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

Pulmonary Arterial Hypertension Clinical Trial

— ARTISAN  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05203510
• Other study ID #: REM-PH-418
• Status: Recruiting
• Phase: Phase 4
• Start date: August 10, 2022
• Est. completion date: September 12, 2024

Study information

• Verified date: February 2024
• Source: United Therapeutics
• Contact: Mary Lou Tomson
• Phone: 240-821-1881
• Email: artisan[@]lungbiotechnology.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: September 12, 2024
• Est. primary completion date: September 12, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension
• Ventricular Remodeling

Intervention

Drug:
• Parenteral Treprostinil
Parenteral treprostinil will be administered per schedule specified in the arm description.
• Oral Treprostinil
Oral treprostinil will be administered per schedule specified in the arm description.

Locations

Country	Name	City	State
United States	Georgia Clinical Research	Austell	Georgia
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	University of California San Francisco - Fresno	Fresno	California
United States	Prisma Health - Upstate	Greenville	South Carolina
United States	Hartford Hospital	Hartford	Connecticut
United States	Integris Baptist Medical Center	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Temple Hospital	Philadelphia	Pennsylvania
United States	Banner University Medical Center (University of Arizona)	Phoenix	Arizona
United States	HonorHealth John C. Lincoln Medical Center	Phoenix	Arizona
United States	Carilion Clinic	Roanoke	Virginia
United States	University of Rochester Medical Center	Rochester	New York
United States	University of California San Francisco Pulmonary, Critical Care, Allergy and Sleep Medicine	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
United Therapeutics	Lung Biotechnology PBC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Right Ventricular Ejection Fraction (RVEF), as Measured by Cardiac Magnetic Resonance Imaging (cMRI) at Month 12		Baseline, Month 12
Secondary	Change From Baseline in mPAP at Month 12		Baseline, Month 12
Secondary	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
Secondary	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
Secondary	Change From Baseline in RV End-Diastolic Volume Index at Month 12		Baseline, Month 12
Secondary	Change From Baseline in RV Stroke Volume Index at Month 12		Baseline, Month 12
Secondary	Change From Baseline in 6MWD at Month 12, 24, and 36		Baseline, Months 12, 24, and 36
Secondary	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
Secondary	Change From Baseline in WHO FC at Months 12, 24, and 36		Baseline, Months 12, 24, and 36
Secondary	Change From Baseline in NT-proBNP at Months 12, 24, and 36		Baseline, Months 12, 24, and 36
Secondary	Change From Baseline in Borg Dyspnea Score at Months 12, 24, and 36		Baseline, Months 12, 24, and 36
Secondary	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
Secondary	Survival Rate: Number of Participants who Survived at Months 12, 24, and 36		Baseline to Months 12, 24, and 36
Secondary	Change From Baseline in mPAP at Months 24 and 36		Baseline, Months 24 and 36