Heart Failure With Preserved Ejection FractionPhase 4NCT06046612
Empagliflozin for Peripheral Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction
A Phase 4 study testing Participants receive 10mg Empaglifozin once daily on prescription from their treating physician. This is not an intervention in this trial, but part of their normal HFpEF treatment in people with Heart Failure With Preserved Ejection Fraction and Microvascular Dysfunction, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
The goal of this low-intervention clinical trial is to learn about the effect of the drug Empagliflozin in patients with heart failure with preserved ejection fraction. The main questions it aims to answer are: What is the effect of treatment with Empagliflozin after 3 months on peripheral microvascular function Do… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure With Preserved Ejection Fraction, Microvascular Dysfunction
- What is being tested?
- Participants receive 10mg Empaglifozin once daily on prescription from their treating physician. This is not an intervention in this trial, but part of their normal HFpEF treatment
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteNetherlands
- Study dates
- 13 Feb 2023to 13 Feb 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
- HFpEF diagnosis according to the ESC 2021 Guidelines for the diagnosis and treatment of acute and chronic heart failure Symptoms and signs of HF LVEF ≥ 50% (on any imaging modality) Objective evidence of cardiac structural and/or functional abnormalities consistent with the presence of LV diastolic dysfunction/ raised LV filling pressures, including raised natriuretic peptides (table 1) OR invasively measured pulmonary capillary wedge pressure (PCWP) of >15 mmHg (at rest) or ≥25 mmHg (with exercise) or left ventricular end diastolic pressure ≥ 16 mmhg (at rest).
- Ability to understand and speak the Dutch language
- Treatment with empagliflozin 10mg once daily is planned to be started by the treating physician
- Signed informed consent
Who cannot join
- Unable or unwilling to sign informed consent
- Under 18 years of age
- Contra-indication to the use of empagliflozin Severe kidney disease (Glomerular filtration rate< 20 ml/min) Severe liver insufficiency Recent (<12 months) or planned major surgery (Including coronary artery bypass grafting, cardiac valve replacement) Severe acute disease (< 12 months) (Including acute coronary syndrome, TIA/CVA) Pregnancy
- Use of empagliflozin or other SGLT-2 inhibitor at baseline
- Known hypersensitivity to empagliflozin, acetylcholine, sodium nitroprusside or insulin
- Insulin dependent patients (Fasting conditions cause a risk of ketoacidosis in these patients).
Show all 9Show fewer
- Subjects currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study.
- Any condition that interferes with the correct execution of the LASCA measurements (patient is unable to keep arms motionless during the measurements, any condition that does not allow disposables to be attached to the forearm skin)
- Any other reason that makes it undesirable for patient to use empagliflozin according to the researcher / treating physician
Trial locations and contacts
1 site in 1 country.
Vanessa PM van Empel, Dr. contact
Netherlands1 site, 1 recruiting
- Recruiting
Maastricht University Hospital
Maastricht, Limburg, 6229 HX
Sanne GJ Mourmans, Drs, +31433871612, sanne.mourmans@mumc.nl
Vanessa PM van Empel, Dr, vanessa.van.empel@mumc.nl
About this study
Official title: The Effect of Empagliflozin on Peripheral Microvascular Dysfunction in Heart Failure With
The goal of this low-intervention clinical trial is to learn about the effect of the drug Empagliflozin in patients with heart failure with preserved ejection fraction.
The main questions it aims to answer are:
Read more
- What is the effect of treatment with Empagliflozin after 3 months on peripheral microvascular function
- Do clinical correlates for worse microvascular function exist, and thus identify patients that could possibly benefit most from empagliflozin treatment
Patients will use Empagliflozin, prescribed by their treating physician. Before the start of treatment and after 3 months they will be asked to
- Fill out a quality of life questionnaire
- Draw 4 tubes of blood
- Undergo non-invasive measurement of the blood flow of the microvasculature in the forearm (using laser speckle contrast analysis)
Read the detailed description
Heart failure (HF) with preserved ejection fraction (HFpEF), is an important public health problem with a poor prognosis and many people are affected by it. Microvascular dysfunction (MVD) is thought to play an important role in this complex syndrome. MVD may lead to disease progression in HFpEF. For the past years the main focus of HFpEF treatment has been on symptom relieve and diagnosing and treating co-occurring disease, such as hypertension or diabetes. Recently, the sodium-glucose co-transporter 2 (SGLT-2) inhibitor Empagliflozin was suggested to be added to this list of treatments. This drug was proven to reduce the combined risk of cardiovascular death or HF hospitalization in HFpEF patients in the EMPEROR-PRESERVED trial. Preclinical studies have proposed an important role for microvascular function in the mechanism of action of empagliflozin in HFpEF. The microvasculature may also play an important role in the etiology of HFpEF.
