Randomized, triple-masked, parallel arm clinical trial of empagliflozin versus placebo in pulmonary arterial hypertension (PAH) participants on stable approved PAH-targeted medical therapy.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
78
10 mg tablet once daily
matching tablet once daily
The Johns Hopkins Hospital
Baltimore, Maryland, United States
RECRUITINGCleveland Clinic
Cleveland, Ohio, United States
RECRUITINGVanderbilt University Medical Center
Nashville, Tennessee, United States
RECRUITINGChange in RV ejection fraction measured by CMR
RV ejection fraction measured by CMR before and after treatment
Time frame: 24 weeks
Change in Fractional Area Change (FAC) measured by echocardiography
Fractional Area Change (FAC) measured by echocardiography before and after treatment
Time frame: 24 weeks
Change in the 6-minute walk distance (6MWD)
6-minute walk distance (6MWD) before and after treatment
Time frame: 24 weeks
Change in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels
NT-proBNP before and after treatment
Time frame: 24 weeks
Time to clinical worsening
Composite endpoint defined as the occurrence of death, listing for lung or heart-lung transplantation, initiation of an additional PAH-targeted medication or increase in the prostacyclin dose by ≥10% due to PAH clinical worsening judged by the treating PAH clinician, atrial septostomy, hospitalization ≥ 24 hours for worsening of PAH, or functional deterioration defined by both a worsened NYHA functional class and a decrease in 6-minute walk distance by ≥15% from baseline.
Time frame: 24 weeks
Change in Multicomponent improvement
Percentage of participants meeting all three of the following criteria at the end of the study: any improvement in NYHA class or maintenance of class I-II, increase in 6-minute walk distance by at least 30 meters, decrease in NT-proBNP by at least 30%.
Time frame: 24 weeks
Change in French risk score
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Proportion of participants meeting all three low-risk criteria at the end of the study: NYHA class I or II, 6-minute walk distance \> 440 meters, and NT-proBNP \< 300 pg/ml at Week 24 versus baseline.
Time frame: 24 weeks
Change in health-related quality of life (HRQOL)
Change in health-related quality of life (HRQOL) using participant reported outcome: the Medical Outcomes Survey Short Form-36 (SF-36) instrument Physical Health Composite (PHC) score.
Time frame: 24 weeks
Change in health-related quality of life (HRQOL)
Change in health-related quality of life (HRQOL)using participant reported outcome: the PAH-specific emPHasis-10 questionnaire.
Time frame: 24 weeks