Pulmonary Arterial Hypertension - ARTISAN (Afterload Reduction To Improve Right Ventricular Structure And FuNction)

This is a phase 4, prospective, multicenter, single-arm, open-label study designed to evaluate the effect of early and rapid treprostinil therapy on mPAP reduction to improve RV function and reverse RV remodeling in patients with PAH. This study will use the CardioMEMS™ HF System (hereafter referred to as CardioMEMS) to measure and monitor mPAP, but may allow mPAP monitoring via RHC, if CardioMEMS is NOT available at a subject's Baseline Visit (Day 1) or if the CardioMEMS™ PA Sensor implantation is unsuccessful.

If CardioMEMS is NOT available, subjects will undergo RHC at the Baseline Visit (Day 1). A RHC to re-assess mPAP will be performed at Months 6, 12, 24, and 36. Subjects who begin the study using only RHC for mPAP measurement will continue to be evaluated via RHC for the remainder of the study.
If CardioMEMS is available, subjects will undergo RHC and implantation of a permanent CardioMEMS PA Sensor at the Baseline Visit (Day 1). CardioMEMS will be used to assess mPAP twice per week during the first 3 months of the study and weekly thereafter.

Weekly hemodynamic monitoring should continue until Month 12 and mPAP is ≤35 mmHg, the Investigator may then assess the subject's mPAP monthly for the remainder of the study.

However, if the CardioMEMS PA Sensor implantation is unsuccessful, subjects may be enrolled and evaluated using serial RHC, if written approval is obtained from the Sponsor's Medical Monitor. The subjects must meet all eligibility criteria, except Exclusion 17 (pulmonary artery branch diameter <7 mm). These subjects will follow the same procedures as noted above for those who are enrolled if CardioMEMS is NOT available.

Investigators will use mPAP data to guide medical therapy, dose titration, and assess eligibility to transition from parenteral to oral treprostinil. Treprostinil therapy (parenteral or oral) may continue, as tolerated, towards the goal of further reduction of mPAP until Month 36.

Criteria:

Inclusion Criteria:

  1. 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
  2. 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
  3. 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
  4. REVEAL Lite 2 risk score ≤9
  5. WHO FC II or III
  6. 6MWD >165 meters

Exclusion Criteria:

  1. PAH-related Exclusion Criteria:
  2. Prior or current use of epoprostenol, treprostinil, iloprost, beraprost, or selexipag
  3. Positive vasoreactivity test in idiopathic, heritable, or drug/toxin induced PAH
  4. Amphetamine use within the past 12 months
  5. WHO Groups 2, 3, 4, and 5
  6. Use of any other investigational drug, device, or therapy within 30 days of the Baseline visit
  7. Moderate or severe hepatic impairment (Child-Pugh Class B and C)
  8. 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)
  9. 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
  10. Permanent cardiac pacemaker or automatic internal cardioverter that would interfere with conduct of cMRI
  11. 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:

  1. Previously implanted with CardioMEMS pulmonary artery Sensor or unwilling/unable to permit collection and perform upload (transmission) of pulmonary artery pressure (PAP) readings
  2. 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.

Location: Hartford Hospital

Contact: Amer Abdullah, 860-972-1250, [email protected]

Sponsor: United Therapeutics