The microcirculation in the skin is accessible and suitable for analysis of microvascular function. Laser speckle contrast analysis (LASCA) is a relatively new and non-invasive analysis that measures the blood flow in the skin microvasculature using several stimuli.
In HFpEF patients no clinical research has been conducted to evaluate the effect of Empagliflozin on MVD, despite its seemingly important role in the HFpEF etiology. We hypothesize that empagliflozin improves microvascular function in HFpEF patients. Understanding of the effects of this important drug in the treatment of HFpEF is essential to optimize its use in this growing population. Key clinical determinants may exist that improve our ability to determine which patients at what disease stage can specifically benefit from this intervention. The patients with the strongest improvement in MVD during treatment with Empagliflozin might benefit most regarding cardiac function or wellbeing.
- Being tested
- Participants receive 10mg Empaglifozin once daily on prescription from their treating physician. This is not an intervention in this trial, but part of their normal HFpEF treatment
- Keywords
- Heart failure, Empagliflozin, Jardiance, microvascular disease, microvascular function
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Participants receive 10mg Empaglifozin once daily on prescription from their treating physician. This is not an intervention in this trial, but part of their normal HFpEF treatmentDrug
Also called Jardiance
The investigational medicinal product investigated in this trial (empagliflozin) is authorised for use in the European Union by the European Medicines Agency and will be used in accordance with the terms of the marketing authorization. The treating physician (cardiologist) will determine the indication for empagliflozin use, discuss the benefits and risks with the patient, prescribe the drug, and provide follow up after starting the drug, according to normal clinical practice. The study participants are not assigned to a particular therapeutic strategy decided by the clinical trial protocol.
| Study group | Role | What they receive |
|---|---|---|
| heart failure with preserved ejection fraction | Experimental | Empagliflozin 10mg, tablet, once daily Receives: Drug: Participants receive 10mg Empaglifozin once daily on prescription from their treating physician. This is not an intervention in this trial, but part of their normal HFpEF treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cutaneous vascular conductance (CVC)
Skin blood flow (arbitrary perfusion units, APU) is divided by the mean arterial pressure to yield the CVC.
Measured: Change from baseline to 3 months
Secondary outcomes (4)
baseline bloodflow and area under the curve
as measured by LASCA
Measured: Change from baseline to after 3 months
Serum ketone levels in mmol/L
Serum ketone levels in mmol/L
Measured: Change from baseline to after 3 months
EQ5D-5L questionnaire score
index value, ranging from 1 to -0.5. a higher value is a better outcome analogue scale and single index value
Measured: Change from baseline to 3 months
EQ5D-5L questionnaire score
visual analogue scale, ranging from 1 to 100, a higher value is a better outcome
Measured: Change from baseline to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2023
- Study start13 Feb 2023
- Primary completion13 Aug 2024 (estimated)
- Study completion13 Feb 2025 (estimated)
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 Heart Failure With Preserved Ejection FractionStudies 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
- Not applicable
- Intervention model
- Single group
- Model description
- Participants receive 10mg Empaglifozin once daily on prescription from their treating physician. This is not an intervention in this trial, but part of their normal HFpEF treatment. At the start of the study patients will undergo the LASCA measurements. A very small amount of acetylcholine, nitroprusside and insulin will be applied to the skin of the forearm, to stimulate the bloodflow during LASCA. After 3 months of use of Empagliflozin the LASCA measurement will be repeated. Furthermore, at each visit 4 tubes of blood will be drawn for biobanking, and patients will be asked to fill out a quality of life questionnaire. During the trial, patients will be monitored in routine clinical care as indicated by their treating physician.
