Empagliflozin to Improve Right Ventricular Function in Pulmonary Arterial Hypertension

NCT ID: NCT06992440

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ENROLLING_BY_INVITATION

Clinical Phase

PHASE2

Total Enrollment

78 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-06-26

Study Completion Date

2030-09-30

Brief Summary

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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

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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

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Pulmonary Arterial Hypertension

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Empagliflozin

Participants receive Empagliflozin 10 mg orally once daily for 24 weeks. Empagliflozin is over-encapsulated to match placebo.

Group Type ACTIVE_COMPARATOR

Empagliflozin 10 MG

Intervention Type DRUG

10 mg tablet once daily

Placebo

Participants receive placebo tablet over-encapsulated to match Empagliflozin orally once daily for 24 weeks.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

matching tablet once daily

Interventions

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Empagliflozin 10 MG

10 mg tablet once daily

Intervention Type DRUG

Placebo

matching tablet once daily

Intervention Type DRUG

Other Intervention Names

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Jardiance

Eligibility Criteria

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Inclusion Criteria

* In order to be eligible to participate in this study, an individual must meet all the following criteria:

1. Provision of signed and dated informed consent form
2. Ability and stated willingness to comply with all study procedures and availability for the duration of the study
3. Ability to read and write in English
4. 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
5. PAH confirmed by right heart catheterization in the last 5 years
6. RV dysfunction defined FAC ≤ 34.0% on echocardiography performed during the screening visit. In PVDOMICS, FAC has a strong correlation with CMR RV ejection fraction, and FAC \< 34% predicts a CMR RV ejection fraction \<37% with a large c-statistic of 0.9. CMR RV ejection fraction \<37% is strongly associated with increased mortality and classifies PAH as high risk under the current guidelines. We do not expect this will curtail recruitment as the mean FAC in the PVDOMICS cohort is 30 ± 10%, a population like the one that will be enrolled in this study.
7. 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
8. 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.
9. Ability to take oral medication and willingness to adhere to the study drug regimen.
10. 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
11. Able to have baseline and week 24 CMR according to Imaging Core criteria, as adjudicated by the Site PI

Exclusion Criteria

* An individual who meets any of the following criteria will be excluded from participation in this study:

1. Current use of insulin, insulin secretagogues (sulfonylureas and meglitinides), lithium or an SGLT2 inhibitor
2. Use of an SGLT2 inhibitor within the past 3 months prior to screening
3. Prior documented inability to tolerate an SGLT2 inhibitor
4. Volume depletion, as ascertained by the site PI, at screening or baseline
5. History of diabetic ketoacidosis or type 1 diabetes mellitus
6. Chronic alcohol or drug abuse
7. More than one bacterial or yeast genitourinary tract infection in the year prior to enrollment
8. Estimated glomerular filtration rate under 30 mL/minute/1.73m2 or on renal replacement therapy
9. Pregnancy or lactation
10. Known allergy or hypersensitivity to empagliflozin or another SGLT-2 inhibitor
11. Currently taking or has taken another investigational drug within the past 4 weeks
12. Enrollment in another randomized intervention trial. (Participants participating in observational trials will not be excluded).
13. Decompensated right heart failure, as adjudicated by the site PI.
14. Screening HbA1c \>10% with symptoms such as polyuria and polydipsia
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Cleveland Clinic

OTHER

Sponsor Role collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Gustavo A Heresi, MD, MS

OTHER

Sponsor Role lead

Responsible Party

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Gustavo A Heresi, MD, MS

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Gustavo Heresi, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

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The Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Countries

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United States

Other Identifiers

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UG3HL175041

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UH3HL175041

Identifier Type: NIH

Identifier Source: secondary_id

View Link

25-168

Identifier Type: -

Identifier Source: org_study_id