Effects of Empagliflozin on Diuresis and Renal Function in Patients With Acute Decompensated Heart Failure (EMPAG-HF)

July 27, 2021 updated by: Christian Schulze

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

If feasible (run-in of patients into the hospital from 08:00 a.m. to 06:00 p.m.) screening/baseline, enrolment, randomization and first dose of empagliflozin should be performed on the same day. In general, but especially in case of other run-in times (e.g. late evening, night and early morning hours) screening/baseline time period should not exceed 12 hours. In case a patient has to spend the night in hospital before randomization can be executed, a time period of up to 16 hours will not be counted as protocol deviation.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Jena, Germany, 07747
        • Department of Internal Medicine I, Jena University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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
  • Previous participation in this trial or recent participation in another clinical trial (within the last 3 months before inclusion, so that medical product/s from previous trial participation/s have been fully washed out )Identification of any causes of heart failure leading to decompensation that needs urgent management (like acute coronary syndrome, severe unstable arrhythmias, mechanical causes, acute pulmonary embolism)
  • 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 )

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Verum arm
25 mg tablet of empagliflozin once daily for five days
Drug: Empagliflozin 25 mg
Empagliflozin 25 mg film-coated tablets, for oral use administered once daily for 5 days in addition to routinely administered (weight adjusted) intravenous furosemide
Placebo Comparator: Placebo arm
one tablet of the matching Placebo once daily for five days
Drug: Placebo
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Total urinary output (UOP) as measured by daily volume summed up over 5 days
Time Frame: 5 days
Total UOP as summed over 5 days
5 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Renal function under treatment
Time Frame: 5 days
Change of creatinine values: increase in creatinine of > 0.3 mg/dl, doubling of serum creatinine, need for renal replacement therapy
5 days
Net fluid output
Time Frame: 5 days
UOP - fluid intake
5 days
Worsening or persistent heart failure
Time Frame: 30 days
NYHA class (New York Heart Association functional heart failure classification)
30 days
Intermediate Care (IMC) / Intensive Care Unit (ICU) and hospital length of stay
Time Frame: 30 days
Duration in days
30 days
Liver function
Time Frame: 30 days
bilirubin, serum aminotransferases, relevant change in coagulation status
30 days
Pulmonary function
Time Frame: 30 days
oxygen saturation without oxygen therapy/ need for oxygen in l/min, presence of rales, changes in chest x-ray (worsening/ improvement/ new infiltration)
30 days
Number of patients alive and out of hospital -after 30 days
Time Frame: 30 days
number of patients
30 days

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Safety Outcome: Number of Adverse Events and Serious Adverse Events including MedDRA-SAE Preferred Terms and SOCs in both groups
Time Frame: 30 days
Listing of all adverse events and serious adverse events, laboratory parameters as far as not efficacy parameters
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Christian Schulze

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Boehringer Ingelheim
Zentrum für Klinische Studien Jena

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Christian Schulze, Prof. Dr., Department of Internal Medicine I, Jena University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 29, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 30, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 29, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 10, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 6, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 7, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 3, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 27, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ZKSJ0109

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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