부산대학교 도서관

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.
Competing Interests: Dr Frances Varian: MRC clinical fellow, travel and conference funding from Janssen Ltd. Dr Jennifer Dick, Mr Christian Battersby, Mr Stefan Roman, Miss Jenna Ablott, Dr Lisa Watson, Mrs Sarah Bizmahfooz, and Dr Hamza Zafar: none declared. Dr Gerry Colgan: no direct conflicts, has undertaken consultancy work & honoraria for Janssen Ltd, Bayer Ltd, MSD. Received research funding from Janssen Ltd. Dr John Cannon: support to attend conferences from Janssen and been paid for advisory boards by Janssen and Ferrer. Jay Suntharalingam and Dr Jim Lordan: none declared. Professor Luke Howard: I have received honoraria for advisory boards, steering committees, and speaking from Janssen. My department has received research funding support from Janssen. I have received personal support for travel, accommodation, and registration at international meetings. I have received honoraria for advisory boards and speaking from MSD. I have received honoraria for advisory boards from Endotronix. Colm McCabe: none declared. Dr John Wort: I have received honoraria from Janssen, MSD, Ferrer, and Acceleron, research grants from Janssen and Ferrer and travel and accommodation grants from Janssen. Laura Price and Dr Colin Church: none declared. Dr Neil Hamilton: Honoraria from MSD and Janssen, travel and accommodation grants from Janssen, participation on advisory boards for Bayer, MSD, Janssen, and Vifor, and is a board member on the NHS Specialist respiratory clinical reference group. Dr Abdul Hameed: none declared. Dr Judith Hurdman, Dr Iain Armstrong and Dr Charlie Elliot: none declared. Prof Robin Condliffe: No COI. Received honoraria for speaking and advisory boards from Janssen and MS. Prof Martin Wilkins: support from NIHR for clinical research facility and biomedical research center infrastructure support BHF center support (RE/18/4/34215), consulting fees for MorphogenIX, Janssen and Janssen, Kinaset, Chiesi, Aerami, BenevolentAI, Novartis, and VIVS, participation on data safety monitoring board for Acceleron and GSK. Associate Professor Alastair Webb: none declared. Dr David Adlam: none declared. Professor Ray L Benza: steering and adjudication committees ABBOTT. Professor Kazem Rahimi: receives grants from the Oxford Martin School and the British Heart Foundation. He is an associate editor of Heart and a specialty editor of PLOS Medicine. And he is a cofounder of Zeesta and sits on the advisory board of Medtronic. Dr Moha Shojaei, Dr Nan Lin, Prof James Wason, Dr Alasdair McIntosh, Prof Alex McConnachie, and Dr Jennifer Middleton: none declared. Dr Roger Thompson: I have received honoraria, travel support, and grant funding from Janssen. Prof David Kiely: Support and grants received from NIHR Sheffield Biomedical Research Centre, Janssen Pharmaceuticals; additional grants from Ferrer; consulting fees, honoraria payments, and supports for attending meetings received from Janssen Pharmaceuticals, Ferrer, Altavant, MSD, and united Therapeutics, participants on advisory boards with Janssen and MSD; members of clinical reference group for specialist respiratory medicine (NHS England) and lead of UK national audit of pulmonary hypertension. Dr Mark Toshner: funding from NIHR Cambridge BRC, NIHR HTA; consulting fees from MorphogenIX and Jansen; participation on data safety monitoring board/advisory board with ComCov and FluCov. Dr Alex Rothman: research funding: Wellcome Trust Clinical Research Career Development Fellowship (206632/Z/17/Z), Medical Research Council (UK) Experimental Medicine Award (MR/W026279/1), NIHR Biomedical Research Center Sheffield, Contribution in kind: Medtronic, Abbott, Endotronix, Novartis, Janssen. Research support and consulting: NXT Biomedical, Endotronix, SoniVie, Neptune, Gradient.
(© 2024 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)