Varian, Frances and Dick, Jennifer and Battersby, Christian and Roman, Stefan and Ablott, Jenna and Watson, Lisa and Binmahfooz, Sarah and Zafar, Hamza and Colgan, Gerry and Cannon, John and Suntharalingam, Jay and Lordan, Jim and Howard, Luke and McCabe, Colm and Wort, John and Price, Laura and Church, Colin and Hamilton, Neil and Armstrong, Iain and Hameed, Abdul and Hurdman, Judith and Elliot, Charlie and Condliffe, Robin and Wilkins, Martin and Webb, Alastair and Adlam, David and Benza, Ray L. and Rahimi, Kazem and Shojaei‐Shahrokhabadi, Mohadeseh and Lin, Nan X. and Wason, James M. S. and McIntosh, Alasdair and McConnachie, Alex and Middleton, Jennifer T. and Thompson, Roger and Kiely, David G. and Toshner, Mark and Rothman, Alexander (2024) 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. Pulmonary Circulation, 14 (1): e12337. ISSN 2045-8932

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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.

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