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06046612
- Sponsor's protocol ID
- 20225016824500
- Status last verified
- Sep 2023
- First submitted
- 12 Apr 2023
- Last updated
- 21 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Mourmans SGJ, Achten A, Hermans R, Scheepers MJE, D'Alessandro E, Swennen G, Woudstra J, Appelman Y, Goor HV, Schalkwijk C, Knackstedt C, Weerts J, Eringa EC, van Empel VPM. The effect of empagliflozin on peripheral microvascular dysfunction in patients with heart failure with preserved ejection fraction. Cardiovasc Diabetol. 2025 Apr 25;24(1):182. doi: 10.1186/s12933-025-02679-8.
PubMed 40281528
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Empagliflozin on Peripheral Microvascular Dysfunction in Heart Failure With
- ClinicalTrials.gov ID
- NCT06046612
- Acronym / sponsor ID
- 20225016824500
- Keywords
- Heart failure, Empagliflozin, Jardiance, microvascular disease, microvascular function
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Study start
- 13 Feb 2023 (actual)
- Primary completion
- 13 Aug 2024 (estimated)
- Study completion
- 13 Feb 2025 (estimated)
- First posted
- 21 Sep 2023 (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.
The goal of this low-intervention clinical trial is to learn about the effect of the drug Empagliflozin in patients with heart failure with preserved ejection fraction.
The main questions it aims to answer are:
- What is the effect of treatment with Empagliflozin after 3 months on peripheral microvascular function
- Do clinical correlates for worse microvascular function exist, and thus identify patients that could possibly benefit most from empagliflozin treatment
Patients will use Empagliflozin, prescribed by their treating physician. Before the start of treatment and after 3 months they will be asked to
- Fill out a quality of life questionnaire
- Draw 4 tubes of blood
- Undergo non-invasive measurement of the blood flow of the microvasculature in the forearm (using laser speckle contrast analysis)
Detailed description
Heart failure (HF) with preserved ejection fraction (HFpEF), is an important public health problem with a poor prognosis and many people are affected by it. Microvascular dysfunction (MVD) is thought to play an important role in this complex syndrome. MVD may lead to disease progression in HFpEF. For the past years the main focus of HFpEF treatment has been on symptom relieve and diagnosing and treating co-occurring disease, such as hypertension or diabetes. Recently, the sodium-glucose co-transporter 2 (SGLT-2) inhibitor Empagliflozin was suggested to be added to this list of treatments. This drug was proven to reduce the combined risk of cardiovascular death or HF hospitalization in HFpEF patients in the EMPEROR-PRESERVED trial. Preclinical studies have proposed an important role for microvascular function in the mechanism of action of empagliflozin in HFpEF. The microvasculature may also play an important role in the etiology of HFpEF.
The microcirculation in the skin is accessible and suitable for analysis of microvascular function. Laser speckle contrast analysis (LASCA) is a relatively new and non-invasive analysis that measures the blood flow in the skin microvasculature using several stimuli.
In HFpEF patients no clinical research has been conducted to evaluate the effect of Empagliflozin on MVD, despite its seemingly important role in the HFpEF etiology. We hypothesize that empagliflozin improves microvascular function in HFpEF patients. Understanding of the effects of this important drug in the treatment of HFpEF is essential to optimize its use in this growing population. Key clinical determinants may exist that improve our ability to determine which patients at what disease stage can specifically benefit from this intervention. The patients with the strongest improvement in MVD during treatment with Empagliflozin might benefit most regarding cardiac function or wellbeing.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Participants receive 10mg Empaglifozin once daily on prescription from their treating physician. This is not an intervention in this trial, but part of their normal HFpEF treatment. At the start of the study patients will undergo the LASCA measurements. A very small amount of acetylcholine, nitroprusside and insulin will be applied to the skin of the forearm, to stimulate the bloodflow during LASCA. After 3 months of use of Empagliflozin the LASCA measurement will be repeated. Furthermore, at each visit 4 tubes of blood will be drawn for biobanking, and patients will be asked to fill out a quality of life questionnaire. During the trial, patients will be monitored in routine clinical care as indicated by their treating physician.
