Back to resultsA Study to Evaluate a Potassium Normalization Treatment Regimen Including Sodium Zirconium Cyclosilicate (ZS) Among Patients With S-K ≥5.8 (ENERGIZE)
Primary Purpose
Hyperkalemia
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo
Sodium Zirconium Cyclosilicate(ZS)
Insulin
Glucose
Insulin
Glucose
Sponsored by
About this trial
This is an interventional treatment trial for Hyperkalemia
Eligibility Criteria
Inclusion Criteria:
≥ 18 years of age
Potassium ≥5.8 mmol/L
Exclusion Criteria:
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.
Sites / Locations
- Research Site
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Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
ZS+insulin+glucose
Placebo+insulin+glucose
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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
The Fraction of Patients Achieving S-K <5.5mmol/l 1, 2, and 4h After Start of Dosing With SZC/Placebo
The Fraction of Patients Achieving S-K <6.0mmol/l 1, 2, and 4h After Start of Dosing With SZC/Placebo
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03337477
Brief Title
A Study to Evaluate a Potassium Normalization Treatment Regimen Including Sodium Zirconium Cyclosilicate (ZS) Among Patients With S-K ≥5.8
Acronym
ENERGIZE
Official Title
A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate a Potassium Normalization Treatment Regimen Including Sodium Zirconium Cyclosilicate (ENERGIZE)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
February 13, 2018 (Actual)
Primary Completion Date
December 21, 2018 (Actual)
Study Completion Date
December 21, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperkalemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
70 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ZS+insulin+glucose
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo+insulin+glucose
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Suspension administered orally for a treatment period of 24h. 2 sachets administered up to three times over 10h (at 0, 4 and 10h).
Intervention Type
Drug
Intervention Name(s)
Sodium Zirconium Cyclosilicate(ZS)
Other Intervention Name(s)
ZS, ZS-9
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Insulin
Intervention Description
Insulin 0.1 units/kg administered as a bolus or for up to 30 minutes.
Intervention Type
Drug
Intervention Name(s)
Glucose
Intervention Description
Glucose 25g administered IV <15 minutes before the insulin.
Intervention Type
Drug
Intervention Name(s)
Insulin
Intervention Description
Insulin 0.1 units/kg administered as a bolus or for up to 30 minutes.
Intervention Type
Drug
Intervention Name(s)
Glucose
Intervention Description
Glucose 25g administered IV <15 minutes before the insulin.
Primary Outcome Measure Information:
Title
Mean Absolute Change in S-K From Baseline Until 4h After Start of Dosing With SZC/Placebo
Description
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.
Time Frame
Baseline to 4h potassium measurements.
Secondary Outcome Measure Information:
Title
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
Description
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.
Time Frame
Baseline to 4h potassium meansurements.
Title
The Fraction of Patients Achieving Normokalaemia 1, 2 and 4h After Start of Dosing With SZC/Placebo
Description
Proportion of patients achieving normokalaemia, S-K 3.5-5.0 mmol/L, at 1, 2 and 4h after start of dosing
Time Frame
Baseline to 4h potassium meansurements.
Title
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.
Title
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.
Title
The Fraction of Patients Administered Additional Potassium Lowering Therapy Due to Hyperkalaemia From 0 to 4h.
Description
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.
Time Frame
Baseline to 4h potassium meansurements.
Title
Mean Absolute Change in S-K From Baseline to 1h and 2h After Start of Dosing With SZC/Placebo
Description
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.
Time Frame
Baseline to 2h potassium measurements.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
130 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
≥ 18 years of age
Potassium ≥5.8 mmol/L
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frank Peacock, MD
Organizational Affiliation
Baylor College of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Montgomery
State/Province
Alabama
ZIP/Postal Code
36106
Country
United States
Facility Name
Research Site
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85008
Country
United States
Facility Name
Research Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Research Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Research Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48235
Country
United States
Facility Name
Research Site
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States
Facility Name
Research Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Research Site
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794
Country
United States
Facility Name
Research Site
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Research Site
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Research Site
City
El Paso
State/Province
Texas
ZIP/Postal Code
79905
Country
United States
Facility Name
Research Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Research Site
City
Esbjerg
ZIP/Postal Code
6700
Country
Denmark
Facility Name
Research Site
City
Herning
ZIP/Postal Code
7400
Country
Denmark
Facility Name
Research Site
City
Novara
ZIP/Postal Code
28100
Country
Italy
Facility Name
Research Site
City
Piombino
ZIP/Postal Code
57025
Country
Italy
Facility Name
Research Site
City
Kemerovo
ZIP/Postal Code
650002
Country
Russian Federation
Facility Name
Research Site
City
Kemerovo
ZIP/Postal Code
650066
Country
Russian Federation
Facility Name
Research Site
City
Moscow
ZIP/Postal Code
115516
Country
Russian Federation
Facility Name
Research Site
City
Moscow
ZIP/Postal Code
121374
Country
Russian Federation
Facility Name
Research Site
City
Perm
ZIP/Postal Code
614990
Country
Russian Federation
Facility Name
Research Site
City
Ryazan
ZIP/Postal Code
390039
Country
Russian Federation
Facility Name
Research Site
City
Saint-Petersburg
ZIP/Postal Code
198205
Country
Russian Federation
Facility Name
Research Site
City
Yaroslavl
ZIP/Postal Code
150062
Country
Russian Federation
Facility Name
Research Site
City
Yekaterinburg
ZIP/Postal Code
620039
Country
Russian Federation
12. IPD Sharing Statement
Citations:
PubMed Identifier
32149451
Citation
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.
Results Reference
derived
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A Study to Evaluate a Potassium Normalization Treatment Regimen Including Sodium Zirconium Cyclosilicate (ZS) Among Patients With S-K ≥5.8
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