Effects of Empagliflozin on Diuresis and Renal Function in Patients With Acute Decompensated Heart Failure

NCT04049045 | Completed Phase 2 DMC

• 1 other identifier: ZKSJ0109
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Heart failure is the most common hospital admission diagnosis and shows increasing incidence and prevalence in Germany, the United States and worldwide. Improvements in the primary treatment conditions for e.g. myocardial infarction and reduced primary mortality has resulted in an increasing group of patients with secondary cardiac abnormalities including chronic heart failure. Progressive cardiac dysfunction and failure are associated with exercise intolerance, volume retention, nocturia, dyspnoea among others. The most severe progression of heart failure is cardiac decompensation (also called: acute heart failure) and cardiogenic shock. Volume retention, abnormal renal function and diuretic resistance are hallmarks of this clinical phenotype. Currently, the only available treatment is diuresis through various combinations of diuretics and the addition of cardiac inotropes when cardiac hypoperfusion is documented. Patients with acute decompensated heart failure (ADHF) often develop a state of diuretic resistance characterized by a need of rising dosages of diuretics for adequate diuresis and urine production. ADHF patients also show metabolic abnormalities including insulin resistance or type 2 diabetes mellitus. Empagliflozin is a potent and selective inhibitor of the sodium glucose cotransporter 2 (SGLT2) used in the treatment of type 2 diabetes. By inhibiting SGLT2, empagliflozin reduces renal glucose reabsorption and increases urinary glucose excretion. In addition to reducing hyperglycaemia, empagliflozin is associated with osmotic diuresis, reductions in weight and blood pressure without increases in heart rate, and has favourable effects on markers of arterial stiffness and vascular resistance. The investigators propose a single center exploratory study to test the hypothesis that the application of empagliflozin in addition to standard diuretic regimens increases urine output, decreases the need for further acceleration of diuretic regimens, and positively influences renal function as well as metabolism including insulin resistance in ADHF patients. Thereby, empagliflozin may be effective in the prevention of complex cardio metabolic alterations involved in ADHF.

Conditions

Acute Decompensated Heart Failure

Keywords

acute decompensated heart failure; empagliflozin; diuresis; renal function

Outcome Measures

Primary Outcomes (1)

• Total urinary output (UOP) as measured by daily volume summed up over 5 days

  Total UOP as summed over 5 days

  5 days

Secondary Outcomes (7)

• Renal function under treatment

  5 days

• Net fluid output

  5 days

• Worsening or persistent heart failure

  30 days

• Intermediate Care (IMC) / Intensive Care Unit (ICU) and hospital length of stay

  30 days

• Liver function

  30 days

Other Outcomes (1)

• Safety Outcome: Number of Adverse Events and Serious Adverse Events including MedDRA-SAE Preferred Terms and SOCs in both groups

  30 days

Study Arms (2)

Verum arm

ACTIVE COMPARATOR

25 mg tablet of empagliflozin once daily for five days

Drug: Empagliflozin 25 mg

Placebo arm

PLACEBO COMPARATOR

one tablet of the matching Placebo once daily for five days

Drug: Placebo

Interventions

Empagliflozin 25 mg DRUG

Empagliflozin 25 mg film-coated tablets, for oral use administered once daily for 5 days in addition to routinely administered (weight adjusted) intravenous furosemide

Verum arm

Placebo DRUG

matching Placebo, film-coated tablets, for oral use, matching to investigational product Jardiance® administered once daily for 5 days in addition to routinely administered (weight adjusted) intravenous furosemide

