Effects of Empagliflozin on Clinical Outcomes in Patients With Acute Decompensated Heart Failure (EMPA-RESPONSE)

University Medical Center Groningen (UMCG)

Status and phase: Completed; Phase 2

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

Treatments: Drug: Placebo Oral Tablet; Drug: Empagliflozin 10 MG

Study type: Interventional

Funder types: Other

Identifiers

NCT03200860

2017-001679-22

Details and patient eligibility

About

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.

Full 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.

Enrollment: 80 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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80 participants in 2 patient groups, including a placebo group

Empagliflozin

Active Comparator group

Description:

Empagliflozin 10 mg daily, oral, 30 days

Treatment:

Drug: Empagliflozin 10 MG

Placebo

Placebo Comparator group

Description:

Matching Placebo 10 mg daily, oral, 30 days

Treatment:

Drug: Placebo Oral Tablet