Effects of Empagliflozin on Clinical Outcomes in Patients With Acute Decompensated Heart Failure

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Randomized, Double Blind, Placebo Controlled, Multicenter Pilot Study on the Effects of Empagliflozin on Clinical Outcomes in Patients With Acute Decompensated Heart Failure (EMPA-RESPONSE-AHF)

Conditions
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Heart Failure Acute, Heart Failure，Congestive, Heart Failure; With Decompensation

Intervention / Treatment
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* Drug: Empagliflozin 10 MG
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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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: Dyspnea at rest or with minimal exertion Signs of congestion, such as edema, rales, and/or congestion on chest radiograph BNP ≥350 pg/mL or NT-proBNP ≥1,400 pg/mL (for patients with AF: BNP≥500 pg/mL or NT-proBNP ≥2,000 pg/mL) Treated with loop diuretics at 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: Diabetes Mellitus Type I Dyspnea primarily due to non-cardiac causes Cardiogenic shock Acute coronary syndrome within 30 days prior to randomization Planned or recent percutaneous or surgical coronary intervention within 30 days prior to randomization Signs of keto-acidosis and/or hyperosmolar hyperglaecemic syndrome (pH>7.30 and glucose >15 mmol/L and HCO3>18 mmol/L) Pregnant or nursing (lactating) women Current participation in any interventional study Inability to follow instructions or comply with follow-up procedures Any other medical conditions that may put the patient at risk or influence study results in the investigator's opinion, or that the investigator deems unsuitable for the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized, placebo-controlled, double-blind, parallel group, multicenter study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Empagliflozin<br>Empagliflozin 10 mg daily, oral, 30 days | Drug: Empagliflozin 10 MG<br>* 10 mg daily, oral, 30 days<br>|
| Placebo Comparator: Placebo<br>Matching Placebo 10 mg daily, oral, 30 days | Drug: Placebo Oral Tablet<br>* Matching Placebo, 10 mg daily, oral, 30 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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heart failure, diuretic response, empagliflozin