Placebo arm

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients (age between 18-85 years) with acute decompensated heart failure (HF).
• Brain Natriuretic Peptide (BNP) \>100 pg/ml, or N-terminal pro-BNP (NT-proBNP)\>300 pg/ml as defined by current clinical guidelines for the diagnosis of acute decompensated HF (European Society of Cardiology 2016 HF guideline)
• Patients with diabetes mellitus type 2 or impaired glucose tolerance as defined by current clinical guidelines (German and International Diabetes Society 2016: HbA1c\>6.5 % (upper limit for this clinical trial 12 %) or fasting glucose \>7.0 mmol/l or any incidental glucose level \>11.1 mmol/l or abnormal oral glucose tolerance test with 2h plasma glucose \>7.8 mmol/l) or on antidiabetic medication or antidiabetic diet or patients with normal Glucose tolerance
• Patients without cognitive impairment, i.e. they must be capable of understanding the nature, significance and implications of the clinical trial and to form a rational intention in the light of the facts
• Written informed consent obtained
• For women with childbearing potential (until 2 years after menopause):
• Negative pregnancy test
• regular and correct use of a highly effective contraceptive method with an error rate of \<1% per year (e.g. combined (estrogen and progesteron) hormonal contraception (oral, intravaginal, transdermal), progesteron-only hormonal contraception (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS) tubal ligation (female sterilization), hormon donating intrauterine device ("hormonal spiral"), double barrier methods, sexual abstinence, vasectomy of the partner)

You may not qualify if:

• Type 1 diabetes mellitus
• Chronic Kidney Disease (CKD) with eGFR\< 30 ml/min, or end-stage renal failure with the need for chronic dialysis treatment
• Acute kidney injury (AKI) ≥ Acute Kidney Injury Network (AKIN) stage 2 or requiring dialysis treatment
• Current medication with SGLT-2 inhibitors
• Known intolerance or hypersensitivity to the active substance empagliflozin, lactose or any other of the excipients listed in section 6.1. of the summary of product characteristics (SmPC). A contraindication or intolerance to furosemide
• Acute heart failure without signs of congestion ("dry" patient)
• Indication for urgent coronary angiography or any planned administration of a iodine based contrast agent within the next 6 days
• Need for hemofiltration or any other form of extracorporeal therapy
• Planned surgery
• Incapacity to understand and / or to provide written informed consent
• Ongoing reported alcohol abuse (daily alcohol intake of more than 2 drinks (liquor, beer or wine) in men and 1 drink in women, corresponding to 12/24 g of pure alcohol per day women / men and/ or obvious alcoholisation of the patient during screening )

Sponsors & Collaborators

• Christian Schulze: lead
• Boehringer Ingelheim: collaborator
• Zentrum für Klinische Studien Jena: collaborator

Study Sites (1)

Department of Internal Medicine I, Jena University Hospital

Jena, 07747, Germany

Location

Related Publications (1)

• Schulze PC, Bogoviku J, Westphal J, Aftanski P, Haertel F, Grund S, von Haehling S, Schumacher U, Mobius-Winkler S, Busch M. Effects of Early Empagliflozin Initiation on Diuresis and Kidney Function in Patients With Acute Decompensated Heart Failure (EMPAG-HF). Circulation. 2022 Jul 26;146(4):289-298. doi: 10.1161/CIRCULATIONAHA.122.059038. Epub 2022 Jun 29.

  PMID: 35766022 DERIVED

MeSH Terms

Interventions

empagliflozin

Study Officials

• Christian Schulze, Prof. Dr.

  Department of Internal Medicine I, Jena University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: There will be two trial medications, the licensed medicinal product empagliflozin, trade name Jardiance®, 25 mg and matching placebo tablets. The placebo tablets will be indistinguishable by appearance, taste, smell, weight from the investigational product. Both will be stored in plastic containers containing 30 tablets each.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med. P. Christian Schulze

Model Details: Single-center, prospective, double-blind, placebo-controlled, randomized and interventional exploratory study

Study Record Dates

• First Submitted: July 10, 2019
• First Posted: August 7, 2019
• Study Start: September 29, 2019
• Primary Completion: May 30, 2021
• Study Completion: June 29, 2021
• Last Updated: August 3, 2021

Record last verified: 2021-07

Locations

DE (1)