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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-003955-50 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Suspension administered orally for a treatment period of 24h. 2 sachets administered up to three times over 10h (at 0, 4 and 10h). |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline to 4h potassium measurements. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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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.
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| Name | Affiliation | Role |
|---|---|---|
| Frank Peacock, MD | Baylor College of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Montgomery | Alabama | 36106 | United States | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32149451 | Derived | 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. |
| Label | URL |
|---|---|
| CSP\_redacted\_version | View source |
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Patients with S-K ≥5.8 mmol/L for whom treatment with insulin and glucose to manage hyperkalaemia has been determined medically appropriate by the Investigator. The study originally recruited patients with S-K ≥6.0 mmol/L; however, this inclusion criterion was updated during CSP Amendment to allow enrolment of patients with S-K ≥5.8 mmol/L.
Participants took part in the study in the United States, Russia, Denmark and Italy from 13 February 2018 to 21 December 2018.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sodium Zirconium Cyclosilicate (SZC) 10g | SZC will be administered in addition to insulin and glucose. |
| FG001 | Placebo | Placebo will be administered in addition to insulin and glucose. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 13, 2018 | Dec 11, 2019 |
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| Sodium Zirconium Cyclosilicate(ZS) | Drug | 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). |
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| Insulin | Drug | Insulin 0.1 units/kg administered as a bolus or for up to 30 minutes. |
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| Glucose | Drug | Glucose 25g administered IV <15 minutes before the insulin. |
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| Insulin | Drug | Insulin 0.1 units/kg administered as a bolus or for up to 30 minutes. |
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| Glucose | Drug | Glucose 25g administered IV <15 minutes before the insulin. |
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| 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 | 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 | 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 | 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. | 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. | Baseline to 2h potassium measurements. |
| Phoenix |
| Arizona |
| 85008 |
| United States |
| Research Site | Detroit | Michigan | 48201 | United States |
| Research Site | Detroit | Michigan | 48202 | United States |
| Research Site | Detroit | Michigan | 48235 | United States |
| Research Site | Royal Oak | Michigan | 48073 | United States |
| Research Site | St Louis | Missouri | 63110 | United States |
| Research Site | Stony Brook | New York | 11794 | United States |
| Research Site | Durham | North Carolina | 27710 | United States |
| Research Site | Winston-Salem | North Carolina | 27157 | United States |
| Research Site | El Paso | Texas | 79905 | United States |
| Research Site | Houston | Texas | 77030 | United States |
| Research Site | Esbjerg | 6700 | Denmark |
| Research Site | Herning | 7400 | Denmark |
| Research Site | Novara | 28100 | Italy |
| Research Site | Piombino | 57025 | Italy |
| Research Site | Kemerovo | 650002 | Russia |
| Research Site | Kemerovo | 650066 | Russia |
| Research Site | Moscow | 115516 | Russia |
| Research Site | Moscow | 121374 | Russia |
| Research Site | Perm | 614990 | Russia |
| Research Site | Ryazan | 390039 | Russia |
| Research Site | Saint Petersburg | 198205 | Russia |
| Research Site | Yaroslavl | 150062 | Russia |
| Research Site | Yekaterinburg | 620039 | Russia |
| SAP\_redacted\_version | View source |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Sodium Zirconium Cyclosilicate (SZC) 10g | SZC will be administered in addition to insulin and glucose. |
| BG001 | Placebo | Placebo will be administered in addition to insulin and glucose. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Country | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Secondary | 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. | Full analysis set: all randomized patients. However, patients with no baseline or/and post-baseline data (one patient in each group) were excluded from the analysis. | Posted | Number | Proportion of participants | Baseline to 4h potassium meansurements. |
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| Secondary | 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 | Full analysis set: all randomized patients. However, patients with no baseline or/and post-baseline data (one patient in each group) were excluded from the analysis. | Posted | Number | Proportion of participants | Baseline to 4h potassium meansurements. |
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| ||||||||||||||||||||||||||||||
