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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)

Primary Purpose

Pulmonary Arterial Hypertension

Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Parenteral Treprostinil
Oral Treprostinil
Sponsored by
United Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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) ≥3 Wood units
    • Pulmonary artery wedge pressure (PAWP) ≤15 mmHg
  • Treatment naïve or on a stable dose of an endothelin receptor antagonist (ERA) and/or phosphodiesterase type 5 inhibitor (PDE-5i) for ≥30 days, but <6 months prior to the Baseline visit
  • 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 subject safety (for example, active infection, chronic thromboembolic pulmonary hypertension, or acute/recent deep vein thrombosis or pulmonary embolism)

cMRI-related Exclusion Criteria:

  • 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.

Sites / Locations

  • Banner University Medical Center (University of Arizona)Recruiting
  • HonorHealth John C. Lincoln Medical CenterRecruiting
  • University of California San Francisco - FresnoRecruiting
  • University of California San Francisco Pulmonary, Critical Care, Allergy and Sleep MedicineRecruiting
  • Hartford HospitalRecruiting
  • Piedmont Healthcare Pulmonary & Critical Care ResearchRecruiting
  • Northwestern Memorial HospitalRecruiting
  • Massachusetts General HospitalRecruiting
  • Henry Ford Health SystemRecruiting
  • University of Nebraska Medical CenterRecruiting
  • University of Rochester Medical CenterRecruiting
  • University of North Carolina at Chapel HillRecruiting
  • The Ohio State University Wexner Medical CenterRecruiting
  • Integris Baptist Medical CenterRecruiting
  • Prisma Health - UpstateRecruiting
  • UT Southwestern Medical CenterRecruiting
  • Carilion ClinicRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treprostinil

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Change From Baseline in mPAP at 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).
Change From Baseline in RV-Pulmonary Artery (PA) Coupling Estimated by the Ratio of Stroke Volume by End Systolic Volume at Month 12
Change From Baseline in RV End-Diastolic Volume Index at Month 12
Change From Baseline in RV Stroke Volume Index at Month 12
Change From Baseline in 6MWD at Month 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
Change From Baseline in WHO FC at Months 12, 24, and 36
Change From Baseline in NT-proBNP at Months 12, 24, and 36
Change From Baseline in Borg Dyspnea Score at 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
Survival Rate: Number of Participants who Survived at Months 12, 24, and 36
Change From Baseline in mPAP at Months 24 and 36

Full Information

First Posted
January 10, 2022
Last Updated
October 17, 2023
Sponsor
United Therapeutics
Collaborators
Lung Biotechnology PBC
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1. Study Identification

Unique Protocol Identification Number
NCT05203510
Brief Title
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
Acronym
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 10, 2022 (Actual)
Primary Completion Date
September 12, 2024 (Anticipated)
Study Completion Date
September 12, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
United Therapeutics
Collaborators
Lung Biotechnology PBC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treprostinil
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Parenteral Treprostinil
Other Intervention Name(s)
Remodulin
Intervention Description
Parenteral treprostinil will be administered per schedule specified in the arm description.
Intervention Type
Drug
Intervention Name(s)
Oral Treprostinil
Other Intervention Name(s)
Orenitram
Intervention Description
Oral treprostinil will be administered per schedule specified in the arm description.
Primary Outcome Measure Information:
Title
Change From Baseline in Right Ventricular Ejection Fraction (RVEF), as Measured by Cardiac Magnetic Resonance Imaging (cMRI) at Month 12
Time Frame
Baseline, Month 12
Secondary Outcome Measure Information:
Title
Change From Baseline in mPAP at Month 12
Time Frame
Baseline, Month 12
Title
Number of Participants With Clinical Improvement From Baseline to Month 12, 24, and 36
Description
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).
Time Frame
Baseline to Months 12, 24, and 36
Title
Change From Baseline in RV-Pulmonary Artery (PA) Coupling Estimated by the Ratio of Stroke Volume by End Systolic Volume at Month 12
Time Frame
Baseline, Month 12
Title
Change From Baseline in RV End-Diastolic Volume Index at Month 12
Time Frame
Baseline, Month 12
Title
Change From Baseline in RV Stroke Volume Index at Month 12
Time Frame
Baseline, Month 12
Title
Change From Baseline in 6MWD at Month 12, 24, and 36
Time Frame
Baseline, Months 12, 24, and 36
Title
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
Time Frame
Baseline, Months 12, 24, and 36
Title
Change From Baseline in WHO FC at Months 12, 24, and 36
Time Frame
Baseline, Months 12, 24, and 36
Title
Change From Baseline in NT-proBNP at Months 12, 24, and 36
Time Frame
Baseline, Months 12, 24, and 36
Title
Change From Baseline in Borg Dyspnea Score at Months 12, 24, and 36
Time Frame
Baseline, Months 12, 24, and 36
Title
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
Time Frame
Baseline, Months 12, 24, and 36
Title
Survival Rate: Number of Participants who Survived at Months 12, 24, and 36
Time Frame
Baseline to Months 12, 24, and 36
Title
Change From Baseline in mPAP at Months 24 and 36
Time Frame
Baseline, Months 24 and 36

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mary Lou Tomson
Phone
240-821-1881
Email
artisan@lungbiotechnology.com
Facility Information:
Facility Name
Banner University Medical Center (University of Arizona)
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Franz Rischard
Facility Name
HonorHealth John C. Lincoln Medical Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85020
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Therese Sargent
Facility Name
University of California San Francisco - Fresno
City
Fresno
State/Province
California
ZIP/Postal Code
93701
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sorour Almasri
Facility Name
University of California San Francisco Pulmonary, Critical Care, Allergy and Sleep Medicine
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marc Simon
Facility Name
Hartford Hospital
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06106
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Raj Parikh
Facility Name
Piedmont Healthcare Pulmonary & Critical Care Research
City
Austell
State/Province
Georgia
ZIP/Postal Code
30106
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chad Miller
Facility Name
Northwestern Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ruben Mylvaganam
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aaron Waxman
Facility Name
Henry Ford Health System
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gillian Grafton
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ronald Zolty, MD
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14623
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniel Lachant
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hubert James Ford III
Facility Name
The Ohio State University Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Scott Visovatti
Facility Name
Integris Baptist Medical Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Kingrey
Facility Name
Prisma Health - Upstate
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jason Guichard
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kelly Chin
Facility Name
Carilion Clinic
City
Roanoke
State/Province
Virginia
ZIP/Postal Code
24014
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Moises Cossio

12. IPD Sharing Statement

Learn more about this trial

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

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