Acute Decompensated Heart FailurePhase 2EMPAG-HFNCT04049045
Effects of Empagliflozin on Diuresis and Renal Function in Patients With Acute Decompensated Heart Failure
A Phase 2 study testing Empagliflozin 25 mg in people with Acute Decompensated Heart Failure, run by Christian Schulze at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Acute Decompensated Heart Failure
- What is being tested?
- Empagliflozin 25 mg
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteGermany
- Study dates
- 29 Sep 2019to 29 Jun 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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)
Show all 12Show fewer
- 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 )
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department of Internal Medicine I, Jena University Hospital
Jena, 07747
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Acute Decompensated Heart Failure
- Being tested
- Empagliflozin 25 mg, Placebo
- Keywords
- acute decompensated heart failure, empagliflozin, diuresis, renal function
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin 25 mgDrug
Empagliflozin 25 mg film-coated tablets, for oral use administered once daily for 5 days in addition to routinely administered (weight adjusted) intravenous furosemide
PlaceboDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Verum arm | Active comparator | 25 mg tablet of empagliflozin once daily for five days Receives: Drug: Empagliflozin 25 mg |
| Placebo arm | Placebo comparator | one tablet of the matching Placebo once daily for five days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total urinary output (UOP) as measured by daily volume summed up over 5 days
Total UOP as summed over 5 days
Measured: 5 days
Secondary outcomes (7)
Renal function under treatment
Change of creatinine values: increase in creatinine of > 0.3 mg/dl, doubling of serum creatinine, need for renal replacement therapy
Measured: 5 days
Net fluid output
UOP - fluid intake
Measured: 5 days
Worsening or persistent heart failure
NYHA class (New York Heart Association functional heart failure classification)
Measured: 30 days
Intermediate Care (IMC) / Intensive Care Unit (ICU) and hospital length of stay
Duration in days
Measured: 30 days
Liver function
bilirubin, serum aminotransferases, relevant change in coagulation status
Measured: 30 days
Pulmonary function
oxygen saturation without oxygen therapy/ need for oxygen in l/min, presence of rales, changes in chest x-ray (worsening/ improvement/ new infiltration)
Measured: 30 days
Number of patients alive and out of hospital -after 30 days
number of patients
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2019
- Study start29 Sep 2019
- Primary completion30 May 2021
- Study completion29 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Decompensated Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Single-center, prospective, double-blind, placebo-controlled, randomized and interventional exploratory study
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Christian Schulze
- Sponsor type
- University, hospital or other
- Collaborators
- Boehringer Ingelheim, Zentrum für Klinische Studien Jena
- Responsible party
- Sponsor-investigator, Christian Schulze, Jena University Hospital
- Investigators
- Christian Schulze, Prof. Dr., Principal investigator, Department of Internal Medicine I, Jena University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04049045
- Sponsor's protocol ID
- ZKSJ0109
- Acronym
- EMPAG-HF
- Status last verified
- Jul 2021
- First submitted
- 10 Jul 2019
- Last updated
- 3 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 35766022
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Empagliflozin on Diuresis and Renal Function in Patients With Acute Decompensated Heart Failure
- ClinicalTrials.gov ID
- NCT04049045
- Acronym / sponsor ID
- EMPAG-HF / ZKSJ0109
- Conditions
- Acute Decompensated Heart Failure
- Keywords
- acute decompensated heart failure, empagliflozin, diuresis, renal function
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Christian SchulzeUniversity, hospital or other
- Collaborators
- Boehringer Ingelheim, Zentrum für Klinische Studien Jena
- Study start
- 29 Sep 2019 (actual)
- Primary completion
- 30 May 2021 (actual)
- Study completion
- 29 Jun 2021 (actual)
- First posted
- 7 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Single-center, prospective, double-blind, placebo-controlled, randomized and interventional exploratory study
| Arm | Type | Receives |
|---|---|---|
| Verum arm | Active comparator | Drug: Empagliflozin 25 mg25 mg tablet of empagliflozin once daily for five days |
| Placebo arm | Placebo comparator | Drug: Placeboone tablet of the matching Placebo once daily for five days |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Empagliflozin 25 mgEmpagliflozin 25 mg film-coated tablets, for oral use administered once daily for 5 days in addition to routinely administered (weight adjusted) intravenous furosemide | Drug | Verum arm |
| Placebomatching 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 | Drug | Placebo arm |
Primary outcome
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
7 secondary outcomes
Renal function under treatment
Time frame: 5 days
Net fluid output
Time frame: 5 days
Worsening or persistent heart failure
Time frame: 30 days
Intermediate Care (IMC) / Intensive Care Unit (ICU) and hospital length of stay
Time frame: 30 days
Liver function
Time frame: 30 days
Pulmonary function
Time frame: 30 days
Number of patients alive and out of hospital -after 30 days
Time frame: 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2021.
- Derived from this study: PubMed 35766022Schulze 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christian Schulze, Prof. Dr. principal investigator
Department of Internal Medicine I, Jena University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Empagliflozin 25 mg in people with Acute Decompensated Heart Failure, run by Christian Schulze at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total urinary output (UOP) as measured by daily volume summed up over 5 days (time frame: 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04049045, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2021.