ENROLLING_BY_INVITATION

Empagliflozin to Improve Right Ventricular Function in Pulmonary Arterial Hypertension

Conditions

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Randomized, triple-masked, parallel arm clinical trial of empagliflozin versus placebo in pulmonary arterial hypertension (PAH) participants on stable approved PAH-targeted medical therapy.

Official Title

Empagliflozin to Improve Right Ventricular Function in Pulmonary Arterial Hypertension

Quick Facts

Study Start:2025-06-26

Study Completion:2030-09

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ENROLLING_BY_INVITATION

Study ID

NCT06992440

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 4 weeks 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	* 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

Inclusion Criteria

Exclusion 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 4 weeks 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

* 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

Contacts and Locations

Principal Investigator

Gustavo Heresi, MD

PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Study Locations (Sites)

The Johns Hopkins Hospital

Baltimore, Maryland, 21287

United States

Cleveland Clinic

Cleveland, Ohio, 44195

United States

Vanderbilt University Medical Center

Nashville, Tennessee, 37232

United States

Collaborators and Investigators

Sponsor: Gustavo A Heresi, MD, MS

Gustavo Heresi, MD, PRINCIPAL_INVESTIGATOR, The Cleveland Clinic

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-06-26

Study Completion Date2030-09

Study Record Updates

Study Start Date2025-06-26

Study Completion Date2030-09

Terms related to this study

Additional Relevant MeSH Terms

Pulmonary Arterial Hypertension