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

Phase 2

Completed

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

Brief Summary: 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: 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.

Recruitment & Eligibility

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:
1. Dyspnea at rest or with minimal exertion
2. Signs of congestion, such as edema, rales, and/or congestion on chest radiograph
3. 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)
4. 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.

Arm && Interventions

Group	Intervention	Description
Empagliflozin	Empagliflozin 10 MG	Empagliflozin 10 mg daily, oral, 30 days
Placebo	Placebo Oral Tablet	Matching Placebo 10 mg daily, oral, 30 days

Primary Outcome Measures

Name	Time	Method
Length of Stay	within 60 days	Hospital stay of Index admission
Diuretic Response	Total weight change from baseline to Day 4	Weight change from baseline per 40 mg of Furosemide equivalent
Plasma NTproBNP	From baseline to Day 4	Change in NTproBNP
Dyspnea	From baseline to Day 4	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

Secondary Outcome Measures

Name	Time	Method
Inhospital Worsening Heart Failure, All Cause Mortality or Heart Failure Readmission at Day 60	60 days	Inhospital Worsening Heart Failure or All Cause mortality or Heart Failure Readmission at day 60
Death and/or Heart Failure Re-admission	Day 30	Death and/or heart failure re-admission at day 30
All Cause Mortality	60 day	All Cause Mortality at 60 days

Locations (5): Jeroen Bosch Ziekenhuis
🇳🇱
Den Bosch, Brabant, Netherlands
TREANT Zorggroep
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Emmen, Drenthe, Netherlands
ISALA Klinieken
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Zwolle, Overijssel, Netherlands
Antonius Ziekenhuis
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Sneek, Friesland, Netherlands
University Medical Center Groningen
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Groningen, Netherlands