Pulmonary Arterial Hypertension
Conditions
Brief summary
The primary objective of this study is to assess the effect of early and rapid treprostinil therapy for mean pulmonary artery pressure (mPAP) reduction to improve right ventricular (RV) function and reverse RV remodeling in participants with pulmonary arterial hypertension (PAH).
Interventions
DRUGParenteral Treprostinil
Parenteral treprostinil will be administered per schedule specified in the arm description.
Oral treprostinil will be administered per schedule specified in the arm description.
Sponsors
Lung Biotechnology PBC
United Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed PAH (WHO Group 1) classified by one of the following subgroups: * Idiopathic, heritable or drug/toxin induced (with the exception of amphetamine-induced PAH) * Associated with repaired congenital systemic-to-pulmonary shunts (repaired ≥1 year) * Associated with connective tissue disease * Associated with human immunodeficiency virus infection * Baseline visit right heart catheterization (RHC) must also meet the following criteria: * mPAP \>35 mmHg * Pulmonary vascular resistance (PVR) \>2 Wood units * Pulmonary artery wedge pressure (PAWP) ≤15 mmHg * On a stable dose of an endothelin receptor antagonist (ERA) and/or phosphodiesterase type 5 inhibitor (PDE-5i) or soluble guanylate cyclase stimulator (sGC) therapy or if treatment naïve, willing to take one of these medications in addition to study drug * REVEAL Lite 2 risk score ≤9 * WHO FC II or III * 6MWD \>165 meters
Exclusion criteria
PAH-related
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Right Ventricular Ejection Fraction (RVEF), as Measured by Cardiac Magnetic Resonance Imaging (cMRI) at Month 12 | Baseline, Month 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in mPAP at Month 12 | Baseline, Month 12 | — |
| Number of Participants With Clinical Improvement From Baseline to Month 12, 24, and 36 | Baseline to Months 12, 24, and 36 | Clinical improvement is defined as meeting all 3 criteria: - improvement in six-minute walk distance (6MWD) increase ≥10% or ≥30 meters; - improvement in World Health Organization (WHO) functional class (FC) or maintenance of WHO FC I/II; - improvement in N-terminal pro-brain natriuretic peptide (NT-proBNP) decrease ≥30% or \<300 ng/liter (L). |
| Change From Baseline in RV-Pulmonary Artery (PA) Coupling Estimated by the Ratio of Stroke Volume by End Systolic Volume at Month 12 | Baseline, Month 12 | — |
| Change From Baseline in RV End-Diastolic Volume Index at Month 12 | Baseline, Month 12 | — |
| Change From Baseline in RV Stroke Volume Index at Month 12 | Baseline, Month 12 | — |
| Change From Baseline in 6MWD at Month 12, 24, and 36 | Baseline, Months 12, 24, and 36 | — |
| Change From Baseline in Registry to EValuate EArly and Long-Term PAH Disease Management (REVEAL) Lite 2 Risk Score at Months 12, 24, and 36 | Baseline, Months 12, 24, and 36 | — |
| Change From Baseline in WHO FC at Months 12, 24, and 36 | Baseline, Months 12, 24, and 36 | — |
| Change From Baseline in NT-proBNP at Months 12, 24, and 36 | Baseline, Months 12, 24, and 36 | — |
| Change From Baseline in Borg Dyspnea Score at Months 12, 24, and 36 | Baseline, Months 12, 24, and 36 | — |
| Change From Baseline in RV-PA Coupling Estimated by the Ratio of Tricuspid Annular Plane Systolic Excursion by Pulmonary Artery Systolic Pressure (TAPSE/PASP) at Months 12, 24, and 36 | Baseline, Months 12, 24, and 36 | — |
| Survival Rate: Number of Participants who Survived at Months 12, 24, and 36 | Baseline to Months 12, 24, and 36 | — |
| Change From Baseline in mPAP at Months 24 and 36 | Baseline, Months 24 and 36 | — |
Countries
United States
Outcome results
None listed