Pulmonary Arterial HypertensionPhase 2EmPATHNCT06992440
Empagliflozin to Improve Right Ventricular Function in Pulmonary Arterial Hypertension
A Phase 2 study testing Empagliflozin 10 MG in people with Pulmonary Arterial Hypertension, run by Gustavo A Heresi, MD, MS at 3 sites in United States.
Trial summary
Randomized, triple-masked, parallel arm clinical trial of empagliflozin versus placebo in pulmonary arterial hypertension (PAH) participants on stable approved PAH-targeted medical therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Empagliflozin 10 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 78 participants
- Where
- 3 sitesUnited States
- Study dates
- 26 Jun 2025to Sep 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- In order to be eligible to participate in this study, an individual must meet all the following criteria:
- Provision of signed and dated informed consent form
- Ability and stated willingness to comply with all study procedures and availability for the duration of the study
- Ability to read and write in English
- Male or female, aged 18 years or older, with group 1 PAH, idiopathic, heritable, associated with drugs and toxins, associated with connective tissue disease and with congenital heart disease (simple repaired or unrepaired defects) according to the current guidelines and adjudicated by the local PI
- PAH confirmed by right heart catheterization in the last 5 years
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- RV dysfunction defined as FAC ≤ 40.0% on echocardiography performed during the screening visit. In PVDOMICS, FAC has a strong correlation with CMR RV ejection fraction; group 1 PAH patients with an FAC ≤ 40% (mean 27.0 ± 8.0%) had a mean RV ejection fraction of 35.5 ± 11.3% CMR RV ejection fraction ≤ 54% classifies PAH as intermediate (37-54%) or high (<37%) risk under current guidelines. However, to ensure we recruit patients with significantly impaired RV function, patients with RV FAC between 35.0-40.0% on the screening echocardiogram will have to meet at least one of the following additional criteria: a) TAPSE/sPAP ratio < 0.31 mm/mmHg; b) elevated right atrial pressure defined as inferior vena cava (IVC) > 2.1 cm in diameter and the IVC does not collapse with sniff/respiration; c) RV enlargement defined as RV basal diameter ≥ 4.1 cm; d) RV free wall longitudinal strain ≥ -22%; e) Interventricular septal flattening; and f) RV outflow tract mid or late systolic notching.
- On FDA-approved PAH-targeted therapy (any combination including infused prostacyclin analogues and sotatercept) with stable doses for at least 8 weeks or 24 weeks for sotatercept prior to the screening visit and no clinical plans to change this therapy.
- Diuretic doses stable for at least 4 weeks prior to screening. After screening, diuretic doses may be changed as directed by the site PIs and/or the treating physician.
- Ability to take oral medication and willingness to adhere to the study drug regimen.
- For females of reproductive potential: use of highly effective contraception for at least 4 weeks prior to screening and agreement to use such a method during study participation and for an additional 2 weeks after the end of study drug administration
- Able to have baseline and week 24 CMR according to Imaging Core criteria, as adjudicated by the Site PI
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Current use of insulin, insulin secretagogues (sulfonylureas and meglitinides), lithium or an SGLT2 inhibitor
- Use of an SGLT2 inhibitor within the past 3 months prior to screening
- Prior documented inability to tolerate an SGLT2 inhibitor
- Volume depletion, as ascertained by the site PI, at screening or baseline
- History of diabetic ketoacidosis or type 1 diabetes mellitus
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- Chronic alcohol or drug abuse
- More than one bacterial or yeast genitourinary tract infection in the year prior to enrollment
- Estimated glomerular filtration rate under 30 mL/minute/1.73m2 or on renal replacement therapy
- Pregnancy or lactation
- Known allergy or hypersensitivity to empagliflozin or another SGLT-2 inhibitor
- Currently taking or has taken another investigational drug within the past 4 weeks
- Enrollment in another randomized intervention trial. (Participants participating in observational trials will not be excluded).
- Decompensated right heart failure, as adjudicated by the site PI.
