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)
Overview
- Phase
- Phase 2
- Intervention
- Empagliflozin 10 MG
- Conditions
- Heart Failure Acute
- Sponsor
- University Medical Center Groningen
- Enrollment
- 80
- Locations
- 5
- Primary Endpoint
- Diuretic Response
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
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.
Arms & Interventions
Empagliflozin
Empagliflozin 10 mg daily, oral, 30 days
Intervention: Empagliflozin 10 MG
Placebo
Matching Placebo 10 mg daily, oral, 30 days
Intervention: Placebo Oral Tablet
Outcomes
Primary Outcomes
Diuretic Response
Time Frame: Total weight change from baseline to Day 4
Weight change from baseline per 40 mg of Furosemide equivalent
Plasma NTproBNP
Time Frame: From baseline to Day 4
Change in NTproBNP
Length of Stay
Time Frame: within 60 days
Hospital stay of Index admission
Dyspnea
Time Frame: 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 Outcomes
- Inhospital Worsening Heart Failure, All Cause Mortality or Heart Failure Readmission at Day 60(60 days)
- Death and/or Heart Failure Re-admission(Day 30)
- All Cause Mortality(60 day)