Empagliflozin to Improve Right Ventricular Function in Pulmonary Arterial Hypertension

NCT06992440 | Enrolling By Invitation Phase 2 DMC FDA Drug

• 3 other identifiers: 25-168UG3HL175041UH3HL175041
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (1)

• Change in RV ejection fraction measured by CMR

  RV ejection fraction measured by CMR before and after treatment

  24 weeks

Secondary Outcomes (8)

• Change in Fractional Area Change (FAC) measured by echocardiography

  24 weeks

• Change in the 6-minute walk distance (6MWD)

  24 weeks

• Change in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels

  24 weeks

• Time to clinical worsening

  24 weeks

• Change in Multicomponent improvement

  24 weeks

Study Arms (2)

Empagliflozin

ACTIVE COMPARATOR

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

Drug: Empagliflozin 10 MG

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Empagliflozin 10 MG DRUG

10 mg tablet once daily

Also known as: Jardiance

Empagliflozin

Placebo DRUG

matching tablet once daily

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Gustavo A Heresi, MD, MS: lead
• The Cleveland Clinic: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (3)

The Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Gustavo Heresi, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 13, 2025
• First Posted: May 28, 2025
• Study Start: June 26, 2025
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): September 1, 2030
• Last Updated: December 17, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Available per NIH data management
• Access Criteria: Researchers can access NHLBI data and biospecimens through the BioLINCC website, requesting access to data and biospecimens in the Biorepository, and utilizing the BioData Catalyst ecosystem.

Locations

US (3)