Pulmonary Hypertension: intensification and personalization of combination Rx (PHoenix): a phase IV randomized trial for the evaluation of dose-response and clinical efficacy of riociguat and selexipag using implanted technologies
Author(s)
Type
Journal Article
Abstract
Approved therapies for the treatment of patients with pulmonary arterial hypertension (PAH) mediate pulmonary vascular vasodilatation by targeting distinct biological pathways. International guidelines recommend that patients with an inadequate response to dual therapy with a phosphodiesterase type-5 inhibitor (PDE5i) and endothelin receptor antagonist (ERA), are recommended to either intensify oral therapy by adding a selective prostacyclin receptor (IP) agonist (selexipag), or switching from PDE5i to a soluble guanylate-cyclase stimulator (sGCS; riociguat). The clinical equipoise between these therapeutic choices provides the opportunity for evaluation of individualized therapeutic effects. Traditionally, invasive/hospital-based investigations are required to comprehensively assess disease severity and demonstrate treatment benefits. Regulatory-approved, minimally invasive monitors enable equivalent measurements to be obtained while patients are at home. In this 2 × 2 randomized crossover trial, patients with PAH established on guideline-recommended dual therapy and implanted with CardioMEMS™ (a wireless pulmonary artery sensor) and ConfirmRx™ (an insertable cardiac rhythm monitor), will receive ERA + sGCS, or PDEi + ERA + IP agonist. The study will evaluate clinical efficacy via established clinical investigations and remote monitoring technologies, with remote data relayed through regulatory-approved online clinical portals. The primary aim will be the change in right ventricular systolic volume measured by magnetic resonance imaging (MRI) from baseline to maximal tolerated dose with each therapy. Using data from MRI and other outcomes, including hemodynamics, physical activity, physiological measurements, quality of life, and side effect reporting, we will determine whether remote technology facilitates early evaluation of clinical efficacy, and investigate intra-patient efficacy of the two treatment approaches.
Date Issued
2024-01-01
Date Acceptance
2024-01-02
Citation
Pulmonary Circulation, 2024, 14 (1)
ISSN
2045-8932
Publisher
Wiley
Journal / Book Title
Pulmonary Circulation
Volume
14
Issue
1
Copyright Statement
© 2024 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/38500737
PII: PUL212337
Subjects
AMBRISENTAN
ARTERIAL-HYPERTENSION
Cardiac & Cardiovascular Systems
Cardiovascular System & Cardiology
CARE
DOUBLE-BLIND
Life Sciences & Biomedicine
LONG-TERM EXTENSION
MANAGEMENT
oral prostacyclin-receptor agonist
remote monitoring
Respiratory System
Science & Technology
soluble guanylate-cyclase stimulator
TADALAFIL
targeted therapy
THERAPY
Publication Status
Published
Coverage Spatial
United States
Article Number
e12337
Date Publish Online
2024-03-17