EMPA Acute Heart Failure

RWTH Aachen University

Status and phase: Terminated; Phase 2

Conditions: Acute Heart Failure; Diabetes Mellitus, Type 2

Treatments: Drug: Placebo; Drug: Empagliflozin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03554200

2017-002695-45 (EudraCT Number)

15-156

Details and patient eligibility

About

In this study the investigators are aiming to treat patients with acute heart failure with or without diabetes with Empagliflozin or placebo. Given the beneficial effects of Empagliflozin on heart failure hospitalization in the EMPA-REG OUTCOME trial, the investigators do expect a similar beneficial effect to be present in patients with acute heart failure. Acute heart failure is a state of hydropic decompensation resulting in dyspnea and congestions, caused by different etiologies of cardiac disease. Recompensation is reached by application of diuretic drugs and fluid restriction.

Full description

In the present study patients will be randomized into 2 groups (standard of care + Empagliflozin 10 mg/d or standard of care + placebo). Cardiac output will be assessed by a medical device for noninvasive monitoring of hemodynamic parameters (cardiac output, systemic vascular resistance, stroke volume and blood pressure) using finger cuff technology for pulse contour analysis.

These investigations will inform about Empagliflozin dependent effects on hemodynamic and cardiac function in patients with acute heart failure. The investigation will further assess the therapeutic efficacy of Empagliflozin on heart failure symptoms using objective (respiratory rate, oxygen requirement, peak expiratory flow rate, urinary volume, body weight, diuretic requirement, length of hospital stay) and well accepted, patient orientated secondary endpoints. In addition, metabolic regulators and parameters relevant for cardiac function and substrate metabolism will be assessed to further investigate possible mechanisms of Empagliflozin-dependent actions on cardiac function.

Enrollment: 19 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥ 18 years
2. Patients with acute heart failure with associated signs or symptoms (dyspnea on exertion, orthopnea, paroxysmal dyspnea, peripheral oedema, chest x-ray with pulmonary congestion)
3. Serum levels of NT-proBNP ≥ 1000 pg/ml within 48 hours of Informed Consent
4. Written informed consent prior to study participation

Exclusion criteria

1. Type 1 diabetes
2. Participants of child-bearing age without adequate contraception
3. Pregnancy or lactating females
4. Cardiogenic shock
5. Acute coronary syndrome within 30 days prior to randomization
6. Planned or recent percutaneous or surgical coronary intervention within 30 days prior to randomization
7. Signs of ketoacidosis and/or hyperosmolar hyperglycemic syndrome (pH ≤ 7.30 and glucose >14 mmol/l and HCO3- ≤ 18 mmol/l)
8. Signs of uncontrolled active infection
9. Dyspnea due to non-cardiac causes (severe pulmonary disease, anemia, severe obesity), non-HF causes such as acute or chronic respiratory disorders
10. Coronary artery disease with requirement for revascularization within the study period
11. Renal impairment (GFR < 20 ml/min/1,73 m2)
12. Known hepatic impairment (as evidenced by total bilirubin >3 mg/dL) or history of cirrhosis with evidence of portal hypertension (e.g., presence of esophageal varices)
13. Uncontrolled thyroid disease
14. Endocrinopathies like Graves' disease, acromegaly, Cushings' disease
15. Hypertensive retinopathy or encephalopathy
16. Bariatric surgery in last 2 years prior to randomization
17. Patients in whom study participation is not deemed appropriate under consideration of clinical wellbeing by the principal investigator
18. The subject is mentally or legally incapacitated
19. The subject received an investigational drug within 30 days prior to inclusion into this study
20. Urinary tract infections or significant formation of residual urine in medical history
21. Patients with particular risk for ketoacidosis (alcohol abuse, pancreatitis, pancreatic insulin deficiency from any cause, caloric restriction etc.) or ketoacidosis in the past
22. Frequent hypoglycaemic events (in the opinion of the investigator)
23. Intolerance to Empagliflozin and excipients in Empagliflozin or rather placebo
24. Patients with severe stenosis or regurgitation of the aortic, pulmonary or mitral valve

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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19 participants in 2 patient groups, including a placebo group

Empagliflozin

Experimental group

Description:

Patients will receive empagliflozin 10 mg qd for a period of 30 days.

Treatment:

Drug: Empagliflozin

Placebo

Placebo Comparator group

Description:

Patients of the placebo arm will receive placebo tablets qd for a period of 30 days.

Treatment:

Drug: Placebo