| Secondary | The Fraction of Patients Achieving S-K <5.5mmol/l 1, 2, and 4h After Start of Dosing With SZC/Placebo | Full analysis set: all randomized patients. However, patients with no baseline or/and post-baseline data (one patient in each group) were excluded from the analysis. | Posted | Number | Proportion of paticipants | Baseline to 4h potassium meansurements. |
|
| |||||||||||||||||||||||||||||||
| Secondary | The Fraction of Patients Achieving S-K <6.0mmol/l 1, 2, and 4h After Start of Dosing With SZC/Placebo | Full analysis set: all randomized patients. However, patients with no baseline or/and post-baseline data (one patient in each group) were excluded from the analysis. | Posted | Number | Proportion of paticipants | Baseline to 4h potassium meansurements. |
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| Secondary | 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. | Full analysis set: all randomized patients. However, patients with no baseline or/and post-baseline data (one patient in each group) were excluded from the analysis. | Posted | Number | Proportion of participants | Baseline to 4h potassium meansurements. |
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| Secondary | 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 analysis set: all randomized patients. However, patients with no baseline or/and post-baseline data (one patient in each group) were excluded from the analysis. | Posted | Least Squares Mean | 95% Confidence Interval | mmol/L | Baseline to 2h potassium measurements. |
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| Primary | 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. | Full analysis set: all randomized patients. However, patients with no baseline or/and post-baseline data (one patient in each group) were excluded from the analysis. | Posted | Least Squares Mean | 95% Confidence Interval | mmol/L | Baseline to 4h potassium measurements. |
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AEs, including SAEs, were collected from time of signature of informed consent form throughout the treatment period and including the follow-up period (visit 2 or last contact). AE/SAEs occurring between 0h to 24h and AE/SAEs occurring after 24h (time calculated from the start of the administration of insulin) were analysed separately.
Patients at risk are the ones who got at least one dose, namely 29 in SZC and 33 in placebo.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sodium Zirconium Cyclosilicate (SZC) 10g (0-24h) | SZC will be administered in addition to insulin and glucose. AEs collected between 0-24h. | 0 | 29 | 1 | 29 | 4 | 29 |
| EG001 | Placebo (0-24h) | Placebo will be administered in addition to insulin and glucose. AEs collected between 0-24h. | 1 | 33 | 2 | 33 | 5 | 33 |
| EG002 | Sodium Zirconium Cyclosilicate (SZC) 10g (After 24h) | SZC will be administered in addition to insulin and glucose. AEs collected after 24h. | 0 | 29 | 2 | 29 | 3 | 29 |
| EG003 | Placebo (After 24 h) | Placebo will be administered in addition to insulin and glucose. AEs collected after 24h. | 0 | 33 | 3 | 33 | 0 | 33 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypotension | Vascular disorders | MedDRA version 21.1 | Systematic Assessment |
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| Clonic convulsion | Nervous system disorders | MedDRA version 21.1 | Systematic Assessment |
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| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA version 21.1 | Systematic Assessment |
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| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA version 21.1 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA version 21.1 | Systematic Assessment |
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| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA version 21.1 | Systematic Assessment |
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| Cardiac failure | Cardiac disorders | MedDRA version 21.1 | Systematic Assessment |
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| Tibia fracture | Injury, poisoning and procedural complications | MedDRA version 21.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA version 21.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA version 21.1 | Systematic Assessment |
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| Procedural pain | Injury, poisoning and procedural complications | MedDRA version 21.1 | Systematic Assessment |
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Recruitment was stopped at 70 patients randomized instead of 132, as initially planned.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Information Center | AstraZeneca Clinical | +1 877 240 9479 | information.center@astrazeneca.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 9, 2018 | Dec 11, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| D006947 | Hyperkalemia |
| ID | Term |
|---|---|
| D014883 | Water-Electrolyte Imbalance |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C000597310 | sodium zirconium cyclosilicate |
| D007328 | Insulin |
| D005947 | Glucose |
| ID | Term |
|---|---|
| D011384 | Proinsulin |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D006601 | Hexoses |
| D009005 | Monosaccharides |
| D000073893 | Sugars |
| D002241 | Carbohydrates |
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| >=50 - <65 years |
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| >=65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Italy |
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| Russia |
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| United States |
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