- Screening HbA1c >10% with symptoms such as polyuria and polydipsia
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
The Johns Hopkins Hospital
Baltimore, Maryland, 21287
Stephen Mathai, MD, smathai4@jhmi.edu
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
Gustavo Heresi, MD, heresig@ccf.org
- Recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Anna Hemnes, MD, anna.r.hemnes@vumc.org
About this study
Randomized, triple-masked, parallel arm clinical trial of empagliflozin versus placebo in pulmonary arterial hypertension (PAH) participants on stable approved PAH-targeted medical therapy.
Read the detailed description
The central hypothesis is that treatment with empagliflozin will improve right ventricular (RV) function and other key outcomes in patients with PAH. To test this hypothesis, the EmPATH team will conduct a multicenter Phase 2 clinical trial of empagliflozin to improve right ventricular (RV) function in pulmonary arterial hypertension (PAH). Participants will be randomized in a 1:1 ratio into two arms: empagliflozin 10 mg or matching placebo orally daily for 6 months. Randomization will be stratified by enrollment site and blocked with randomly varying block sizes. The analysis plan includes no formal interim analysis of treatment efficacy or futility.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- Empagliflozin 10 MG, Placebo
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin 10 MGDrug
Also called Jardiance
10 mg tablet once daily
PlaceboDrug
matching tablet once daily
| Study group | Role | What they receive |
|---|---|---|
| Empagliflozin | Active comparator | Participants receive Empagliflozin 10 mg orally once daily for 24 weeks. Empagliflozin is over-encapsulated to match placebo. Receives: Drug: Empagliflozin 10 MG |
| Placebo | Placebo comparator | Participants receive placebo tablet over-encapsulated to match Empagliflozin orally once daily for 24 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in RV ejection fraction measured by CMR
RV ejection fraction measured by CMR before and after treatment
Measured: 24 weeks
Secondary outcomes (8)
Change in Fractional Area Change (FAC) measured by echocardiography
Fractional Area Change (FAC) measured by echocardiography before and after treatment
Measured: 24 weeks
Change in the 6-minute walk distance (6MWD)
6-minute walk distance (6MWD) before and after treatment
Measured: 24 weeks
Change in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels
NT-proBNP before and after treatment
Measured: 24 weeks
Time to clinical worsening
Composite endpoint defined as the occurrence of death, listing for lung or heart-lung transplantation, initiation of an additional PAH-targeted medication or increase in the prostacyclin dose by ≥10% due to PAH clinical worsening judged by the treating PAH clinician, atrial septostomy, hospitalization ≥ 24 hours for worsening of PAH, or functional deterioration defined by both a worsened NYHA functional class and a decrease in 6-minute walk distance by ≥15% from baseline.
Measured: 24 weeks
Change in Multicomponent improvement
Percentage of participants meeting all three of the following criteria at the end of the study: any improvement in NYHA class or maintenance of class I-II, increase in 6-minute walk distance by at least 30 meters, decrease in NT-proBNP by at least 30%.
Measured: 24 weeks
Change in French risk score
Proportion of participants meeting all three low-risk criteria at the end of the study: NYHA class I or II, 6-minute walk distance > 440 meters, and NT-proBNP < 300 pg/ml at Week 24 versus baseline.
Measured: 24 weeks
Change in health-related quality of life (HRQOL)
Change in health-related quality of life (HRQOL) using participant reported outcome:
the Medical Outcomes Survey Short Form-36 (SF-36) instrument Physical Health Composite (PHC) score.
Measured: 24 weeks
Change in health-related quality of life (HRQOL)
Change in health-related quality of life (HRQOL)using participant reported outcome: the PAH-specific emPHasis-10 questionnaire.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2025
- Study start26 Jun 2025
- Primary completionJul 2030 (estimated)
- Study completionSep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial HypertensionStudies 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 78 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Gustavo A Heresi, MD, MS
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Gustavo A Heresi, MD, MS, The Cleveland Clinic
- Investigators
- Gustavo Heresi, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06992440
- Sponsor's protocol ID
- 25-168
- Other IDs
- UG3HL175041, UH3HL175041
- Acronym
- EmPATH
- Status last verified
- Jul 2026
- First submitted
- 13 May 2025
- Last updated
- 13 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: After the study is completed, the de-identified, archived data will be transmitted to and stored at the NHLBI BioData Catalyst (BDC) or to the data repository designated by the NHLBI when the study ends. Data and samples could be used in research. Blood samples will be stored in the EmPATH biorepository for future studies. Some of this research might take place before the EmPATH Trial close out. The research will be approved by the Steering Committee (which includes the NHLBI). At a date agreed upon with the NIH BioLINCC, the EmPATH residual blood samples accepted for storage will be shipped to BioLINCC. After the EmPATH Trial ends, members of the PAH community including members of the EmPATH Steering Committee members may request biological samples from BioLINCC.
