Acute Heart Failure, Diabetes Mellitus, Type 2
Conditions
Keywords
Empagliflozin, acute heart failure, cardiac output, left ventricular systolic and diastolic function, exercise capacity
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.
Interventions
DRUGEmpagliflozin
Standard of Care + Empagliflozin: 10 mg (tablets) once daily
DRUGPlacebo
Standard of Care + Placebo: Matching Placebo (tablets) once daily
Sponsors
Boehringer Ingelheim
RWTH Aachen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This trial is double-blinded. After randomization neither the patients nor the investigator will be aware of the treatment allocation. Patients assigned to one of the double-blinded treatment will take one tablet Empagliflozin or matching placebo. The tablets will be identical in appearance.
Intervention model description
Single center, prospective, placebo-controlled, double blind, randomized, 2-arm parallel, interventional, exploratory pilot study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| effect of Empagliflozin 10mg qd versus placebo on cardiac output in patients with acute heart failure | 30 days | by ClearSight System |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Exercise Capacity | 30 days | Hand grip |
| Cardio vascular | 30 days | blood pressure (mmHg) |
| Effect of Empagliflozin on systemic quality of life | 30 days | Quality of life questionnaire |
| Effect of Empagliflozin on hospitalization due to cardiovascular causes or readmission for heart failure or renal failure | 30 days | length of initial hospital stay |
| Effect of Empagliflozin on death due to cardiovascular causes | 30 days | days alive and out of hospital |
| Urine | 30 days | 24 h sodium excretion (mmol/day) |
| Body weight | 30 days | body weight (kg) |
| Blood | 30 days | NT-proBNP (ng/l) |
| Respiratory rate | 30 days | breaths/min |
| Hemodynamics | 30 days | Systemic vascular resistance (mmHg⋅min⋅mL-1) |
| Kidney injury risk score | 30 days | by NephroCheck® (defined by TIMP-2 x IGFBP7 in urine) |
| change of microbiome | 30 days | stool sample |
| Patient-reported dyspnea | 30 days | visual analogue scale (VAS), 7 point categorical Likert scale |
| Peak expiratory flow rate | 30 days | — |
| Oxygen | 30 days | Saturation (%) |
| Clinical judged diuretic requirement | 30 days | — |
| Effect of Empagliflozin 10 mg daily on Left ventricular systolic function | 30 days | ejection fraction |
| Effect of Empagliflozin 10 mg daily on Left ventricular diastolic function | 30 days | 2D and 3D parameter global strain rate E by echocardiography and by standardized parameter E/E' and left atrial (LA) volume |
| Diuretic response | 30 days | Δ weight kg/\[(total i.v. dose)/40mg\]+\[(total oral dose)/80mg)\] furosemide |
Countries
Germany
Outcome results
None listed