Clinical trial NCT03554200: EMPA Acute Heart Failure
Official title: Effect of Empagliflozin on Cardiac Output in Patients With Acute Heart Failure (EMPA Acute Heart Failure)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Acute Heart Failure
Keywords: Empagliflozin
acute heart failure
cardiac output
left ventricular systolic and diastolic function
exercise capacity
Lead sponsor: RWTH Aachen University
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
First posted: 2018-06-13
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single center, prospective, placebo-controlled, double blind, randomized, 2-arm parallel, interventional, exploratory pilot study
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: effect of Empagliflozin 10mg qd versus placebo on cardiac output in patients with acute heart failure
timeFrame: 30 days
Secondary outcomes:
measure: Hemodynamics
timeFrame: 30 days
measure: Hemodynamics
timeFrame: 30 days
measure: Exercise Capacity
timeFrame: 30 days
measure: Cardio vascular
timeFrame: 30 days
measure: Effect of Empagliflozin on systemic quality of life
timeFrame: 30 days
measure: Effect of Empagliflozin on hospitalization due to cardiovascular causes or readmission for heart failure or renal failure
timeFrame: 30 days
measure: Effect of Empagliflozin on death due to cardiovascular causes
timeFrame: 30 days
measure: Urine
timeFrame: 30 days
measure: Body weight
timeFrame: 30 days
measure: Cardio vascular
timeFrame: 30 days
measure: Blood
timeFrame: 30 days
measure: Blood
timeFrame: 30 days
measure: Blood
timeFrame: 30 days
measure: Blood
timeFrame: 30 days
measure: Respiratory rate
timeFrame: 30 days
measure: Diuretic response
timeFrame: 30 days
measure: Kidney injury risk score
timeFrame: 30 days
measure: change of microbiome
timeFrame: 30 days
measure: Patient-reported dyspnea
timeFrame: 30 days
measure: Peak expiratory flow rate
timeFrame: 30 days
measure: Oxygen
timeFrame: 30 days
measure: Oxygen
timeFrame: 30 days
measure: Clinical judged diuretic requirement
timeFrame: 30 days
measure: Blood
timeFrame: 30 days
measure: Blood
timeFrame: 30 days
measure: Blood
timeFrame: 30 days
measure: Effect of Empagliflozin 10 mg daily on Left ventricular systolic function
timeFrame: 30 days
measure: Effect of Empagliflozin 10 mg daily on Left ventricular diastolic function
timeFrame: 30 days
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Department of Internal Medicine I RWTH Aachen University Hospital
state: NRW
Study officials:
References: