Proof-of-concept study of Empagliflozin in patients with pulmonary arterial hypertension (EmPAH)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Philipps-Universitaet Marburg

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

3 Dec 2025 → ongoing

Decision date (initial)

2025-08-18

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Deutsches Zentrum für Lungenforschung

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

The primary endpoint of the study is to evaluate right ventricular diastolic function and its potential improvement following short-term treatment with Empagliflozin in PAH patients from baseline to end of treatment.

Secondary objectives 5

1. Evaluations of right ventricular function
2. Assessment of lung function
3. Disease severity
4. Patient quality of life
5. Safety

Conditions and MedDRA coding

Pulmonary arterial hypertension

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Male and female ≥18 years
2. Body Mass Index (BMI) >18kg/m2
3. Symptomatic PAH belonging to one of the following 2018 WHO Clinical Group 1 subtypes: a. Idiopathic PAH b. Heritable PAH c. Drug- or toxin-induced d. PAH associated with: 1. Connective tissue disease 2. Congenital systemic to pulmonary shunt (atrial septal defect, ventricular septal defect, patent ductus arteriosus) repaired at least one year prior to Screening 3. Human immunodeficiency virus (HIV) infection - if diagnosed with HIV, must have stable disease status defined as follows: a. stable treatment with HIV medications for at least 8 weeks prior to screening b. no active opportunistic infection during the screening period c. no hospitalizations due to HIV for at least 4 weeks prior to screening
4. WHO FC II or III
5. Confirmed diagnosis of PAH and meeting all the following hemodynamic criteria by means of a screening RHC completed prior to randomization: a. mPAP of >20 mmHg b. PVR ≥ 240 dyne•sec/cm5 c. Pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg
6. Currently on a stable treatment regimen with one or more treatments approved for PAH. Stable therapy is defined as receiving the same medication(s) for ≥ 12 weeks prior to the screening RHC and at a stable dose level for each for ≥ 8 weeks prior to the screening RHC.
7. For women of childbearing potential: a negative result in a pregnancy test AND agreement to practice a highly effective method of contraception* during the entire period from informed consent up to 30 days after the last administration of the IMP.
8. Written informed consent

Exclusion criteria 7

1. Major change in diuretic management during 48 hours prior to screening visit or 48 hours prior to randomization visit (major change defined by doubling of diuretic dose or addition of another diuretic medications).
2. Type 1 Diabetes
3. Pregnant or breastfeeding women
4. Following WHO PH Groups: · WHO PH Group 1 PAH associated with portal hypertension or schistosomiasis; · PH due to left heart disease (WHO PH Group 2); · lung diseases and/or hypoxia (WHO PH Group 3); · chronic thromboembolic PH (WHO PH Group 4); or · PH with unclear multifactorial mechanisms (WHO PH Group 5)
5. PH associated with: · significant venous or capillary involvement (PCWP > 15 mmHg); · pulmonary capillary hemangiomatosis; · portal hypertension; or · unrepaired congenital heart defects
6. Hypersensitivity to the active substance or other ingredients like: hydroxypropyl methylcellulose (HPMC), mannitol, colloidal silicon dioxide (highly dispersed)
7. Lithium therapy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Difference in the S´/RAAi ratio (measured by echocardiography) from baseline to week 4.

Secondary endpoints 5

1. • Echocardiography (RA Area, TAPSE/PASP, pericardial effusion, S´/RAAi) • cMRI (RV EF, SVI, RVESVI, PA flow for impedance calculation, RV and LV EDV, RV and LV ESV, RV and LS SV, RV and LV EF, RV and LV CO, RV and LV CO, RV and LV Myocardial Mass, LVEDVI, LVESVI, LVMI, RV and LV GLS, RV and LV T1, RV and LV T2, RV and LV GLE, PA Flow and Aortic Flow) • pulmonary hemodynamics via Swan-Ganz catheterization (mPAP, dPAP, sPAP, PAWP, cardiac output by Fick (direct or indirect), PVR, SvO2, CVP/RAP, Ca
2. • body plethysmography • FEV1, FEV1%pred, FVC, FVCpred, TLC%pred, DLCO%pred, FVC obs.v., FEV1 obs.v., TLC obs. V., TLC%pred, RV obs. V., VC obs. V., DLCO, sRaw effektiv, • Blood gas analysis: Capillary pO2, Capillary pCO2
3. • Six minutes walking distance (6MWD) • BNP • CPET (VO2 and VE/VCO2 slope, as well as WHO FC)
4. • Patient-reported outcome measures (PAH-Sympact, MLC questionnaire, EQ-5D-5L Mobility Score)
5. • Adverse event (AE), Serious (S) AE assessment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Philipps-Universitaet Marburg

Sponsor organisation

Philipps-Universitaet Marburg

Address

Karl-Von-Frisch-Strasse 4

City

Marburg

Postcode

35043

Country

Germany

Scientific contact point

Organisation

Philipps-Universitaet Marburg

Contact name

EmPAH Study team

Public contact point

Organisation

Philipps-Universitaet Marburg

Contact name

EmPAH study team

Third parties 1

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications