Heart FailurePhase 4NCT05584319
EMPAGUM: Effects of Empagliflozin on Gut Microbiota in Heart Failure With a Preserved Ejection Fraction
A Phase 4 study testing Empagliflozin 10 Mg in people with Heart Failure and Heart Failure With Preserved Ejection Fraction, run by Zhijun Sun at 1 site in China.
Trial summary
Empagliflozin was recommended for patients with heart failure with reduced ejection fraction (HFrEF) in 2021 European Society of Cardiology (ESC) guidelines (Class of Recommendation Ia) and patients with heart failure with preserved ejection fraction (HFpEF) in 2022 American Heart Association (AHA) guidelines (Class… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Heart Failure With Preserved Ejection Fraction
- What is being tested?
- Empagliflozin 10 Mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- 15 Dec 2022to Oct 2025
- Phase
- Phase 4
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years old, BMI 18.5-27.9kg/m.
- Patients with heart failure and EF>40%, New York Heart Association classification ( NYHA) class II-IV and evidence of structural heart disease (i.e. left ventricular hypertrophy or left atrial enlargement by the recent echocardiogram within the last 12 months before enrollment).
- NT-proBNP≥300 pg/ml for patients without AF, or ≥600 pg/ml for patients with atrial fibrillation (AF).
- Signed and dated written informed consent form (ICF)
Who cannot join
- 1.Current use or prior use of a SGLT-2 inhibitor in 3 months. 2.Patients with type 1 diabetes mellitus. 3.History of ketoacidosis. 4.Impaired renal function with estimated glomerular filtration rate (eGFR)<20ml/min/1.73m².
- 5.On a diet or with a recent diet plan adjustment. 6.Have gastrointestinal diseases which in active stages (e.g. malabsorptive conditions such as irritable bowel syndrome, coeliac).
- 7.Combination of sever infectious diseases (e.g. Severe myocarditis, severe pneumonia, and severe urinary tract infection ).
- 8.Acute decompensated heart failure. 9.Severe diseases in other systems (e.g. severe liver insufficiency, moderate-severe anemia, malignant tumors, hematological diseases).
- 10.Known or suspected allergy to the active or inactive ingredients of the drug under study.
- 11.Admitted percutaneous coronary intervention (PCI), or cardiac surgery, cardiac resynchronization (CRT), or other surgery within the past 90 days.
- 12.Arranging to receive cardiovascular revascularization (percutaneous intervention or surgery) or major heart surgery (coronary artery bypass transplantation, valve replacement, ventricular aids, heart transplantation, CRT or any other surgery requiring thoracotomy or transcatheter aortic valve replacement) in 30 days.
- 13.Symptomatic hypotension with systolic pressure ≤ 90mmHg. 14.Systolic pressure ≥ 180mmHg which cannot be controlled with drugs. 15.Currently enrolled in another investigational device or drug trial. 16.Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
Trial locations and contacts
1 site in 1 country.
About this study
Empagliflozin was recommended for patients with heart failure with reduced ejection fraction (HFrEF) in 2021 European Society of Cardiology (ESC) guidelines (Class of Recommendation Ia) and patients with heart failure with preserved ejection fraction (HFpEF) in 2022 American Heart Association (AHA) guidelines (Class of Recommendation IIa). However, the physiopathologic mechanisms in its effects on HFpEF are not clear. Studies illustrate that gut microbiota plays an essential role in the progress of the heart failure. Studies on mice found that sodium-glucose cotransporter-2 inhibitors (sglt-2i) could affect the intestinal microbiota in mice. The purpose of this study is to clarify the changes of gut microbiota in the patients with HFpEF taking Empagliflozin and explore the role of gut microbiota in this process.
Read the detailed description
As one of the most important cardiovascular diseases, heart failure is characterized by high incidence and high fatality rate. Heart failure with reduced ejection fraction (HFrEF) has been widely researched for decades and its clinical treatments have been improved remarkably. However, patients with non-reduced ejection fraction accounts for more than 50% of the whole group, especially patients with HFpEF. As for its complicated mechanism as well as normally less serious symptoms, its clinical treatments were not detailed enough before.
Patients with heart failure often have decreased cardiac output combined with peripheral circulation congestion, leading to intestinal ischemia and edema. In this case, the intestinal barrier function is weakened, the intestinal wall permeability increases, the bacterial flora is displaced, and more harmful metabolites would also enter the blood circulation through the weakened intestinal mucosal barrier, inspiring more inflammatory substances and aggravating the states of heart failure.
Empagliflozin is a sodium-glucose transporter 2 (sglt-2) inhibitor, which can inhibit the reabsorption of glucose in the kidney, discharge excessive glucose from the urine, and reduce blood glucose. It is a new type of hypoglycemic drugs. However, as the study progressed, the effect of sglt-2 inhibitors extends. In fundamental and animal trials, sglt-2 inhibitors were found to reduce sodium uptake, inhibit NO synthesis, improve cardiac energy metabolism, and inhibit cardiac inflammation. In the 2021 ESC heart failure guidelines, sglt-2 inhibitors have been included in the "new quadruple" therapy to target patients with HFrEF. Moreover, in the newly published EMPEROR-preserved study, Empagliflozin still achieved very good efficacy in ejection fraction-preserved heart failure, reducing the composite endpoint event by 21%. The mechanisms by which sglt-2 inhibitors act on heart failure have not been fully resolved, and in basic studies, sglt-2 inhibitors were found to affect the intestinal microbiota in mice.
Based on the emerging importance of intestinal microbiota in the process of heart failure, and the impacts of sglt-2 inhibitors on intestinal microbiota and heart failure. It is necessary to clarify the changes of gut microbiota in the patients with non-reduced ejection fraction taking Empagliflozin and explore the role of gut microbiota in this process.
- Being tested
- Empagliflozin 10 Mg
- Keywords
- Heart Failure, Gut Microbiota, SGLT2 Inhibitor, Myocardial Fibrosis, Short-chain Fatty Acids, Derived Metabolite
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin 10 MgDrug
Also called Empagliflozin
subjects in Empagliflozin group takes Empagliflozin 10mg per day
| Study group | Role | What they receive |
|---|---|---|
| Empagliflozin group | Experimental | Subjects in Empagliflozin group take in 10Mg Empagliflozin per day. Receives: Drug: Empagliflozin 10 Mg |
| Blank control group | No intervention | Subjects in Blank control group will not receive Empagliflozin or other sglt-2 inhibitors. |
What is being measured
The primary outcome is the main question the study is designed to answer.
intestinal microbiota diversity
the changes of Alpha diversity and Beta diversity of intestinal microbiota in samples
Measured: 6 months
Secondary outcomes (4)
Major Adverse Cardiovascular Events (MACE)
Mace is defined as cardiovascular death and cardiovascular related readmission
Measured: 6 months
N-terminal prohormone of B-type natriuretic peptide ( NT-proBNP )
Changes of NT-proBNP in 6 months
Measured: 6 months
soluble suppression of tumorigenicity 2 (sST2）
Changes of sST2 in 6 months
Measured: 6 months
serum SCFAs level
Changes of serum SCFAs level in 6 months
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2022
- Study start15 Dec 2022 (estimated)
- Primary completionOct 2024 (estimated)
- Study completionOct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhijun Sun
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Zhijun Sun, Shengjing Hospital
- Investigators
- 10027 10027, Principal investigator, Shengjing Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05584319
- Sponsor's protocol ID
- 2022PS999K
- Status last verified
- Dec 2022
- First submitted
- 8 Oct 2022
- Last updated
- 23 Dec 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- EMPAGUM: Effects of Empagliflozin on Gut Microbiota in Heart Failure With a Preserved Ejection Fraction
- ClinicalTrials.gov ID
- NCT05584319
- Acronym / sponsor ID
- 2022PS999K
- Keywords
- Heart Failure, Gut Microbiota, SGLT2 Inhibitor, Myocardial Fibrosis, Short-chain Fatty Acids, Derived Metabolite
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Zhijun SunUniversity, hospital or other
- Study start
- 15 Dec 2022 (estimated)
- Primary completion
- Oct 2024 (estimated)
- Study completion
- Oct 2025 (estimated)
- First posted
- 18 Oct 2022 (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.
Empagliflozin was recommended for patients with heart failure with reduced ejection fraction (HFrEF) in 2021 European Society of Cardiology (ESC) guidelines (Class of Recommendation Ia) and patients with heart failure with preserved ejection fraction (HFpEF) in 2022 American Heart Association (AHA) guidelines (Class of Recommendation IIa). However, the physiopathologic mechanisms in its effects on HFpEF are not clear. Studies illustrate that gut microbiota plays an essential role in the progress of the heart failure. Studies on mice found that sodium-glucose cotransporter-2 inhibitors (sglt-2i) could affect the intestinal microbiota in mice. The purpose of this study is to clarify the changes of gut microbiota in the patients with HFpEF taking Empagliflozin and explore the role of gut microbiota in this process.
Detailed description
As one of the most important cardiovascular diseases, heart failure is characterized by high incidence and high fatality rate. Heart failure with reduced ejection fraction (HFrEF) has been widely researched for decades and its clinical treatments have been improved remarkably. However, patients with non-reduced ejection fraction accounts for more than 50% of the whole group, especially patients with HFpEF. As for its complicated mechanism as well as normally less serious symptoms, its clinical treatments were not detailed enough before.
Patients with heart failure often have decreased cardiac output combined with peripheral circulation congestion, leading to intestinal ischemia and edema. In this case, the intestinal barrier function is weakened, the intestinal wall permeability increases, the bacterial flora is displaced, and more harmful metabolites would also enter the blood circulation through the weakened intestinal mucosal barrier, inspiring more inflammatory substances and aggravating the states of heart failure.
Empagliflozin is a sodium-glucose transporter 2 (sglt-2) inhibitor, which can inhibit the reabsorption of glucose in the kidney, discharge excessive glucose from the urine, and reduce blood glucose. It is a new type of hypoglycemic drugs. However, as the study progressed, the effect of sglt-2 inhibitors extends. In fundamental and animal trials, sglt-2 inhibitors were found to reduce sodium uptake, inhibit NO synthesis, improve cardiac energy metabolism, and inhibit cardiac inflammation. In the 2021 ESC heart failure guidelines, sglt-2 inhibitors have been included in the "new quadruple" therapy to target patients with HFrEF. Moreover, in the newly published EMPEROR-preserved study, Empagliflozin still achieved very good efficacy in ejection fraction-preserved heart failure, reducing the composite endpoint event by 21%. The mechanisms by which sglt-2 inhibitors act on heart failure have not been fully resolved, and in basic studies, sglt-2 inhibitors were found to affect the intestinal microbiota in mice.
Based on the emerging importance of intestinal microbiota in the process of heart failure, and the impacts of sglt-2 inhibitors on intestinal microbiota and heart failure. It is necessary to clarify the changes of gut microbiota in the patients with non-reduced ejection fraction taking Empagliflozin and explore the role of gut microbiota in this process.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Empagliflozin group | Experimental | Drug: Empagliflozin 10 MgSubjects in Empagliflozin group take in 10Mg Empagliflozin per day. |
| Blank control group | No intervention | –Subjects in Blank control group will not receive Empagliflozin or other sglt-2 inhibitors. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age ≥ 18 years old, BMI 18.5-27.9kg/m.
- Patients with heart failure and EF>40%, New York Heart Association classification ( NYHA) class II-IV and evidence of structural heart disease (i.e. left ventricular hypertrophy or left atrial enlargement by the recent echocardiogram within the last 12 months before enrollment).
- NT-proBNP≥300 pg/ml for patients without AF, or ≥600 pg/ml for patients with atrial fibrillation (AF).
- Signed and dated written informed consent form (ICF)
Key exclusion criteria (8 listed)
- 1.Current use or prior use of a SGLT-2 inhibitor in 3 months. 2.Patients with type 1 diabetes mellitus. 3.History of ketoacidosis. 4.Impaired renal function with estimated glomerular filtration rate (eGFR)<20ml/min/1.73m².
- 5.On a diet or with a recent diet plan adjustment. 6.Have gastrointestinal diseases which in active stages (e.g. malabsorptive conditions such as irritable bowel syndrome, coeliac).
- 7.Combination of sever infectious diseases (e.g. Severe myocarditis, severe pneumonia, and severe urinary tract infection ).
- 8.Acute decompensated heart failure. 9.Severe diseases in other systems (e.g. severe liver insufficiency, moderate-severe anemia, malignant tumors, hematological diseases).
- 10.Known or suspected allergy to the active or inactive ingredients of the drug under study.
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 10 MgAlso: Empagliflozinsubjects in Empagliflozin group takes Empagliflozin 10mg per day | Drug | Empagliflozin group |
Primary outcome
intestinal microbiota diversity
Time frame: 6 months
the changes of Alpha diversity and Beta diversity of intestinal microbiota in samples
4 secondary outcomes
Major Adverse Cardiovascular Events (MACE)
Time frame: 6 months
N-terminal prohormone of B-type natriuretic peptide ( NT-proBNP )
Time frame: 6 months
soluble suppression of tumorigenicity 2 (sST2）
Time frame: 6 months
serum SCFAs level
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2022.
- Individual participant dataSharing planned: No
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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.
10027 10027 principal investigator
Shengjing Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Empagliflozin 10 Mg in people with Heart Failure and Heart Failure With Preserved Ejection Fraction, run by Zhijun Sun at 1 site in China.
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 4 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 23 Dec 2022. 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 China. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
intestinal microbiota diversity (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Dec 2022.