vishnevskiy K, Michelson E, Vishneva E, Zvereva T, Nahra R, Li D, Miller J. Emergency Potassium Normalization Treatment Including Sodium Zirconium Cyclosilicate: A Phase II, Randomized, Double-blind, Placebo-controlled Study (ENERGIZE). Acad Emerg Med. 2020 Jun;27(6):475-486. doi: 10.1111/acem.13954. Epub 2020 Mar 28.
PubMed 32149451
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate a Potassium Normalization Treatment Regimen Including Sodium Zirconium Cyclosilicate (ENERGIZE)
- ClinicalTrials.gov ID
- NCT03337477
- Acronym / sponsor ID
- ENERGIZE / D9480C00005
- Conditions
- Hyperkalemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 13 Feb 2018 (actual)
- Primary completion
- 21 Dec 2018 (actual)
- Study completion
- 21 Dec 2018 (actual)
- First posted
- 9 Nov 2017 (actual)
- Results
- Posted 28 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is designed to determine if ZS 10g administered up to three times over 10h added to insulin and glucose in patients presenting with hyperkalemia will prove tolerable and efficacious. Patients will receive ZS or Placebo on top of standard of care treatment with insulin and glucose.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ZS+insulin+glucose | Experimental | Drug: Sodium Zirconium Cyclosilicate(ZS), Drug: Insulin, Drug: GlucoseZS will be administered in addition to insulin and glucose. Insulin and glucose is the current standard of care to treat serum potassium ≥5.8mmol/L. |
| Placebo+insulin+glucose | Placebo comparator | Drug: Placebo, Drug: Insulin, Drug: GlucosePlacebo will be administered in addition to insulin and glucose. Insulin and glucose is the current standard of care to treat serum potassium ≥5.8mmol/L. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- ≥ 18 years of age
- Potassium ≥5.8 mmol/L
Key exclusion criteria (4 listed)
- Possible pseudohyperkalaemia
- Hyperkalaemia caused by any condition for which a therapy directed against the underlying cause of hyperkalaemia would be a better treatment option than treatment with insulin and glucose.
- Dialysis session expected within 4h after randomization
- Treated with any therapy intended to lower S-K between arriving at the hospital and randomization during Visit 1.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboSuspension administered orally for a treatment period of 24h. 2 sachets administered up to three times over 10h (at 0, 4 and 10h). | Drug | Placebo+insulin+glucose |
| Sodium Zirconium Cyclosilicate(ZS)Also: ZS, ZS-9Suspension administered orally for a treatment period of 24h. Single dose contains 2 sachets of ZS 5g. 10g administered up to three times over 10h (at 0, 4 and 10h). | Drug | ZS+insulin+glucose |
| InsulinInsulin 0.1 units/kg administered as a bolus or for up to 30 minutes. | Drug | ZS+insulin+glucose |
| GlucoseGlucose 25g administered IV <15 minutes before the insulin. | Drug | ZS+insulin+glucose |
| InsulinInsulin 0.1 units/kg administered as a bolus or for up to 30 minutes. | Drug | Placebo+insulin+glucose |
| GlucoseGlucose 25g administered IV <15 minutes before the insulin. | Drug | Placebo+insulin+glucose |
Primary outcome
Mean Absolute Change in S-K From Baseline Until 4h After Start of Dosing With SZC/Placebo
Time frame: Baseline to 4h potassium measurements.
The least squares means (LS-means) are derived from a linear regression model of absolute change in S-K at 4h with the following covariates: treatment group; baseline S-K; time from the start of dosing insulin to the start of dosing SZC/placebo and the dose (units/kg) of the first course of insulin. The 95% CI is associated with LS-Means.
6 secondary outcomes
Fraction of Patients Responding to Therapy Defined as: S-K <6.0mmol/L Between 1 and 4h and S-K <5.0mmol/L at 4h; and no Additional Potassium Lowering Therapy From 0 to 4h With Exception of the Initial Insulin Treatment
Time frame: Baseline to 4h potassium meansurements.
The Fraction of Patients Achieving Normokalaemia 1, 2 and 4h After Start of Dosing With SZC/Placebo
Time frame: Baseline to 4h potassium meansurements.
The Fraction of Patients Achieving S-K <5.5mmol/l 1, 2, and 4h After Start of Dosing With SZC/Placebo
Time frame: Baseline to 4h potassium meansurements.
The Fraction of Patients Achieving S-K <6.0mmol/l 1, 2, and 4h After Start of Dosing With SZC/Placebo
Time frame: Baseline to 4h potassium meansurements.
The Fraction of Patients Administered Additional Potassium Lowering Therapy Due to Hyperkalaemia From 0 to 4h.
Time frame: Baseline to 4h potassium meansurements.
Mean Absolute Change in S-K From Baseline to 1h and 2h After Start of Dosing With SZC/Placebo
Time frame: Baseline to 2h potassium measurements.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32149451Peacock WF, Rafique Z, Vishnevskiy K, Michelson E, Vishneva E, Zvereva T, Nahra R, Li D, Miller J. Emergency Potassium Normalization Treatment Including Sodium Zirconium Cyclosilicate: A Phase II, Randomized, Double-blind, Placebo-controlled Study (ENERGIZE). Acad Emerg Med. 2020 Jun;27(6):475-486. doi: 10.1111/acem.13954. Epub 2020 Mar 28.
- CSP\_redacted\_versionLink provided by the sponsor.
- SAP\_redacted\_versionLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frank Peacock, MD principal investigator
Baylor College of Medicine
25 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sodium Zirconium Cyclosilicate(ZS), Insulin and Glucose in people with Hyperkalemia, run by AstraZeneca at 25 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 2 inclusion and 4 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 28 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States, Russia, Denmark, Italy. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 28 Jan 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?
Mean Absolute Change in S-K From Baseline Until 4h After Start of Dosing With SZC/Placebo (time frame: Baseline to 4h potassium measurements.). 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 NCT03337477, 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 28 Jan 2020.