| Arm | Type | Receives |
|---|---|---|
| heart failure with preserved ejection fraction | Experimental | Drug: Participants receive 10mg Empaglifozin once daily on prescription from their treating physician. This is not an intervention in this trial, but part of their normal HFpEF treatmentEmpagliflozin 10mg, tablet, once daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- HFpEF diagnosis according to the ESC 2021 Guidelines for the diagnosis and treatment of acute and chronic heart failure Symptoms and signs of HF LVEF ≥ 50% (on any imaging modality) Objective evidence of cardiac structural and/or functional abnormalities consistent with the presence of LV diastolic dysfunction/ raised LV filling pressures, including raised natriuretic peptides (table 1) OR invasively measured pulmonary capillary wedge pressure (PCWP) of >15 mmHg (at rest) or ≥25 mmHg (with exercise) or left ventricular end diastolic pressure ≥ 16 mmhg (at rest).
- Ability to understand and speak the Dutch language
- Treatment with empagliflozin 10mg once daily is planned to be started by the treating physician
- Signed informed consent
Key exclusion criteria (9 listed)
- Unable or unwilling to sign informed consent
- Under 18 years of age
- Contra-indication to the use of empagliflozin Severe kidney disease (Glomerular filtration rate< 20 ml/min) Severe liver insufficiency Recent (<12 months) or planned major surgery (Including coronary artery bypass grafting, cardiac valve replacement) Severe acute disease (< 12 months) (Including acute coronary syndrome, TIA/CVA) Pregnancy
- Use of empagliflozin or other SGLT-2 inhibitor at baseline
- Known hypersensitivity to empagliflozin, acetylcholine, sodium nitroprusside or insulin
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 |
|---|---|---|
| Participants receive 10mg Empaglifozin once daily on prescription from their treating physician. This is not an intervention in this trial, but part of their normal HFpEF treatmentAlso: JardianceThe investigational medicinal product investigated in this trial (empagliflozin) is authorised for use in the European Union by the European Medicines Agency and will be used in accordance with the terms of the marketing authorization. The treating physician (cardiologist) will determine the indication for empagliflozin use, discuss the benefits and risks with the patient, prescribe the drug, and provide follow up after starting the drug, according to normal clinical practice. The study participants are not assigned to a particular therapeutic strategy decided by the clinical trial protocol. | Drug | heart failure with preserved ejection fraction |
Primary outcome
Cutaneous vascular conductance (CVC)
Time frame: Change from baseline to 3 months
Skin blood flow (arbitrary perfusion units, APU) is divided by the mean arterial pressure to yield the CVC.
4 secondary outcomes
baseline bloodflow and area under the curve
Time frame: Change from baseline to after 3 months
Serum ketone levels in mmol/L
Time frame: Change from baseline to after 3 months
EQ5D-5L questionnaire score
Time frame: Change from baseline to 3 months
EQ5D-5L questionnaire score
Time frame: Change from baseline to 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2023.
- Derived from this study: PubMed 40281528Mourmans SGJ, Achten A, Hermans R, Scheepers MJE, D'Alessandro E, Swennen G, Woudstra J, Appelman Y, Goor HV, Schalkwijk C, Knackstedt C, Weerts J, Eringa EC, van Empel VPM. The effect of empagliflozin on peripheral microvascular dysfunction in patients with heart failure with preserved ejection fraction. Cardiovasc Diabetol. 2025 Apr 25;24(1):182. doi: 10.1186/s12933-025-02679-8.
- Individual participant dataSharing planned: Undecided
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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.
Vanessa PM van Empel, Dr. contact
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 Participants receive 10mg Empaglifozin once daily on prescription from their treating physician. This is not an intervention in this trial, but part of their normal HFpEF treatment in people with Heart Failure With Preserved Ejection Fraction and Microvascular Dysfunction, run by Maastricht University Medical Center at 1 site in Netherlands.
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 9 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 21 Sep 2023. 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 Netherlands. 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?
Contact Sanne GJ Mourmans, Drs. (+31433871612, sanne.mourmans@mumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cutaneous vascular conductance (CVC) (time frame: Change from baseline to 3 months). 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 NCT06046612, 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 21 Sep 2023.