Empagliflozin for Pulmonary Arterial Hypertension

(EmPATH Trial)

Enrolling by invitation at 2 trial locations

Overseen By Erica Corrao, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Gustavo A Heresi, MD, MS

Must be taking: PAH-targeted therapy

Must not be taking: Insulin, SGLT2 inhibitors

Disqualifiers: Type 1 diabetes, Renal failure, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called empagliflozin to determine its effectiveness for people with pulmonary arterial hypertension (PAH), a condition characterized by narrowed blood vessels in the lungs. Participants will receive either the drug or a placebo (a pill with no active ingredients) to compare effects. The trial includes individuals diagnosed with PAH who are already on stable PAH medication. It aims to explore whether empagliflozin can effectively manage PAH symptoms. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to potential advancements in PAH management.

Will I have to stop taking my current medications?

You can continue taking your current PAH-targeted medications as long as they have been stable for at least 4 weeks before the screening. However, you cannot participate if you are currently using insulin, certain diabetes medications, or an SGLT2 inhibitor.

Is there any evidence suggesting that empagliflozin is likely to be safe for humans?

Research has shown that empagliflozin is generally safe and well-tolerated. Studies have found that this medication can help with conditions like pulmonary hypertension, a type of high blood pressure affecting the lungs and the right side of the heart.

This treatment has reduced hospital visits and improved heart function in some cases. Importantly, the FDA has already approved empagliflozin for treating diabetes, indicating it has passed significant safety checks for another condition.

Some side effects, such as urinary tract infections and increased urination, have been reported, but these are common for this type of medication. It is important to consult a doctor about any concerns and to determine if joining a trial is a suitable option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pulmonary arterial hypertension?

Empagliflozin is unique because it targets pulmonary arterial hypertension (PAH) by inhibiting a protein called SGLT2, which is primarily known for its role in glucose regulation. Unlike traditional PAH treatments that often focus on relaxing blood vessels or reducing inflammation, empagliflozin offers a novel mechanism that could improve heart and lung function by promoting diuresis and reducing blood volume. This dual benefit of cardiovascular and metabolic effects has researchers excited about its potential to address PAH in a new and potentially more effective way.

What evidence suggests that empagliflozin might be an effective treatment for pulmonary arterial hypertension?

Research has shown that empagliflozin can lower pressure in the blood vessels of the lungs, which is crucial for individuals with pulmonary arterial hypertension (PAH). One study demonstrated that this pressure reduction began as early as the first week of treatment. Another study found that empagliflozin improved the function of the right side of the heart, which is vital for heart health in PAH patients. Additionally, researchers observed that empagliflozin slowed the growth of certain cells that can worsen PAH. These findings suggest that empagliflozin may effectively treat PAH by managing both lung blood pressure and heart function. Participants in this trial will receive either empagliflozin or a placebo to further evaluate its effectiveness. ^{1 2 3 4 6}

Who Is on the Research Team?

Gustavo Heresi, MD

Principal Investigator

The Cleveland Clinic

Are You a Good Fit for This Trial?

This trial is for individuals with Pulmonary Arterial Hypertension (PAH) who are already on stable PAH-targeted medications. The specific eligibility criteria to join the study have not been provided, but typically include factors like age range, disease severity, and absence of certain health conditions.

Inclusion Criteria

PAH confirmed by right heart catheterization in the last 5 years

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

RV dysfunction defined FAC < 34.0% on echocardiography performed during the screening visit

Exclusion Criteria

Decompensated right heart failure, as adjudicated by the site PI

I have not taken SGLT2 inhibitors in the last 3 months.

I have a history of diabetic ketoacidosis or type 1 diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either empagliflozin 10 mg or placebo orally once daily

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Empagliflozin

Trial Overview The trial is testing Empagliflozin, a medication that could potentially improve heart function in PAH patients. Participants will be randomly assigned to either receive Empagliflozin or a placebo without knowing which one they're getting (triple-masked). They'll continue their current PAH treatments during the trial.

How Is the Trial Designed?

Group I: Empagliflozin Active Control 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Gustavo A Heresi, MD, MS

Lead Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

The Cleveland Clinic

Collaborator

Trials

1,072

Recruited

1,377,000+

Citations

1. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.052503

Empagliflozin Effects on Pulmonary Artery Pressure in ... Empagliflozin significantly reduced PADP, with effects that began at week 1 and amplified over time; average PADP (weeks 8–12) was 1.5 mm Hg ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12206267/

Effects of sodium-glucose cotransport-2 inhibitors treatment ... The EMBRACE-HF trial showed that empagliflozin reduced pulmonary arterial pressure in patients with left heart disease. ... In another placebo- ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06992440

NCT06992440 | Empagliflozin to Improve Right Ventricular ... The central hypothesis is that treatment with empagliflozin will improve right ventricular (RV) function and other key outcomes in patients with PAH.

4. pubs.acs.org pubs.acs.org/doi/10.1021/acsptsci.4c00127

Empagliflozin Attenuates Pulmonary Arterial Remodeling ... Empa inhibited significantly the proliferation of IPAH PASMCs but not of non-PAH PASMCs as evidenced by Ki67 immunofluorescence staining (Figure ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006291X20300346

The SGLT2 inhibitor empagliflozin reduces mortality and ... Hemodynamic assessments showed that empagliflozin treatment significantly reduced mean pulmonary artery pressure, right ventricular systolic pressure, and ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06554301/a-study-on-the-efficacy-and-safety-of-empagliflozin-in-the-treatment-of-pulmonary-arterial-hypertension

A Study on the Efficacy and Safety of Empagliflozin in ... The goal of this clinical trial is to learn if empagliflozin works to treat patients with pulmonary arterial hypertension.