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Acute decompensated heart failure is the fastest growing disease in the world and the leading cause of hospital admissions worldwide. Short term mortality and rehospitalization are extremely high (20-30% within 3-6 months) and there is no therapy available that improves clinical outcome in these patients. Empagliflozin is a selective inhibitor of sodium glucose co-transporter with diuretic and renal- protective properties. In patients with type 2 diabetes at high risk for cardiovascular events, empagliflozin reduced the risk of hospitalization for heart failure by 35%. Based on the promising pharmacological profile of empagliflozin in relation to the needs for treatment of acute decompensated heart failure, we hypothesize that empagliflozin exerts positive effects in acute decompensated heart failure, with or without diabetes,
This is a randomized, placebo-controlled, double-blind, parallel group, multicenter study in subjects admitted for acute decompensated heart failure. Eighty eligible subjects will be randomized in a 1:1 ratio to receive either empagliflozin 10 mg/day or matched placebo.
This is a randomized, placebo-controlled, double-blind, parallel group, multicenter study in subjects admitted for acute decompensated heart failure. Eighty eligible subjects will be randomized in a 1:1 ratio to receive either empagliflozin 10 mg/day or matched placebo.
Treatment will be continued until 30 days after index event, and primary efficacy measurements will be carried out during hospitalization and safety events until 60 days after index hospitalisation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Empagliflozin | Active Comparator | Empagliflozin 10 mg daily, oral, 30 days |
|
| Placebo | Placebo Comparator | Matching Placebo 10 mg daily, oral, 30 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Empagliflozin 10 MG | Drug | 10 mg daily, oral, 30 days |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Dyspnea | Change in Dyspnea on VAS analogue scale (AUC) VAS Score is a measure/scale where patients on a scale from 0 to 100 can assign their current dyspnea score. 0 means there can be no worse dyspnea, 100 means it cannot get any better (perfect). The change in Dyspnea VAS means higher score is better outcomes. Individual changes in VAS score are be visualized (virtually) as a curve where the X-axis shows study day baseline to day 4, and y-axis shows VAS score. Using this approach, area under the curves for each study day (trapezoids) can be calculated, and added together, resulting in an overall VAS AUC score (mmxh) and change in VAS can be caculated | From baseline to Day 4 |
| Diuretic Response | Weight change from baseline per 40 mg of Furosemide equivalent | Total weight change from baseline to Day 4 |
| Length of Stay | Hospital stay of Index admission | within 60 days |
| Plasma NTproBNP | Change in NTproBNP | From baseline to Day 4 |
| Measure | Description | Time Frame |
|---|---|---|
| Death and/or Heart Failure Re-admission | Death and/or heart failure re-admission at day 30 | Day 30 |
| Inhospital Worsening Heart Failure, All Cause Mortality or Heart Failure Readmission at Day 60 |
| Measure | Description | Time Frame |
|---|---|---|
| Serious Adverse Events | SAE including all cause mortality. Per request Clintrials.gov different from Protocol definition | 60 days |
Inclusion Criteria:
Male or female >18 years of age; Women of non-child-bearing potential must have a documentation of surgical sterilization (hysterectomy and/or bilateral oophorectomy) OR must have experienced menopause (no menses for >12 months). Women of child bearing potential must have a negative pregnancy test, AND must use highly effective methods of contraception during treatment with IP plus 5 days after the end of study drug administration.
Hospitalized for AHF; AHF is defined as including all of the followings measured at any time between presentation (including the emergency department) and the end of screening:
Able to be randomized within 24 hours from presentation to the hospital
Able and willing to provide freely given written informed consent
eGFR (CKD-EPI) ≥30 ml/min/1.73m2 between presentation and randomization
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Adriaan Voors, Prof. Dr. | University Medical Center Groningen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| TREANT Zorggroep | Emmen | Drenthe | Netherlands | |||
| Jeroen Bosch Ziekenhuis |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26378978 | Background | Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015 Nov 26;373(22):2117-28. doi: 10.1056/NEJMoa1504720. Epub 2015 Sep 17. | |
| 27299675 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Empagliflozin | Empagliflozin 10 mg daily, oral, 30 days Empagliflozin 10 MG: 10 mg daily, oral, 30 days |
| FG001 | Placebo | Matching Placebo 10 mg daily, oral, 30 days Placebo Oral Tablet: Matching Placebo, 10 mg daily, oral, 30 days |
| 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 | Oct 20, 2017 | Feb 9, 2020 |
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randomized, placebo-controlled, double-blind, parallel group, multicenter study
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double blind, placebo controlled
| Placebo Oral Tablet |
| Drug |
Matching Placebo, 10 mg daily, oral, 30 days |
|
Inhospital Worsening Heart Failure or All Cause mortality or Heart Failure Readmission at day 60
| 60 days |
| All Cause Mortality | All Cause Mortality at 60 days | 60 day |
| 's-Hertogenbosch |
| North Brabant |
| Netherlands |
| ISALA Klinieken | Zwolle | Overijssel | Netherlands |
| Antonius Ziekenhuis | Sneek | Provincie Friesland | Netherlands |
| University Medical Center Groningen | Groningen | 9700RB | Netherlands |
| Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, Johansen OE, Woerle HJ, Broedl UC, Zinman B; EMPA-REG OUTCOME Investigators. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016 Jul 28;375(4):323-34. doi: 10.1056/NEJMoa1515920. Epub 2016 Jun 14. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Empagliflozin | Empagliflozin 10 mg daily, oral, 30 days Empagliflozin 10 MG: 10 mg daily, oral, 30 days |
| BG001 | Placebo | Matching Placebo 10 mg daily, oral, 30 days Placebo Oral Tablet: Matching Placebo, 10 mg daily, oral, 30 days |
| 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, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Age, Continuous | Median | Inter-Quartile Range | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||||
| NTproBNP | Median | Inter-Quartile Range | pg/mL |
|
| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Dyspnea | Change in Dyspnea on VAS analogue scale (AUC) VAS Score is a measure/scale where patients on a scale from 0 to 100 can assign their current dyspnea score. 0 means there can be no worse dyspnea, 100 means it cannot get any better (perfect). The change in Dyspnea VAS means higher score is better outcomes. Individual changes in VAS score are be visualized (virtually) as a curve where the X-axis shows study day baseline to day 4, and y-axis shows VAS score. Using this approach, area under the curves for each study day (trapezoids) can be calculated, and added together, resulting in an overall VAS AUC score (mmxh) and change in VAS can be caculated | Posted | Mean | Standard Deviation | mmxh | From baseline to Day 4 |
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| Primary | Diuretic Response | Weight change from baseline per 40 mg of Furosemide equivalent | Posted | Mean | Standard Deviation | kg/40 mg Furosemide equivalent at day 4 | Total weight change from baseline to Day 4 |
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| Primary | Length of Stay | Hospital stay of Index admission | Posted | Median | Inter-Quartile Range | days | within 60 days |
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| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Plasma NTproBNP | Change in NTproBNP | Posted | Mean | Standard Deviation | % change in NTproBNP at day 4 | From baseline to Day 4 |
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| Secondary | Death and/or Heart Failure Re-admission | Death and/or heart failure re-admission at day 30 | Posted | Count of Participants | Participants | Day 30 |
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| Secondary | Inhospital Worsening Heart Failure, All Cause Mortality or Heart Failure Readmission at Day 60 | Inhospital Worsening Heart Failure or All Cause mortality or Heart Failure Readmission at day 60 | Posted | Count of Participants | Participants | 60 days |
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| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | All Cause Mortality | All Cause Mortality at 60 days | Posted | Count of Participants | Participants | 60 day |
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| Other Pre-specified | Serious Adverse Events | SAE including all cause mortality. Per request Clintrials.gov different from Protocol definition | Posted | Count of Participants | Participants | 60 days |
|
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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 | Empagliflozin | Empagliflozin 10 mg daily, oral, 30 days Empagliflozin 10 MG: 10 mg daily, oral, 30 days | 1 | 40 | 8 | 40 | 29 | 40 |
| EG001 | Placebo | Matching Placebo 10 mg daily, oral, 30 days Placebo Oral Tablet: Matching Placebo, 10 mg daily, oral, 30 days | 3 | 39 | 10 | 39 | 31 | 39 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Worsening Heart Failure | Cardiac disorders | Systematic Assessment |
| ||
| Worsening Renal Function | General disorders | Systematic Assessment |
| ||
| Acute Kidney Injury | General disorders | Systematic Assessment |
| ||
| Angioedema | Injury, poisoning and procedural complications | Non-systematic Assessment |
| ||
| Hypovolemic shock | Cardiac disorders | Non-systematic Assessment |
| ||
| Delirium | General disorders | Non-systematic Assessment |
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| Heart Failure | Cardiac disorders | Systematic Assessment |
| ||
| Atrial Fibrillation | Cardiac disorders | Systematic Assessment |
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| S. Aureus Bacteremia | Infections and infestations | Non-systematic Assessment |
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| Syncope | Cardiac disorders | Non-systematic Assessment |
| ||
| Respiratory Failure | General disorders | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiovascular | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Respiratory | General disorders | Non-systematic Assessment |
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| Gastrointestinal | Gastrointestinal disorders | Non-systematic Assessment |
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| Renal/Urinary | General disorders | Systematic Assessment |
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| Metabolic | Metabolism and nutrition disorders | Systematic Assessment |
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| Musculoskeletal | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Other | General disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Prof. dr. A.A. Voors | University Medical Center Groningen - Department of Cardiology | 0031503616161 | a.a.voors@umcg.nl |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 3, 2019 | Feb 9, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| C570240 | empagliflozin |
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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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