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 (ARTISAN)

A Phase 4, Prospective, Multicenter, Single-Arm Study of a Mean Pulmonary Artery Pressure-Targeted Approach With Early and Rapid Treprostinil Therapy to Reverse Right Ventricular Remodeling in Patients With Pulmonary Arterial Hypertension: ARTISAN (Afterload Reduction To Improve Right Ventricular Structure And FuNction)

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Parenteral Treprostinil; Drug: Oral Treprostinil

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85020
      • HonorHealth John C. Lincoln Medical Center
    • Phoenix, Arizona, United States, 85006
      • Banner University Medical Center (University of Arizona)
  • California
    • Fresno, California, United States, 93701
      • University of California San Francisco - Fresno
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
    • San Francisco, California, United States, 94143
      • University of California San Francisco Pulmonary, Critical Care, Allergy and Sleep Medicine
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Hartford Hospital
  • Florida
    • Tampa, Florida, United States, 33606
      • USF
  • Georgia
    • Austell, Georgia, United States, 30106
      • Georgia Clinical Research
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46219
      • Community Health Network
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health North Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
  • New York
    • Rochester, New York, United States, 14623
      • University of Rochester Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • INTEGRIS Baptist Medical Center
    • Tulsa, Oklahoma, United States, 74104
      • Oklahoma Heart Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Greenville, South Carolina, United States, 29605
      • Prisma Health
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • Carilion Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Exclusion Criteria:

• 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

CardioMEMS-related Exclusion Criteria, if applicable:

• 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

NOTE: Other inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treprostinil; 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; Parenteral treprostinil will be administered per schedule specified in the arm description.; Other Names: Remodulin; Drug: Oral Treprostinil; Oral treprostinil will be administered per schedule specified in the arm description.; Other Names: Orenitram

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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).	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
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

Collaborators and Investigators

• Sponsor: United Therapeutics
• Collaborators: Lung Biotechnology PBC

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2022
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: January 10, 2022
• First Submitted That Met QC Criteria: January 10, 2022
• First Posted (Actual): January 24, 2022

Study Record Updates

• Last Update Posted (Estimated): December 9, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Antihypertensive Agents; treprostinil
• Other Study ID Numbers: REM-PH-418

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No