A Study of a Mean Pulmonary Artery Pressure-Targeted Approach With Early and Rapid Treprostinil Therapy to Reverse Right Ventricular Remodeling in Participants With Pulmonary Arterial Hypertension

NCT05203510 | Active Not Recruiting Phase 4 FDA Drug

• 1 other identifier: REM-PH-418
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 28

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).

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Right Ventricular Ejection Fraction (RVEF), as Measured by Cardiac Magnetic Resonance Imaging (cMRI) at Month 12

  Baseline, Month 12

Secondary Outcomes (13)

• 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

• 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

Study Arms (1)

Treprostinil

EXPERIMENTAL

Participants will receive parenteral treprostinil at initial dose of 1.25 nanograms/kilogram/minute (at minimum) either intravenously or subcutaneously. Based on mPAP assessments and after a minimum dose of parenteral treprostinil is reached, at Investigator's (PI's) discretion, participants may transition to oral treprostinil and continue dose uptitration for further reduction of mPAP. Based on Month 12 mPAP assessment, participants may transition from parenteral to oral treprostinil at PI's discretion after completion of Month 12 assessment and continue uptitration for further reduction of mPAP. If minimum dose of parenteral treprostinil is not reached at Month 6/12 at PI's discretion, uptitration of parenteral treprostinil or oral treprostinil transition may occur to maintain normal mPAP. Treprostinil therapy (parenteral or oral) may continue as tolerated toward goal of further reduction of mPAP until Month 36.

Drug: Parenteral Treprostinil; Drug: Oral Treprostinil

Interventions

Parenteral Treprostinil DRUG

Parenteral treprostinil will be administered per schedule specified in the arm description.

Also known as: Remodulin

Treprostinil

Oral Treprostinil DRUG

Oral treprostinil will be administered per schedule specified in the arm description.

Also known as: Orenitram

Treprostinil

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• MWD \>165 meters

You may not qualify if:

• Prior or current use of epoprostenol, treprostinil, iloprost, beraprost, or selexipag
• Positive vasoreactivity test in idiopathic, heritable, or drug/toxin induced PAH
• Amphetamine use within the past 12 months
• WHO Groups 2, 3, 4, and 5
• Use of any other investigational drug, device, or therapy within 30 days of the Baseline visit
• Moderate or severe hepatic impairment (Child-Pugh Class B and C)
• Any other clinically significant illness or abnormal laboratory value(s) measured during screening that, in the opinion of the Investigator, might adversely affect interpretation of the study data or participant safety (for example, active infection, chronic thromboembolic pulmonary hypertension, or acute/recent deep vein thrombosis or pulmonary embolism)
• Chronic atrial fibrillation, multiple premature ventricular or atrial contractions of clinical significance, or any other condition that would interfere with proper cardiac gating during cMRI
• Permanent cardiac pacemaker or automatic internal cardioverter that would interfere with conduct of cMRI
• Metallic implant (for example, defibrillator, neurostimulator, hearing aid, permanent infusion device, implantable pump, or body plates/screws/bolts) that would interfere with conduct of cMRI
• Previously implanted with CardioMEMS pulmonary artery Sensor or unwilling/unable to permit collection and perform upload (transmission) of pulmonary artery pressure (PAP) readings
• Unable to take dual antiplatelet or anticoagulation therapy for 30 days after CardioMEMS PA Sensor implantation unless the participant has an indication for warfarin or direct oral anticoagulant

Sponsors & Collaborators

• United Therapeutics: lead
• Lung Biotechnology PBC: collaborator

Study Sites (28)

Banner University Medical Center (University of Arizona)

Phoenix, Arizona, 85006, United States

Location

HonorHealth John C. Lincoln Medical Center

Phoenix, Arizona, 85020, United States

Location

University of California San Francisco - Fresno

Fresno, California, 93701, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

University of California San Francisco Pulmonary, Critical Care, Allergy and Sleep Medicine

San Francisco, California, 94143, United States

Location

Hartford Hospital

Hartford, Connecticut, 06106, United States

Location

USF

Tampa, Florida, 33606, United States

Location

Georgia Clinical Research

Austell, Georgia, 30106, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Indiana University Health North Hospital

Indianapolis, Indiana, 46202, United States

Location

Community Health Network

Indianapolis, Indiana, 46219, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Morristown Medical Center

Morristown, New Jersey, 07960, United States

Location

University of Rochester Medical Center

Rochester, New York, 14623, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Integris Baptist Medical Center

Oklahoma City, Oklahoma, 73112, United States

Location

Oklahoma Heart Institute

Tulsa, Oklahoma, 74104, United States

Location

Temple Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Prisma Health

Greenville, South Carolina, 29605, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Carilion Clinic

Roanoke, Virginia, 24014, United States

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

treprostinil

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2022
• First Posted: January 24, 2022
• Study Start: October 20, 2022
• Primary Completion: April 30, 2026
• Study Completion (Estimated): April 30, 2028
• Last Updated: December 9, 2025

Record last verified: 2025-05

Locations

US (28)