EMPA Acute Heart Failure

Sponsor

RWTH Aachen University (Other)

Overall Status

Terminated

CT.gov ID

NCT03554200

Collaborator

Boehringer Ingelheim (Industry)

Enrollment

Location

Arms

28.6

Actual Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2 Acute Heart Failure	Drug: Empagliflozin Drug: Placebo	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

19 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Single center, prospective, placebo-controlled, double blind, randomized, 2-arm parallel, interventional, exploratory pilot studySingle center, prospective, placebo-controlled, double blind, randomized, 2-arm parallel, interventional, exploratory pilot study

Masking:

Double (Participant, 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.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 11, 2018

Actual Primary Completion Date :

Oct 29, 2020

Actual Study Completion Date :

Oct 29, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Empagliflozin Patients will receive empagliflozin 10 mg qd for a period of 30 days.	Drug: Empagliflozin Standard of Care + Empagliflozin: 10 mg (tablets) once daily Other Names: Jardiance
Placebo Comparator: Placebo Patients of the placebo arm will receive placebo tablets qd for a period of 30 days.	Drug: Placebo Standard of Care + Placebo: Matching Placebo (tablets) once daily

Arm

Intervention/Treatment

Experimental: Empagliflozin

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

Drug: Empagliflozin

Standard of Care + Empagliflozin: 10 mg (tablets) once daily

Other Names:

Jardiance

Placebo Comparator: Placebo

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

Drug: Placebo

Standard of Care + Placebo: Matching Placebo (tablets) once daily

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Hemodynamics [30 days]
Systemic vascular resistance (mmHg⋅min⋅mL-1)
Hemodynamics [30 days]
Stroke volume (ml/beat)
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)
Cardio vascular [30 days]
24 h heart rate (bpm)
Blood [30 days]
NT-proBNP (ng/l)
Blood [30 days]
cystatin C(mg/dl)
Blood [30 days]
serum levels of Glucose, Glucagon, Insulin, Total-Ketone bodies, Hydroxybutyrate, Aldosterone, Free fatty acidy (mg/dl)
Blood [30 days]
Hemoglobin, Haematocrit, Erythropoietin
Respiratory rate [30 days]
breaths/min
Diuretic response [30 days]
Δ weight kg/[(total i.v. dose)/40mg]+[(total oral dose)/80mg)] furosemide
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 (%)
Oxygen [30 days]
delivered (l/min)
Clinical judged diuretic requirement [30 days]
Blood [30 days]
eGFR
Blood [30 days]
Lactate, pH, HCO3-
Blood [30 days]
Serum osmolarity, Potassium, Chloride
Effecr of Empagliflozin 10 mg daily on Left ventricular systolic function [30 days]
ejection fraction
Effecr 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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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