EMPA Acute Heart Failure

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Effect of Empagliflozin on Cardiac Output in Patients With Acute Heart Failure (EMPA Acute Heart Failure)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03554200
• Other study ID #: 15-156
• Secondary ID: 2017-002695-45
• Status: Terminated
• Phase: Phase 2
• Start date: June 11, 2018
• Est. completion date: October 29, 2020

Study information

• Verified date: October 2022
• Source: RWTH Aachen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 19
• Est. completion date: October 29, 2020
• Est. primary completion date: October 29, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Heart Failure
• Diabetes Mellitus, Type 2
• Heart Failure

Intervention

Drug:
• Empagliflozin
Standard of Care + Empagliflozin: 10 mg (tablets) once daily
• Placebo
Standard of Care + Placebo: Matching Placebo (tablets) once daily

Locations

Country	Name	City	State
Germany	Department of Internal Medicine I RWTH Aachen University Hospital	Aachen	NRW

Sponsors (2)

Lead Sponsor	Collaborator
RWTH Aachen University	Boehringer Ingelheim

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	effect of Empagliflozin 10mg qd versus placebo on cardiac output in patients with acute heart failure	by ClearSight System	30 days
Secondary	Hemodynamics	Systemic vascular resistance (mmHg·min·mL-1)	30 days
Secondary	Hemodynamics	Stroke volume (ml/beat)	30 days
Secondary	Exercise Capacity	Hand grip	30 days
Secondary	Cardio vascular	blood pressure (mmHg)	30 days
Secondary	Effect of Empagliflozin on systemic quality of life	Quality of life questionnaire	30 days
Secondary	Effect of Empagliflozin on hospitalization due to cardiovascular causes or readmission for heart failure or renal failure	length of initial hospital stay	30 days
Secondary	Effect of Empagliflozin on death due to cardiovascular causes	days alive and out of hospital	30 days
Secondary	Urine	24 h sodium excretion (mmol/day)	30 days
Secondary	Body weight	body weight (kg)	30 days
Secondary	Cardio vascular	24 h heart rate (bpm)	30 days
Secondary	Blood	NT-proBNP (ng/l)	30 days
Secondary	Blood	cystatin C(mg/dl)	30 days
Secondary	Blood	serum levels of Glucose, Glucagon, Insulin, Total-Ketone bodies, Hydroxybutyrate, Aldosterone, Free fatty acidy (mg/dl)	30 days
Secondary	Blood	Hemoglobin, Haematocrit, Erythropoietin	30 days
Secondary	Respiratory rate	breaths/min	30 days
Secondary	Diuretic response	? weight kg/[(total i.v. dose)/40mg]+[(total oral dose)/80mg)] furosemide	30 days
Secondary	Kidney injury risk score	by NephroCheck® (defined by TIMP-2 x IGFBP7 in urine)	30 days
Secondary	change of microbiome	stool sample	30 days
Secondary	Patient-reported dyspnea	visual analogue scale (VAS), 7 point categorical Likert scale	30 days
Secondary	Peak expiratory flow rate		30 days
Secondary	Oxygen	Saturation (%)	30 days
Secondary	Oxygen	delivered (l/min)	30 days
Secondary	Clinical judged diuretic requirement		30 days
Secondary	Blood	eGFR	30 days
Secondary	Blood	Lactate, pH, HCO3-	30 days
Secondary	Blood	Serum osmolarity, Potassium, Chloride	30 days
Secondary	Effect of Empagliflozin 10 mg daily on Left ventricular systolic function	ejection fraction	30 days
Secondary	Effect of Empagliflozin 10 mg daily on Left ventricular diastolic function	2D and 3D parameter global strain rate E by echocardiography and by standardized parameter E/E' and left atrial (LA) volume	30 days