Clinical trial NCT05203510: 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
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Pulmonary Arterial Hypertension
Lead sponsor: United Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Lung Biotechnology PBC
First posted: 2022-01-24
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Right Ventricular Ejection Fraction (RVEF), as Measured by Cardiac Magnetic Resonance Imaging (cMRI) at Month 12
timeFrame: Baseline, Month 12
Secondary outcomes:
measure: Change From Baseline in mPAP at Month 12
timeFrame: Baseline, Month 12
measure: Number of Participants With Clinical Improvement From Baseline to Month 12, 24, and 36
timeFrame: Baseline to Months 12, 24, and 36
measure: Change From Baseline in RV-Pulmonary Artery (PA) Coupling Estimated by the Ratio of Stroke Volume by End Systolic Volume at Month 12
timeFrame: Baseline, Month 12
measure: Change From Baseline in RV End-Diastolic Volume Index at Month 12
timeFrame: Baseline, Month 12
measure: Change From Baseline in RV Stroke Volume Index at Month 12
timeFrame: Baseline, Month 12
measure: Change From Baseline in 6MWD at Month 12, 24, and 36
timeFrame: Baseline, Months 12, 24, and 36
measure: 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
timeFrame: Baseline, Months 12, 24, and 36
measure: Change From Baseline in WHO FC at Months 12, 24, and 36
timeFrame: Baseline, Months 12, 24, and 36
measure: Change From Baseline in NT-proBNP at Months 12, 24, and 36
timeFrame: Baseline, Months 12, 24, and 36
measure: Change From Baseline in Borg Dyspnea Score at Months 12, 24, and 36
timeFrame: Baseline, Months 12, 24, and 36
measure: 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
timeFrame: Baseline, Months 12, 24, and 36
measure: Survival Rate: Number of Participants who Survived at Months 12, 24, and 36
timeFrame: Baseline to Months 12, 24, and 36
measure: Change From Baseline in mPAP at Months 24 and 36
timeFrame: Baseline, Months 24 and 36
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner University Medical Center (University of Arizona)
state: Arizona
city: Phoenix
country: United States
facility: HonorHealth John C. Lincoln Medical Center
state: Arizona
city: Fresno
country: United States
facility: University of California San Francisco - Fresno
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Pulmonary, Critical Care, Allergy and Sleep Medicine
state: California
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Tampa
country: United States
facility: USF
state: Florida
city: Austell
country: United States
facility: Georgia Clinical Research
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Health North Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Community Health Network
state: Indiana
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Integris Baptist Medical Center
state: Oklahoma
city: Tulsa
country: United States
facility: Oklahoma Heart Institute
state: Oklahoma
city: Philadelphia
country: United States
facility: Temple Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health
state: South Carolina
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Roanoke
country: United States
facility: Carilion Clinic
state: Virginia
Study officials:
References: