A Study to Evaluate a Potassium Normalization Treatment Regimen Including Sodium Zirconium Cyclosilicate (ZS) Among Patients With S-K ≥5.8 (ENERGIZE)

• ClinicalTrials.gov Identifier: NCT03337477
• Recruitment Status: Completed
• First Posted: November 9, 2017
• Results First Posted: January 28, 2020
• Last Update Posted: January 28, 2020
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

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.

Condition or disease	Intervention/treatment	Phase
Hyperkalemia	Drug: Placebo; Drug: Sodium Zirconium Cyclosilicate(ZS); Drug: Insulin; Drug: Glucose	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate a Potassium Normalization Treatment Regimen Including Sodium Zirconium Cyclosilicate (ENERGIZE)
• Actual Study Start Date: February 13, 2018
• Actual Primary Completion Date: December 21, 2018
• Actual Study Completion Date: December 21, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: ZS+insulin+glucose; 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.	Drug: Sodium Zirconium Cyclosilicate(ZS); 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).; Other Name: ZS, ZS-9; Drug: Insulin; Insulin 0.1 units/kg administered as a bolus or for up to 30 minutes.; Drug: Glucose; Glucose 25g administered IV <15 minutes before the insulin.
Placebo Comparator: Placebo+insulin+glucose; 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.	Drug: Placebo; Suspension administered orally for a treatment period of 24h. 2 sachets administered up to three times over 10h (at 0, 4 and 10h).; Drug: Insulin; Insulin 0.1 units/kg administered as a bolus or for up to 30 minutes.; Drug: Glucose; Glucose 25g administered IV <15 minutes before the insulin.

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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. ]
   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.
2. The Fraction of Patients Achieving Normokalaemia 1, 2 and 4h After Start of Dosing With SZC/Placebo [ Time Frame: Baseline to 4h potassium meansurements. ]
   Proportion of patients achieving normokalaemia, S-K 3.5-5.0 mmol/L, at 1, 2 and 4h after start of dosing
3. 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. ]
4. 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. ]
5. The Fraction of Patients Administered Additional Potassium Lowering Therapy Due to Hyperkalaemia From 0 to 4h. [ Time Frame: Baseline to 4h potassium meansurements. ]
   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.
6. 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. ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 130 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Alabama

Research Site

Montgomery, Alabama, United States, 36106

United States, Arizona

Research Site

Phoenix, Arizona, United States, 85008

United States, Michigan

Research Site

Detroit, Michigan, United States, 48201

Research Site

Detroit, Michigan, United States, 48202

Research Site

Detroit, Michigan, United States, 48235

Research Site

Royal Oak, Michigan, United States, 48073

United States, Missouri

Research Site

Saint Louis, Missouri, United States, 63110

United States, New York

Research Site

Stony Brook, New York, United States, 11794

United States, North Carolina

Research Site

Durham, North Carolina, United States, 27710

Research Site

Winston-Salem, North Carolina, United States, 27157

United States, Texas

Research Site

El Paso, Texas, United States, 79905

Research Site

Houston, Texas, United States, 77030

Denmark

Research Site

Esbjerg, Denmark, 6700

Research Site

Herning, Denmark, 7400

Italy

Research Site

Novara, Italy, 28100

Research Site

Piombino, Italy, 57025

Russian Federation

Research Site

Kemerovo, Russian Federation, 650002

Research Site

Kemerovo, Russian Federation, 650066

Research Site

Moscow, Russian Federation, 115516

Research Site

Moscow, Russian Federation, 121374

Research Site

Perm, Russian Federation, 614990

Research Site

Ryazan, Russian Federation, 390039

Research Site

Saint-Petersburg, Russian Federation, 198205

Research Site

Yaroslavl, Russian Federation, 150062

Research Site

Yekaterinburg, Russian Federation, 620039

Sponsors and Collaborators

AstraZeneca

Investigators

• Principal Investigator: Frank Peacock, MD; Baylor College of Medicine

  Study Documents (Full-Text)

Documents provided by AstraZeneca:

Study Protocol  [PDF] June 13, 2018

Statistical Analysis Plan  [PDF] November 9, 2018

More Information

Additional Information:

CSP_redacted_version 

SAP_redacted_version 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT03337477
• Other Study ID Numbers: D9480C00005; 2017-003955-50 ( EudraCT Number )
• First Posted: November 9, 2017
• Results First Posted: January 28, 2020
• Last Update Posted: January 28, 2020
• Last Verified: January 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hyperkalemia; Water-Electrolyte Imbalance; Metabolic Diseases; Insulin; Insulin, Globin Zinc; Hypoglycemic Agents; Physiological Effects of Drugs