EMPA Acute Heart Failure

Phase 2

Terminated

• Conditions: Acute Heart Failure; Diabetes Mellitus, Type 2
• Interventions: Drug: Placebo; Drug: Empagliflozin

• Registration Number: NCT03554200
• Lead Sponsor: RWTH Aachen University

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.

Study Timeline

• Study First Submitted: 2018-05-17
• Study First Submitted QC: 2018-05-30
• Study Start: 2018-06-11
• Study First Posted: 2018-06-13
• Primary Completion: 2020-10-29
• Study Completion: 2020-10-29
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-25
• Last Update Posted: 2022-10-27

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 19

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Patients of the placebo arm will receive placebo tablets qd for a period of 30 days.
Empagliflozin	Empagliflozin	Patients will receive empagliflozin 10 mg qd for a period of 30 days.

Primary Outcome Measures

Name	Time	Method
effect of Empagliflozin 10mg qd versus placebo on cardiac output in patients with acute heart failure	30 days	by ClearSight System

Secondary Outcome Measures

Name	Time	Method
Oxygen	30 days	delivered (l/min)
Cardio vascular	30 days	24 h heart rate (bpm)
change of microbiome	30 days	stool sample
Hemodynamics	30 days	Stroke volume (ml/beat)
Exercise Capacity	30 days	Hand grip
Blood	30 days	Serum osmolarity, Potassium, Chloride
Clinical judged diuretic requirement	30 days
Effect of Empagliflozin 10 mg daily on Left ventricular systolic function	30 days	ejection fraction
Diuretic response	30 days	Δ weight kg/\[(total i.v. dose)/40mg\]+\[(total oral dose)/80mg)\] furosemide
Patient-reported dyspnea	30 days	visual analogue scale (VAS), 7 point categorical Likert scale
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)
Respiratory rate	30 days	breaths/min
Kidney injury risk score	30 days	by NephroCheck® (defined by TIMP-2 x IGFBP7 in urine)
Peak expiratory flow rate	30 days
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

Trial Locations

Locations (1)

Department of Internal Medicine I RWTH Aachen University Hospital; 🇩🇪 Aachen, NRW, Germany