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Empagliflozin to Improve Right Ventricular Function in Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT06992440
- Acronym / sponsor ID
- EmPATH / 25-168
- Conditions
- Pulmonary Arterial Hypertension
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 78 participants (estimated)
- Lead sponsor
- Gustavo A Heresi, MD, MSUniversity, hospital or other
- Collaborators
- The Cleveland Clinic, National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 26 Jun 2025 (actual)
- Primary completion
- Jul 2030 (estimated)
- Study completion
- Sep 2030 (estimated)
- First posted
- 28 May 2025 (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.
Randomized, triple-masked, parallel arm clinical trial of empagliflozin versus placebo in pulmonary arterial hypertension (PAH) participants on stable approved PAH-targeted medical therapy.
Detailed description
The central hypothesis is that treatment with empagliflozin will improve right ventricular (RV) function and other key outcomes in patients with PAH. To test this hypothesis, the EmPATH team will conduct a multicenter Phase 2 clinical trial of empagliflozin to improve right ventricular (RV) function in pulmonary arterial hypertension (PAH). Participants will be randomized in a 1:1 ratio into two arms: empagliflozin 10 mg or matching placebo orally daily for 6 months. Randomization will be stratified by enrollment site and blocked with randomly varying block sizes. The analysis plan includes no formal interim analysis of treatment efficacy or futility.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Empagliflozin | Active comparator | Drug: Empagliflozin 10 MGParticipants receive Empagliflozin 10 mg orally once daily for 24 weeks. Empagliflozin is over-encapsulated to match placebo. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants receive placebo tablet over-encapsulated to match Empagliflozin orally once daily for 24 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- In order to be eligible to participate in this study, an individual must meet all the following criteria:
Key exclusion criteria (15 listed)
- An individual who meets any of the following criteria will be excluded from participation in this 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: Jardiance10 mg tablet once daily | Drug | Empagliflozin |
| Placebomatching tablet once daily | Drug | Placebo |
Primary outcome
Change in RV ejection fraction measured by CMR
Time frame: 24 weeks
RV ejection fraction measured by CMR before and after treatment
8 secondary outcomes
Change in Fractional Area Change (FAC) measured by echocardiography
Time frame: 24 weeks
Change in the 6-minute walk distance (6MWD)
Time frame: 24 weeks
Change in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels
Time frame: 24 weeks
Time to clinical worsening
Time frame: 24 weeks
Change in Multicomponent improvement
Time frame: 24 weeks
Change in French risk score
Time frame: 24 weeks
Change in health-related quality of life (HRQOL)
Time frame: 24 weeks
Change in health-related quality of life (HRQOL)
Time frame: 24 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2026.
- Individual participant dataSharing planned: Yes. After the study is completed, the de-identified, archived data will be transmitted to and stored at the NHLBI BioData Catalyst (BDC) or to the data repository designated by the NHLBI when the study ends. Data and samples could be used in research. Blood samples will be stored in the EmPATH biorepository for future studies. Some of this research might take place before the EmPATH Trial close out. The research will be approved by the Steering Committee (which includes the NHLBI). At a date agreed upon with the NIH BioLINCC, the EmPATH residual blood samples accepted for storage will be shipped to BioLINCC. After the EmPATH Trial ends, members of the PAH community including members of the EmPATH Steering Committee members may request biological samples from BioLINCC.
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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.
Gustavo Heresi, MD principal investigator
The Cleveland Clinic
3 sites 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 10 MG in people with Pulmonary Arterial Hypertension, run by Gustavo A Heresi, MD, MS at 3 sites in United States.
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 12 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 13 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Gustavo Heresi, MD (216 636-5327, HERESIG@ccf.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in RV ejection fraction measured by CMR (time frame: 24 weeks). 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 13 Aug 2026.